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EXPLORATIONS: AN OPEN INVITATION TO BIOLOGICAL ANTHROPOLOGY
Editors: Beth Shook, Katie Nelson, Kelsie Aguilera and Lara Braff
American Anthropological Association Arlington, VA
2019
CC BY-NC 4.0 International, except where otherwise noted
ISBN – 978-1-931303-63-7
www.explorations.americananthro.org
Hayley Mann, M.A., Binghamton University Xazmin Lowman, Ph.D.,
University of California, Irvine Malaina Gaddis, Ph.D.
Learning Objectives
* Define terms useful to molecular biology and genetics.
* Explain and identify the purpose of both DNA replication and the
cell cycle.
* Identify key differences between mitosis and meiosis.
* Outline the process of protein synthesis including transcription and
translation.
* Use principles of Mendelian inheritance to predict genotypes and
phenotypes of future generations.
* Explain complexities surrounding patterns of genetic inheritance and
polygenic traits.
* Discuss challenges to and bioethical concerns of genetic testing.
I [Hayley Mann] started my Bachelor’s degree in 2003, which was the same
year the Human Genome Project released its first draft sequence. I
initially declared a genetics major because I thought it sounded cool.
However, upon taking an actual class, I discovered that genetics was
challenging. In addition to my genetics major, I signed up for
biological anthropology classes and soon learned that anthropology could
bring all those molecular lessons to life. For instance, we are composed
of cells, proteins, nucleic acids, carbohydrates, and lipids.
Anthropologists often include these molecules in their studies to
identify how humans vary; if there are meaningful differences, they
propose theories to explain them.
Since the release of the first human genome sequence, the field of
genetics has grown into genomics. Researchers now address these complex
questions on a large scale. To process “big data,” some scientists have
moved to working on a computer full time doing computational biology. As
you learned in Chapter 1, molecular anthropologists use genetics to
compare ancient and modern populations as well as study nonhuman
primates. Molecular anthropologists must also stay current with
advancing technology you will learn about the results of some of this
genomic research as it has been applied to fossils in Chapters 11 and
12). If you wish to be part of this dynamic field, then take advantage
of available campus laboratory classes and internships and also never
stop reading scientific papers.
This chapter provides the basics for understanding human variation and
how the evolutionary process works. A few advanced genetics topics are
also presented because biotechnology is now commonplace in health and
society. Understanding the science behind this remarkable field means
you will be able to participate in bioethical and anthropological
discussions as well as make more informed decisions regarding genetic
testing.
CELLS AND MOLECULES
Molecules of Life
Figure 3.1
Probably the most familiar nucleic acid is deoxyribonucleic acid (DNA).
DNA comprises a sugar phosphate backbone and nucleotides Figure 3.2).
More details on the physical structure of DNA and what information DNA
nucleotides provide will be discussed later.) Anthropologists can
analyze sequences of DNA nucleotides and determine how different
organisms are related to each other, since they all have their own
unique DNA genetic code. In the case of humans, forensic scientists can
identify individuals by analyzing 20 different short DNA sequences known
as “CODIS Core Loci.” Another nucleic acid is called ribonucleic acid
(RNA). One type of RNA molecule is responsible for chaining amino acids
together in order to build proteins Figure 3.3 and Figure 3.4). How RNA
synthesizes amino acids into proteins will be reviewed further on in the
chapter.
Organisms are composed of four basic types of molecules that are
essential for cell structure and function: proteins, lipids,
carbohydrates, and nucleic acids. Proteins are strings of amino acids
that are often folded into complex 3-D shapes. The structure of lipids
can be described as having a hydrophilic water-loving) head and a
hydrophobic water-repelling) tail Figure 3.1). When lipids are chained
together, they form more-complex molecules called fats and
triglycerides. Carbohydrates are composed of carbon and hydrogen atoms
that can be broken down to supply energy for an organism. Lastly,
nucleic acids carry genetic information about a living organism.
Figure 3.2
Figure 3.3
Figure 3.4
Cells
In 1665, Robert Hooke observed slices of plant cork using a microscope.
Hooke noted that the microscopic plant structures he saw resembled
cella, meaning “a small room” in Latin. Approximately two centuries
later, biologists recognized the cell as being the most fundamental unit
of life and that all life is composed of cells. Cellular organisms can
be characterized as two main cell types: prokaryotes and eukaryotes.
Figure 3.5
Prokaryotes include bacteria and archaea, and they are composed of a
single cell. Additionally, their DNA and organelles are not surrounded
by individual membranes. Thus, no compartments separate their DNA from
the rest of the cell Figure 3.5). It is well known that some bacteria
can cause illness in humans. For instance, Escherichia coli E. coli) and
Salmonella contamination can result in food poisoning symptoms.
Pneumonia and strep throat are caused by Streptococcal bacteria.
Neisseria gonorrhoeae is a bacterial sexually transmitted disease.
Although bacteria are commonly associated with illness, not all bacteria
are harmful. For example, researchers are studying the relationship
between the microbiome and human health. The bacteria that are part of
the healthy human microbiome perform beneficial roles, such as food
digestion, boosting the immune system, and even making vitamins e.g.,
B12 and K).
Archaea, the other type of prokaryotic organism, were once believed to
be closely related to bacteria. However, it was determined through
genetic analysis that archaea have their own distinct evolutionary
lineage so biologists reclassified them into their own taxonomic domain.
Archaea were discovered living in extreme environments and are therefore
known as “extremophiles.” For example, archaea can be found in high
temperatures, such as Old Faithful Geyser in Yellowstone National Park.
Eukaryotes can be single-celled or multicelled in their body
composition. In contrast to prokaryotes, eukaryotes possess membranes
that surround their DNA and organelles. An example of a single-celled
eukaryote is the microscopic algae found in ponds phytoplankton), which
can produce oxygen from the sun. Yeasts are also single celled, and
fungi can be single- or multicellular. Plants and animals are all
multicellular. Although plant and animal cells have a surprising number
of similarities, there are some key differences. For example, plant
cells possess a thick outer cell membrane made of a fibrous carbohydrate
called cellulose Figure 3.6). Animal and plant cells also have different
tissues. A tissue is an aggregation of cells that are morphologically
similar and perform the same task. For most plants, the outermost layer
of cells forms a waxy cuticle that helps to protect the cells and to
prevent water loss. However, humans have skin, the outermost cell layer
of which is mostly composed of a tough protein called keratin. Overall,
humans have a diversity of tissue types e.g., cartilage, brain, and heart).
Animal Cell Organelles
Figure 3.6
Figure 3.7
An animal cell is surrounded by a double membrane called the
phospholipid bilayer Figure 3.7). A closer look reveals that this
protective barrier is made of lipids and proteins that provide structure
and function for cellular activities. For example, lipids and proteins
embedded in the cell’s membrane work together to regulate the passage of
molecules and ions e.g., H2O and sodium) into and out of the cell.
Cytoplasm is the jelly-like matrix inside of the cell membrane. Part of
the cytoplasm comprises organelles, which perform different specialized
tasks for the cell Figure 3.8). An example of an organelle is the
nucleus, where the cell’s DNA is located Figure 3.9). The double
membrane that encloses the nucleus is known as the nuclear envelope; its
purpose is to regulate molecules into and out of the nucleus and serve
as a barrier to protect DNA integrity.
Figure 3.8
Figure 3.9
Another important organelle is the mitochondrion Figure 3.10).
Mitochondria are often referred to as “powerhouse centers” because they
produce energy for the cell in the form of adenosine triphosphate (ATP).
Depending on the species and tissue type, multicellular eukaryotes can
have hundreds to thousands of mitochondria in each of their cells.
Scientists have determined that mitochondria played an important role in
the evolution of the eukaryotic cell. Mitochondria were once symbiotic
prokaryotic organisms i.e., helpful bacteria) that transformed into
cellular organelles over time. Because mitochondria used to be separate
organisms, this explains why mitochondria also have their own DNA,
called mitochondrial DNA (mtDNA). All organelles have important
physiological functions, and when they cannot perform their role
optimally, it can result in disease. For example, there are
mitochondrial diseases for which cells have abnormally less
mitochondria. In humans, this leads to various neurological symptoms and
disorders. Figure 3.11 lists other organelles found in the cell and
their specialized cellular roles.
Figure 3.10
Cell structure Description
Cytoplasm Fluid substance located inside of cell membrane that contains
organelles
Nucleopore Pores in the nuclear envelope that are selectively permeable
Nucleus Contains the cell’s DNA and is surrounded by the nuclear envelope
Nucleolus Resides inside of the nucleus and is the site of ribosomal
RNA rRNA) transcription, processing, and assembly
Mitochondrion Responsible for cellular respiration, where energy is
produced by converting nutrients into ATP
Ribosome Located in the cytoplasm and also the membrane of the rough
endoplasmic reticulum. Messenger RNA mRNA) binds to ribosomes and
proteins are synthesized
Endoplasmic reticulum ER) Continuous membrane with the nucleus that
helps transport, synthesize, modify, and fold proteins. Rough ER has
embedded ribosomes, whereas smooth ER lacks ribosomes
Golgi body Layers of flattened sacs that receive and transmit messages
from the ER to secrete and transport proteins within the cell
Lysosome Located in the cytoplasm and contains enzymes to degrade
cellular components
Microtubule Involved with cellular movement including intracellular
transport and cell division
Centrioles Assist with the organization of mitotic spindles which
extend and contract for the purpose of cellular movement during mitosis
and meiosis
Figure 3.11 Names of organelles and their cellular functions.
INTRODUCTION TO GENETICS
Genetics is the study of heredity. Parents pass down their genetic
traits to their offspring. Although children resemble their parents,
traits often vary in appearance or molecular function. For example, two
parents with normal color vision can sometimes produce a son with red-
green colorblindness. Patterns of genetic inheritance will be discussed
in a later section. Molecular geneticists study the biological
mechanisms responsible for creating variation between individuals, such
as DNA mutations see Chapter 4), cell division, and genetic regulation.
Molecular anthropologists use genetic data to test anthropological
questions. Although their interests are diverse, areas of molecular
anthropology research include the following: human origins, dispersals,
evolution, adaptation, demography, health, disease, behavior, and animal
domestication. In addition to conducting research in a laboratory,
molecular anthropologists also work in the field with different
communities of people. Some anthropologists also study DNA from
individuals who have been deceased for decades—even hundreds or
thousands of years. The study of ancient DNA (aDNA) has led to the
development of specialized laboratory techniques. Over time, the DNA in
skeletons of ancient individuals becomes degraded i.e., less intact),
which is why careful methodological considerations must be taken. A
recent example of an aDNA study is provided in Special Topic: Native
American Immunity and European Diseases, and another will be presented
in Chapter 10.
SPECIAL TOPIC: FOCUS ON NATIVE AMERICAN IMMUNITY AND EUROPEAN DISEASES
—A STUDY OF ANCIENT DNA
Figure 3.12a
Beginning in the early 15th century, Native Americans progressively
suffered from high mortality rates as the result of colonization from
foreign powers. European-borne diseases such as measles, tuberculosis,
influenza, and smallpox are largely responsible for the population
collapse of indigenous peoples in the Americas. Many Europeans who
immigrated to the New World had lived in large sedentary populations,
which also included coexisting with domestic animals and pests. Although
a few prehistoric Native American populations can be characterized as
large agricultural societies especially in Mesoamerica), their overall
culture, community lifestyle, and subsistence practices were markedly
different from that of Europeans. Therefore, because they did not share
the same urban living environments as Europeans, it is believed that
Native Americans were susceptible to old-world diseases.
In 2016, a Nature article published by John Lindo and colleagues was the
first to investigate whether pre contact Native Americans possessed a
genetic susceptibility to European diseases. Their study included
Tsimshians, a First Nation community from British Columbia Figure 3.12).
The DNA from both present-day and ancient individuals who lived between
500 and 6,000 years ago) was analyzed. The research team discovered that
a change occurred in the genetic region HLADQ-1, which is a member of
the major histocompatibility complex MHC) immune system molecules. These
molecules are responsible for detecting and triggering an immune
response against pathogens. Lindo and colleagues 2016) concluded that
HLADQ-1 helped Native Americans adapt to their local environmental
ecology. However, when European-borne epidemics occurred in the
Northwest during the 1800s, a certain HLADQ-1 DNA sequence associated
with ancient Tsimshian immunity was no longer adaptive. As the result of
past selective pressures from European diseases, present-day Tsimshians
have a different frequency of HLADQ-1 sequences. The precise role that
HLADQ-1 plays in immune adaptation still requires further investigation.
But overall, this study serves as an example of how studying ancient DNA
from the remains of deceased individuals can help provide insight into
living human populations and historical events.
Figure 3.12b
DNA Carries Hereditary Information
Surprisingly, the study of inheritance preceded the discovery of DNA.
For a period of time, it was believed that proteins carried the
hereditary information passed from parents to offspring. Then, in 1944,
Oswald Avery, Colin MacLeod, and Maclyn McCarty discovered an
association between extracted nucleic acids and the success of their
bacterial genetic experiments. Specifically, they demonstrated that DNA
was the molecule responsible for the genetic transformation of their
pneumonia bacterial strains. Although this was revolutionary work at the
time, the field of molecular biology did not fully embrace their
findings it has also been suggested that they were overlooked for a
Nobel Prize). It was eventually accepted by the scientific community
that DNA is the hereditary material of an organism, especially after the
chemical structure of DNA was revealed.
DNA Structure
The 1953 discovery of the molecular structure of DNA was one of the
greatest scientific achievements of all time. Using X-ray
crystallography, Rosalind Franklin Figure 3.13) provided the image that
clearly showed the double helix shape of DNA. However, due to a great
deal of controversy, Franklin’s colleague and outside associates
received greater publicity for the discovery. In 1962, James Watson,
Francis Crick, and Maurice Wilkins received a Nobel Prize for developing
a biochemical model of DNA. Unfortunately, Rosalind Franklin had passed
away in 1958 from ovarian cancer. In current times, Franklin’s important
contribution and her reputation as a skilled scientist are widely
acknowledged.
The double helix shape of DNA can be described as a twisted ladder refer
back to Figure 3.2). More specifically, DNA is a double stranded
molecule with its two strands oriented in opposite directions i.e.,
antiparallel). Each strand is composed of nucleotides with a sugar
phosphate backbone. There are four different types of DNA nucleotides:
adenine A), thymine T), cytosine C), and guanine G). The two DNA strands
are held together by nucleotide base pairs, which have chemical bonding
rules. The complementary base-pairing rules are as follows: A and T bond
with each other, while C and G form a bond. The chemical bonds between A
—T and C—G are formed by “weak” hydrogen atom interactions, which means
the two strands can be easily separated. A DNA sequence is the order of
nucleotide bases A, T, G, C) along only one DNA strand. If one DNA
strand has the sequence CATGCT, then the other strand will have a
complementary sequence GTACGA. This is an example of a short DNA
sequence. In reality, there are approximately three billion DNA base
pairs in human cells.
DNA Is Highly Organized Within the Nucleus
Figure 3.13
If you removed the DNA from a single human cell and stretched it out
completely, it would measure approximately two meters about 6.5 feet).
Therefore, DNA molecules must be compactly organized in the nucleus. To
achieve this, the double helix configuration of DNA undergoes coiling.
An analogy would be twisting a string until coils are formed and then
continuing to twist so that secondary coils are formed, and so on. To
assist with coiling, DNA is first wrapped around proteins called
histones. This creates a complex called chromatin, which resembles
“beads on a string” Figure 3.14). Next, chromatin is further coiled into
a chromosome. Another important feature of DNA is that chromosomes can
be altered from tightly coiled chromatin) to loosely coiled
euchromatin). Most of the time, chromosomes in the nucleus remain in a
euchromatin state so that DNA sequences are accessible for regulatory
processes to occur.
Figure 3.14
Human body cells typically have 23 pairs of chromosomes, for a total of
46 chromosomes in each cell’s nucleus Figure 3.15). An interesting fact
is that the number of chromosomes an organism possesses varies, and this
figure is not dependent upon the size or complexity of the organism. For
instance, chimpanzees have a total of 48 chromosomes, while hermit crabs
have 254. Chromosomes also have a distinct physical structure, including
centromeres the “centers”) and telomeres the ends) Figure 3.16). Because
of centromeres, chromosomes are described as having two different
“arms,” where one arm is long and the other is shorter. Centromeres play
an important role during cell division, which will be discussed in the
next section. Telomeres are located at the ends of chromosomes and they
help protect the chromosomes from degradation after every round of cell
division. However, our telomeres become shorter as we age, and if
chromosome telomeres become too short, then the cell will stop dividing.
Therefore, the link between the regulation of telomere length and
cellular aging is of great interest to researchers.
Figure 3.15
Figure 3.16
REPLICATION AND CELL DIVISION
DNA
For life to continue and flourish, cells must be able to divide. Tissue
growth and cellular damage repair are also necessary to maintain an
organism throughout its life. All these rely on the dynamic processes of
DNA replication and the cell cycle. The mechanisms highlighted in this
section are tightly regulated and represent only part of the life cycle
of a cell.
DNA Replication
DNA replication is the process by which new DNA is copied from an
original DNA template. It is one phase of the highly coordinated cell
cycle and requires a variety of enzymes with special functions.
Specifically, enzymes carry out the structural and high-energy reactions
associated with replicating a double helical molecule. The creation of a
complementary DNA strand from a template strand is described as semi-
conservative replication. The result of semi conservative replication is
two separate double-stranded DNA molecules, each of which is composed of
an original “parent” template strand and a newly synthesized “daughter”
DNA strand.
DNA replication progresses in three steps referred to as initiation,
elongation, and termination. Initiation denotes the start of DNA
replication by recruiting enzymes to specific sites along the DNA
sequence. For example, the double helix of DNA presents structural
challenges for replication, so an initiator enzyme, called helicase,
“unwinds” DNA by breaking the hydrogen bonds between the two parent
strands. The unraveling of the helix into two separated strands creates
a fork, which is the active site of replication machinery Figure 3.17).
Once both strands are separated, the parent template strands are
exposed, meaning they can be read and replicated.
Figure 3.17
Elongation describes the assembly of new DNA daughter strands from
parent strands. The two parent strands can further be classified as
leading strand or lagging strand and are distinguished by the continuous
or discontinuous direction of replication, respectively. A short
fragment of RNA nucleotides acts as a primer, which binds to the parent
DNA strand that will be copied. The leading strand receives one primer
and the lagging strand receives several. Elongation proceeds with help
from enzymes called DNA polymerases, which read parent template strands
in a specific direction. Complementary nucleotides are added, and the
newly formed daughter strand will grow. The direction in which
replication proceeds depends on whether it is the leading or lagging
strand. On the leading parent strand, a DNA polymerase will create one
continuous strand. Because the lagging parent strand requires several
primers, disjointed strands called Okazaki fragments) will be generated.
Other enzymes will fill in the missing nucleotide gaps between the
disconnected lagging strand Okazaki fragments.
Finally, termination refers to the end of DNA replication activity. It
is signaled by a stop sequence in the DNA, which is recognized by
machinery at the replication fork. The end result of DNA replication is
that the number of chromosomes are doubled so that the cell can divide
into two.
DNA Mutations
DNA replication should result in the creation of two molecules with
identical DNA nucleotide sequences. Although DNA polymerases are quite
precise during DNA replication, copying mistakes are estimated to occur
every 107 DNA
nucleotides. Variation from the original DNA sequence is known as a
mutation. The different types of mutations will be discussed in greater
detail in Chapter 4. Briefly, mutations can result in single nucleotide
changes as well as the insertion or deletion of nucleotides and repeated
sequences. Depending on where they occur, mutations can be deleterious
harmful). For example, mutations may occur in regions that control cell
cycle regulation, which can result in cancer see Special Topic: The Cell
Cycle and Immortality of Cancer Cells). Many other mutations, however,
are not harmful to an organism.
Regardless of their effect, the cell attempts to reduce the frequency of
mutations that occur during DNA replication.
To accomplish this, there are polymerases with proofreading capacities
that can identify and correct mismatched nucleotides. These safeguards
reduce the frequency of DNA mutations so that they only occur every 109
nucleotides.
SPECIAL TOPIC: THE CELL CYCLE AND IMMORTALITY OF CANCER CELLS
DNA replication is part of a series of preparatory phases that a cell
undergoes prior to cell division, collectively known as interphase
Figure 3.18). During interphase, the cell not only doubles its
chromosomes through DNA replication, but it also increases its metabolic
capacity to provide energy for growth and division. Transition into each
phase of the cell cycle is tightly controlled by proteins that serve as
checkpoints. If a cell fails to pass a checkpoint, then DNA replication
and/or cell division will not continue. Some of the reasons why a cell
may fail at a checkpoint is DNA damage, lack of nutrients to continue
the process, or insufficient size. In turn, a cell may undergo
apoptosis, which is a mechanism for cell death.
Figure 3.18
Unchecked cellular growth is a distinguishing hallmark of cancer. In
other words, as cancer cells grow and proliferate, they acquire the
capacity to avoid death and replicate indefinitely. This uncontrolled
and continuous cell division is also known as “immortality.” As
previously discussed, most cells lose the ability to divide due to
shortening of telomeres on the ends of chromosomes over time. One way in
which cancer cells retain replicative immortality is that the length of
their telomeres is continuously protected. Chemotherapy is often used to
treat cancer by targeting cell division, which halts the propagation of
genetically abnormal
cells. Another therapeutic approach that continues to be investigated is
targeting telomere activity to stop the division of cancer cells.
Researchers have exploited the immortality of cancer cells for molecular
research. The oldest immortal cell line is HeLa cells Figure 3.19),
which was harvested from Henrietta Lacks, an African-American woman
diagnosed with cervical cancer in 1955. At that time, extracted cells
frequently died during experiments, but surprisingly, HeLa cells
continued to replicate. Propagation of Lacks’s cell line has
significantly contributed to medical research, including ongoing cancer
research and helping to test the polio vaccine in the 1950s.
Unfortunately, Lacks had not given her consent for her tumor biopsy to
be used in cell culture research. Moreover, her family was unaware of
the extraction and remarkable application of her cells for two decades.
The history of HeLa cell origin was first revealed in 1976. The
controversy voiced by the Lacks family was included in an extensive
account of HeLa cells published in Rebecca Skloot’s 2010 book, The
Immortal Life of Henrietta Lacks. A film based on the book was also
released in 2017.
Figure 3.19
Mitotic Cell Division
The body and its various tissues are comprised of somatic cells.
Organisms that contain two sets of chromosomes in their somatic cells
are called diploid organisms. Humans have 46 chromosomes and they are
diploid because they inherit one set of chromosomes n = 23) from each
parent. As a result, they have 23 matching pairs of chromosomes, which
are known as homologous chromosomes. These homologous pairs vary in size
and are generally numbered from largest chromosome 1) to smallest
chromosome 22), as seen in Figure 3.15, with the exception of the 23rd
pair, which is made up of the sex chromosomes X and Y). Typically, the
female sex is XX and the male sex is XY. Individuals inherit an X
chromosome from their mother and an X or Y from their father.
In order to grow and repair tissues, somatic cells must divide. As
discussed previously, a cell must first replicate its genetic material
for cell division to occur. During DNA replication, each chromosome
produces double the amount of genetic information. The duplicated arms
of chromosomes are known as sister chromatids, and they are attached at
the centromeric region. To elaborate, the number of chromosomes stays
the same n = 46); however, the amount of genetic material is doubled in
the cell as the result of replication.
Mitosis is the process of somatic cell division that gives rise to two
diploid daughter cells. Figure 3.20 shows a brief overview of mitosis.
Once DNA and other organelles in the cell have finished replication,
mitotic spindle fibers microtubules) assist with chromosomal movement by
attaching to the centromeric region of each chromosome. Specifically,
the spindle fibers physically align each chromosome at the center of the
cell. Next, the spindle fibers divide the sister chromatids and move
each one to opposite sides of the cell. At this phase, there are 46
chromosomes on each side of the cell. The cell can now divide into two
fully separated daughter cells.
Figure 3.20
Meiotic Cell Division
Gametogenesis is the production of gametes sperm and egg cells); it
involves two rounds of cell division called meiosis. Similar to mitosis,
the parent cell in meiosis is diploid. However, meiosis has a few key
differences, including the number of daughter cells produced four cells,
which require two rounds of cell division to produce) and the number of
chromosomes each daughter cell has Figure 3.21). During the first round
of division known as meiosis I), each chromosome n = 46) replicates its
DNA so that sister chromatids are formed. Next, with the help of spindle
fibers, homologous chromosomes align near the center of the cell and
sister chromatids physically swap genetic material. In other words, the
sister chromatids of matching chromosomes cross over with each other at
matching DNA nucleotide positions. The occurrence of homologous
chromosomes crossing over, swapping DNA, and then rejoining segments is
called genetic recombination. The “genetic shuffling” that occurs in
gametes increases organismal genetic diversity by creating new
combinations of genes on chromosomes that are different from the parent
cell. Genetic mutations can also arise during recombination. For
example, there may be an unequal swapping of genetic material that
occurs between the two sister chromatids, which can result in deletions
or duplications of DNA nucleotides. Once genetic recombination is
complete, homologous chromosomes are separated and two daughter cells
are formed.
The daughter cells after the first round of meiosis are haploid, meaning
they only have one set of chromosomes n = 23). During the second round
of cell division known as meiosis II), sister chromatids are separated
and two additional haploid daughter cells are formed. Therefore, the
four resulting daughter cells have one set of chromosomes n = 23), and
they also have a genetic composition that is not identical to the parent
cells nor to each other.
Figure 3.21
Although both sperm and egg gamete production undergo meiosis, they
differ in the final number of viable daughter cells. In the case of
spermatogenesis, four mature sperm cells are produced. Although four egg
cells are also produced in oogenesis, only one of these egg cells will
result in an ovum mature egg). During fertilization, an egg cell and
sperm cell fuse, which creates a diploid cell that develops into an
embryo. The ovum also provides the cellular organelles necessary for
embryonic cell division. This includes mitochondria, which is why
humans, and most other multicellular eukaryotes, have the same mtDNA
sequence as their mothers.
Chromosomal Disorders
During mitosis or meiosis, entire deletions or duplications of
chromosomes can occur due to error. For example, homologous chromosomes
may fail to separate properly, so one daughter cell may end up with an
extra chromosome while the other daughter cell has one less. Cells with
an unexpected or abnormal) number of chromosomes are known as aneuploid.
Adult or embryonic cells can be tested for chromosome number
karyotyping). Aneuploid cells are typically detrimental to a dividing
cell or developing embryo, which can lead to a loss of pregnancy.
However, the occurrence of individuals being born with three copies of
the 21st chromosome is relatively common; this genetic condition is
known as Down Syndrome. Moreover, human males and females can be born
with aneuploid sex chromosome conditions such as XXY, XXX, and XO
referring to only one X chromosome).
PROTEIN SYNTHESIS
At the beginning of the chapter, we defined proteins as strings of amino
acids that fold into complex 3-D shapes. There are 20 standard amino
acids that can be strung together in different orders in humans, and the
result is that proteins can perform an impressive amount of different
functions. For instance, muscle fibers are proteins that help facilitate
movement. A special class of proteins immunoglobulins) help protect the
organism by detecting disease-causing pathogens in the body. Protein
hormones, such as insulin, help regulate physiological activity. Blood
hemoglobin is a protein that transports oxygen throughout the body.
Enzymes are also proteins, and they are catalysts for biochemical
reactions that occur in the cell e.g., metabolism). Larger-scale protein
structures can be visibly seen as physical features of an organism e.g.,
hair and nails).
Transcription and Translation
Coding nucleotides in our DNA provide instructions on how to make
proteins. Making proteins, also known as protein synthesis, can be
broken down into two main steps referred to as transcription and
translation. Protein synthesis relies on many molecules in the cell
including different types of regulatory proteins and RNAs for each step
in the process. Although there are many different types of RNA molecules
that have a variety of functions within the cell, we will mainly focus
on messenger RNA (mRNA).
A gene is a segment of DNA that codes for RNA, and genes can vary in
length from a few hundred to as many as two million base pairs in
length. The purpose of transcription is to make an RNA copy of that
genetic code Figure 3.22). Unlike double-stranded DNA, RNA molecules are
single-stranded nucleotide sequences refer back to Figure 3.2).
Additionally, while DNA contains the nucleotide thymine T), RNA does not
—instead, its fourth nucleotide is uracil U). Uracil is complementary to
or can pair with) adenine A), while cytosine C) and guanine G) continue
to be
complementary to each other. For transcription to proceed, a gene must
first be turned “on” by the cell see Special Topic: Genetic Regulation
of the Lactase LCT) Gene for a more detailed discussion of gene
regulation). The double stranded DNA is then separated, and one side of
the DNA strand is used as a template where complementary RNA nucleotides
are strung together. For example, if a DNA template is TACGGATGC, then
the newly constructed mRNA sequence will be AUGCCUACG. Sometimes the end
product needed by the cell is that transcribed RNA, but for protein
synthesis constructing the RNA specifically pre-messenger RNA, or pre-
mRNA) is just the first step.
Figure 3.22
Genes contain segments called introns and exons. Exons are considered
“coding” while introns are considered “noncoding”—meaning the
information they contain will not be needed to construct proteins. When
a gene is first transcribed into pre-mRNA, introns and exons are both
included Figure 3.23). However, once transcription is finished, introns
are removed in a process called splicing. During splicing, a protein/RNA
complex attaches itself to the pre mRNA and removes introns and then
connects the remaining exons, thus creating a shorter mature mRNA.
Figure 3.23
The process by which mRNA is “read” and amino acids chained together to
form new proteins is called translation. During translation, mature mRNA
is transported outside of the nucleus where it is bound to a ribosome
Figure 3.24). The nucleotides in the mRNA are read as triplets, which
are called codons. Each codon corresponds to an amino acid, and this is
the basis for building a protein. Continuing with our example from
above, the mRNA sequence AUG-CCU ACG codes for three amino acids. Using
a codon table Figure 3.25), AUG is a codon for methionine Met), CCU is
proline Pro), and ACG is threonine Thr). Therefore, the protein sequence
is Met-Pro-Thr. Methionine is the most common “start codon” AUG) for the
initiation of protein translation in eukaryotes. As the ribosome moves
along the mRNA, the growing amino acid chain exits the ribosome and
folds into a protein Figure 3.26). When the ribosome reaches a “stop”
codon UAA, UAG, or UGA), the ribosome stops adding new amino acids,
detaches from the mRNA, and the protein is released. Folded proteins can
then be used to complete a structural or functional task.
Figure 3.24
Figure 3.25
Figure 3.26
SPECIAL TOPIC: GENETIC REGULATION OF THE LACTASE (LCT) GENE
The LCT gene codes for a protein called lactase, an enzyme produced in
the small intestine. It is responsible for breaking down the sugar
“lactose” found in milk. Lactose intolerance occurs when not enough
lactase enzyme is produced and, in turn, digestive symptoms occur. To
avoid this discomfort, individuals may take lactase supplements, drink
lactose-free milk, or avoid milk products altogether.
The LCT gene is a good example of how cells regulate protein synthesis.
The promoter region of the LCT gene helps regulate whether it is
transcribed or not transcribed i.e., turned “on” or “off,”
respectively). Lactase production is initiated when a regulatory protein
known as a transcription factor binds to a site on the LCT promoter. RNA
polymerases are then recruited; they read DNA and string together
nucleotides to make RNA molecules Figure 3.22). An LCT pre-mRNA is
synthesized made) in the nucleus, and further chemical modifications
flank the ends of the mRNA to ensure the molecule will not be degraded
in the cell. Next, RNA processing occurs. A spliceosome complex removes
the introns and connects exons to form the mature mRNA. Once the LCT
mRNA is transported outside of the nucleus, it is bound to a ribosome,
which is a multi-protein complex that includes ribosomal RNA (rRNA). The
ribosome of eukaryotes has two main subunits: the smaller bottom subunit
that binds to the mRNA and the larger top subunit that contains transfer
RNA (tRNA) binding sites see Figure 3.24). Each tRNA has a nucleotide
anticodon that recognizes an mRNA codon. When a tRNA binds to an mRNA
codon in the ribosome, the tRNA transfers the corresponding amino acid.
rRNA ensures the newly added amino acid is linked in the correct order.
The growing protein then folds into the lactase enzyme, which can break
down lactose. Most animals lose their ability to digest milk as they
mature due to the decreasing transcriptional “silence” of the LCT gene
over time. However, some humans have the ability to digest lactose into
adulthood also known as “lactase persistence”). This means they have a
genetic mutation that leads to continuous transcriptional activity of
LCT. Lactase persistence mutations are common in populations with a long
history of pastoral farming, such as northern European and North African
populations. It is believed that lactase persistence evolved because the
ability to digest milk was nutritionally beneficial. More information
about lactase persistence will be covered in Chapter 14.
MENDELIAN GENETICS AND OTHER PATTERNS OF INHERITANCE
Gregor Johann Mendel 1822–1884) is often described as the “Father of
Genetics.” Mendel was a monk who conducted pea plant breeding
experiments in a monastery located in the present-day Czech Republic
Figure 3.27). After several years of experiments, Mendel presented his
work to a local scientific community in 1865 and published his findings
the following year. Although his meticulous effort was notable, the
importance of his work was not recognized for another 35 years. One
reason for this delay in recognition is that his findings did not agree
with the predominant scientific viewpoints on inheritance at the time.
For example, it was believed that parental physical traits “blended”
together and offspring inherited an intermediate form of that trait. In
contrast, Mendel showed that certain pea plant physical traits e.g.,
flower color) were passed down separately to the next generation in a
statistically predictable manner. Mendel also observed that some
parental traits disappeared in offspring but then reappeared in later
generations. He explained this occurrence by introducing the concept of
“dominant” and “recessive” traits. Mendel established a few fundamental
laws of inheritance, and this section reviews some of these concepts.
Moreover, the study of traits and diseases that are controlled by a
single gene is commonly referred to as Mendelian genetics.
Mendelian Genetics
Figure 3.27
Figure 3.28
The physical appearance of a trait is called an organism’s phenotype.
Figure 3.28 shows pea plant Pisum sativum) phenotypes that were studied
by Mendel, and in each of these cases the physical traits are controlled
by a single gene. In the case of Mendelian genetics, a phenotype is
determined by an organism’s genotype. A genotype consists of two gene
copies, wherein one copy was inherited from each parent. Gene copies are
also known as alleles Figure 3.29), which means they are found in the
same gene location on homologous chromosomes. Alleles have a
nonidentical DNA
sequence, which means their phenotypic effect can be different. In other
words, although alleles code for the same trait, different phenotypes
can be produced depending on which two alleles i.e., genotypes) an
organism possesses. For example, Mendel’s pea plants all have flowers,
but their flower color can be purple or white. Flower color is therefore
dependent upon which two color alleles are present in a genotype.
Figure 3.29
A Punnett square is a diagram that can help visualize Mendelian
inheritance patterns. For instance, when parents of known genotypes
mate, a Punnett square can help predict the ratio of Mendelian genotypes
and phenotypes that their offspring would possess. Figure 3.30 is a
Punnett square that includes two heterozygous parents for flower color
Bb). A heterozygous genotype means there are two different alleles for
the same gene. Therefore, a pea plant that is heterozygous for flower
color has one purple allele and one white allele. When an organism is
homozygous for a specific trait, it means their genotype consists of two
copies of the same allele. Using the Punnett square example Figure
3.30), the two heterozygous pea plant parents can produce offspring with
two different homozygous genotypes BB or bb) or offspring that are
heterozygous Bb).
Figure 3.30
A pea plant with purple flowers could be heterozygous Bb) or homozygous
BB). This is because the purple color allele B) is dominant to the white
color allele b), and therefore it only needs one copy of that allele to
phenotypically express purple flowers. Because the white flower allele
is recessive, a pea plant must be homozygous for the recessive allele in
order to have a white color phenotype bb). As seen by the Punnett square
example Figure 3.30), three of four offspring will have purple flowers
and the other one will have white flowers.
The Law of Segregation was introduced by Mendel to explain why we can
predict the ratio of genotypes and phenotypes in offspring. As discussed
previously, a parent will have two alleles for a certain gene with each
copy on a different homologous chromosome). The Law of Segregation
states that the two copies will be segregated from each other and will
each be distributed to their own gamete. We now know that the process
where that occurs is meiosis.
Offspring are the products of two gametes combining, which means the
offspring inherits one allele from each gamete
for most genes. When multiple offspring are produced like with pea plant
breeding), the predicted phenotype ratios are more clearly observed. The
pea plants Mendel studied provide a simplistic model to understand
single-gene genetics. While many traits anthropologists are interested
in have a more complicated inheritance e.g., are informed by many
genes), there are a few known Mendelian traits in humans. Additionally,
some human diseases also follow a Mendelian pattern of inheritance
Figure 3.31). Because humans do not have as many offspring as other
organisms, we may not recognize Mendelian patterns as easily. However,
understanding these principles and being able to calculate the
probability that an offspring will have a Mendelian phenotype is still
important.
Mendelian disorder Gene Mendelian disorder Gene
Alpha Thalassemia HBA1 Maple Syrup Urine Disease: Type 1A BCKDHA
Androgen Insensitivity Syndrome Bloom Syndrome AR BLM Mitochondrial
MTHFR DNA Depletion Syndrome Deficiency TYMP MTHFR
Canavan Disease Cartilage-Hair Hypoplasia ASPA RMRP Oculocutaneous
Oculocutaneous Albinism: Type 1 Albinism: Type 3 TYR TYRP1
Cystic Fibrosis CFTR Persistent Type I Mullerian Duct Syndrome: AMH
Familial Chloride Diarrhea Fragile X Syndrome SLC26A3 FMR1 Polycystic
Sickle-cell Kidney Disease anemia PKHD1 HBB
Glucose-6-Phosphate Dehydrogenase Deficiency Hemophilia A G6PD F8
Spermatogenic Spinal Muscular failure Atrophy: SMN1 Linked USP9Y SMN1
Huntington disease Hurler Syndrome HTT IDUA Tay-Sachs Wilson Disease
Disease HEXA ATP7B
Figure 3.31 Human diseases that follow a Mendelian pattern of inheritance.
Example of Mendelian Inheritance: The ABO Blood Group System
In 1901, Karl Landsteiner at the University of Vienna published his
discovery of ABO blood groups. This was a result of conducting blood
immunology experiments in which he combined the blood of individuals who
possess different blood cell types and observed an agglutination
clotting) reaction. The presence of agglutination implies there is an
incompatible immunological reaction, whereas no agglutination will occur
in individuals with the same blood type. This work was clearly important
because it resulted in a higher survival rate of patients who received
blood transfusions.
Blood transfusions from someone with a different type of blood causes
agglutinations, and the resulting coagulated blood can not easily pass
through blood vessels, resulting in death. Accordingly, Landsteiner
received the Nobel Prize
1930) for explaining the ABO blood group system.
Blood cell surface antigens are proteins that coat the surface of red
blood cells, and antibodies are specifically “against” or “anti” to the
antigens from other blood types. Thus, antibodies are responsible for
causing agglutination between incompatible blood types. Understanding
the interaction of antigens and antibodies helps to determine ABO
compatibility amongst blood donors and recipients. In order to better
understand blood phenotypes and ABO compatibility, blood cell antigens
and plasma antibodies are presented in Figure 3.32. Individuals that are
blood type A have A antigens on the red blood cell surface, and anti-B
antibodies, which will bind with B antigens should they come in contact.
Alternatively, individuals with blood type B have B antigens and anti-A
antibodies. Individuals with blood type AB have both A and B antigens
but do not produce antibodies for the ABO system. This does not mean
type AB does not have any antibodies, just that anti-A or anti-B
antibodies are not produced. Individuals who are blood type O have
nonspecific antigens but produce both anti-A and anti-B antibodies.
Figure 3.32
Figure 3.33 shows a table of the ABO allele system, which has a
Mendelian pattern of inheritance. Both the A and B alleles function as
dominant alleles, so the A allele always codes for the A antigen, and
the B allele codes for the B antigen. The O allele differs from A and B,
because it codes for a nonfunctional antigen protein, which means there
is no antigen present on the cell surface of O blood cells. To have
blood type O, two copies of the O allele must be inherited, one from
each parent, thus the O allele is considered recessive. Therefore,
someone who is a heterozygous AO genotype is phenotypically blood type A
and a genotype of BO is blood type B. The ABO blood system
Figure 3.33
also provides an example of codominance, which is when the effect of
both alleles is observed in the phenotype. This is true for blood type
AB: when an individual inherits both the A and B alleles, then both A
and B antigens will be present on the cell surface.
Also found on the surface of red blood cells is the rhesus group
antigen, known as “Rh factor.” In reality, there are several antigens on
red blood cells independent from the ABO blood system, however, the Rh
factor is the second most important antigen to consider when determining
blood donor and recipient compatibility. Rh antigens must also be
considered when a pregnant mother and her baby have incompatible Rh
factors. In such cases, a doctor can administer necessary treatment
steps to prevent pregnancy complications and hemolytic disease, which is
when the mother’s antibodies break down the newborn’s red blood cells.
An individual can possess the Rh antigen be Rh positive) or lack the Rh
antigen be Rh negative). The Rh factor is controlled by a single gene
and is inherited independently of the ABO alleles. Therefore, all blood
types can either be positive O+, A+, B+, AB+) or negative O-, A-, B-, AB-).
Individuals with O+ red blood cells can donate blood to A+, B+, AB+, and
O+ blood type recipients. Because O- individuals do not have AB or Rh
antigens, they are compatible with all blood cell types and are referred
to as “universal donors.” Individuals that are AB+ are considered to be
“universal recipients” because they do not possess antibodies against
other blood types.
Mendelian Patterns of Inheritance and Pedigrees
A pedigree can be used to investigate a family’s medical history by
determining if a health issue is inheritable and will possibly require
medical intervention. A pedigree can also help determine if it is a
Mendelian recessive or dominant genetic condition. Figure 3.34 is a
pedigree example of a family with Huntington’s disease, which has a
Mendelian dominant pattern of inheritance. In a standard pedigree, males
are represented by a square and females are represented by a circle.
When an individual is affected with a certain condition, the square or
circle is filled in as a solid color. With a dominant condition, at
least one of the parents will have the disease and an offspring will
have a 50% chance of inheriting the affected chromosome. Therefore,
dominant genetic conditions tend to be present in every generation. In
the case of Huntington’s, some individuals may not be diagnosed until
later in adulthood, so parents may unknowingly pass this dominantly
inherited disease to their children.
Figure 3.34
Because the probability of inheriting a disease-causing recessive allele
is more rare, recessive medical conditions can skip generations. Figure
3.35 is an example of a family that carries a recessive cystic fibrosis
mutation. A parent that is heterozygous for the cystic fibrosis allele
has a 50% chance of passing down their affected chromosome to the next
generation. If a child has a recessive disease, then it means both of
their parents are carriers heterozygous) for that condition. In most
cases, carriers for recessive conditions show no serious medical
symptoms. Individuals whose family have a known medical history for
certain conditions sometimes seek family planning services see the
Genetic Testing section).
Figure 3.35
Pedigrees can also help distinguish if a health issue has an autosomal
or X-linked pattern of inheritance. As previously discussed, there are
23 pairs of chromosomes and 22 of these pairs are known as autosomes.
The provided pedigree examples Figure 3.34–35) are autosomally linked
genetic diseases. This means the genes that cause the disease are
located on one of the chromosomes numbered 1 to 22. Disease causing
genes can also be X-linked, which means they are located on the X
chromosome.
Figure 3.36 depicts a family in which the mother is a carrier for the X-
linked recessive disease Duchenne Muscular Dystrophy DMD). The mother is
a carrier for DMD, so daughters and sons will have a 50% chance of
inheriting the pathogenic DMD allele. Because females have two X
chromosomes, females will not have the disease although in rare cases,
female carriers may show some symptoms of the disease). On the other
hand, males who inherit a copy of an X-linked pathogenic DMD allele will
typically be affected with the condition. Males are more susceptible to
X-linked conditions because they only have one X chromosome. Therefore,
when evaluating a pedigree, if a higher proportion of males are affected
with the disease, this could suggest the disease is X-linked recessive.
Finally, Y-linked traits are very rare because compared to other
chromosomes, the Y chromosome is smaller and only has a few active
transcribed) genes.
Figure 3.36
Complexity Surrounding Mendelian Inheritance
Figure 3.37
Pea plant trait genetics are relatively simple compared to what we know
about genetic inheritance today. The vast majority of genetically
controlled traits are not strictly dominant or recessive, so the
relationship among alleles and predicting phenotype is often more
complicated. For example, a heterozygous genotype that exhibits an
intermediate phenotype of both alleles is known as incomplete dominance.
In snapdragon flowers, the red flower color R) is dominant and white is
recessive r). Therefore, the homozygous dominant RR is red and
homozygous recessive rr is white. However, because the R allele is not
completely dominant, the heterozygote Rr is a blend of red and white,
which results in a pink flower Figure 3.37).
An example of incomplete dominance in humans is the enzyme β-
hexosaminidase A Hex A), which is encoded by the gene HEXA. Patients
with two dysfunctional HEXA alleles are unable to metabolize a specific
lipid-sugar molecule GM2 ganglioside); because of this, the molecule
builds up and causes damage to nerve cells in the brain and spinal cord.
This condition is known as Tay-Sachs disease, and it usually appears in
infants who are three to six months old. Most children with Tay-Sachs do
not live past early childhood. Individuals who are heterozygous for the
functional type HEXA allele and one dysfunctional allele have reduced
Hex A activity. However, the amount of enzyme activity is still
sufficient, so carriers do not exhibit any neurological phenotypes and
appear healthy.
Some genes and alleles can also have higher penetrance than others.
Penetrance can be defined as the proportion of individuals who have a
certain allele and also express an expected phenotype. If a genotype
always produces an expected phenotype, then those alleles are said to be
fully penetrant. However, in the case of incomplete or reduced) penetrance,
an expected phenotype may not occur even if an individual possesses the
alleles that are known to control a trait or cause a disease.
A well-studied example of genetic penetrance is the cancer-related genes
BRCA1 and BRCA2. Mutations in these genes can affect crucial processes
such as DNA repair, which can lead to breast and ovarian cancers.
Although BRCA1 and BRCA2 mutations have an autosomal dominant pattern of
inheritance, it does not mean an individual will develop cancer if they
inherit a pathogenic allele. Several lifestyle and environmental factors
can also influence the risk for developing cancer. Regardless, if a
family has a history of certain types of cancers, then it is often
recommended that genetic testing be performed for individuals who are at
risk. Moreover, publically available genetic testing companies are now
offering health reports that include BRCA1/2 allele testing see the
Genetic Testing section).
POLYGENIC TRAITS
While Mendelian traits tend to be influenced by a single gene, the vast
majority of human phenotypes are polygenic traits. The term polygenic
means “many genes.” Therefore, a polygenic trait is influenced by many
genes that work together to produce the phenotype. Human phenotypes such
as hair color, eye color, height, and weight are examples of polygenic
traits. Complex diseases e.g., cardiovascular diseases, Alzheimer’s, and
Schizophrenia) also have a polygenic basis.
Human hair color is an example of a polygenic trait. Hair color is
largely determined by the type and quantity of a pigment called melanin,
which is produced by a specialized cell type within the skin called
melanocytes. The quantity and ratio of melanin pigments determine black,
brown, blond, and red hair colors. MC1R is a well-studied gene that
encodes a protein expressed on the surface of melanocytes that is
involved in the production of eumelanin pigment. Typically, people with
two functional copies of MC1R have brown hair. People with reduced
functioning MC1R allele copies tend to produce pheomelanin, which
results in blond or red hair. However, MC1R alleles have variable
penetrance, and studies are continually identifying new genes e.g., TYR,
TYRP1, SLC24A5, and KITLG) that also influence hair color. Individuals
with two non-functioning copies of the gene TYR have a condition called
oculocuteaneous albinism—their melanocytes are unable to produce melanin
so these individuals have white hair, light eyes, and pale skin.
In comparison to Mendelian disease, complex diseases tend to be more
prevalent in humans. Complex diseases can also run in families, but they
often do not have a clear pattern of inheritance. Geneticists may not
know all of the genes involved with a given complex disease. In addition
to different gene combinations, complex diseases are also influenced by
environment and lifestyle factors. Moreover, how much each of these
determinants contribute to a disease phenotype can be difficult to
decipher. Therefore, predicting medical risk is often a significant
challenge. For instance, cardiovascular diseases CVDs) continue to be
one of the leading causes of death around the world. Development of CVDs
has been linked to malnutrition during fetal development, high fat and
sedentary lifestyles, smoking/drug usage, adverse socioeconomic
conditions, and various genes. Human environments are diverse, and
public health research including the field of Human Biology can help
identify risk factors and behaviors associated with chronic diseases.
Large-scale genetic studies can also help elucidate some of these
complex relationships.
GENOMICS AND EPIGENETICS
The genome is all of the genetic material for an organism. In the case
of humans, this includes 46 chromosomes and mtDNA. The human genome
contains approximately three billion base pairs of DNA and has regions
that are both
noncoding and coding. Scientists now estimate that the human genome
contains 20,000–25,000 protein-coding genes, with each chromosome
containing a few hundred to a few thousand genes. As our knowledge of
heredity increases, researchers have begun to realize the importance of
epigenetics, or changes in gene expression that do not result in a
change of the underlying DNA sequence. Epigenetics research is also
crucial for unraveling gene regulation, which involves complex
interactions between DNA, RNA, proteins, and the environment.
Genomics
The vast majority of the human genome is noncoding, meaning there are no
instructions to make a protein or RNA product in these regions.
Historically, noncoding DNA was referred to as “junk DNA” because these
vast segments of the genome were thought to be irrelevant and non-
functional. However, continual improvement of DNA sequencing technology
along with world-wide scientific collaborations and consortia have
contributed to our increased understanding of how the genome functions.
Through these technological advances and collaborations, we have since
discovered that many of these noncoding DNA regions are involved in
dynamic genetic regulatory processes.
Genomics is a diverse field of molecular biology that focuses on genomic
evolution, structure and function; gene mapping; and genotyping
determining the alleles present). Evolutionary genomics determined that
humans and chimpanzees share a significant portion of shared DNA
sequence about 98.8%). Given the phenotypic differences between humans
and chimpanzees, having a DNA sequence difference of 1.2% seems
surprising. However, a lot of genomics research is also focused on
understanding how noncoding genomic regions influence how individual
genes are turned “on” and “off” i.e., regulated). Therefore, although
DNA sequences are identical, regulatory differences in noncoding genetic
regions e.g., promoters) are believed to be largely responsible for the
physical differences between humans and chimpanzees.
Further understanding of genomic regulatory elements can lead to new
therapies and personalized treatments for a broad range of diseases. For
example, targeting the regulatory region of a pathogenic gene to “turn
off” its expression can prevent its otherwise harmful effects. Such
molecular targeting approaches can be personalized based on an
individual’s genetic makeup. Genome-wide association studies GWAS) seek
to determine genes that are linked to complex traits and diseases and
typically require significant computational efforts. This is because
millions of DNA sequences must be analyzed and GWAS sometimes include
thousands of participants. During the beginning of the genomics field,
most of the large-scale genomics studies only included North American,
European, and East Asian participants and patients. Researchers are now
focusing on increasing ethnic diversity in genomic studies and
databases. In turn, accuracy of individual disease risk across all human
populations will be improved and more rare disease-causing alleles will
be identified.
Epigenetics
All cells within your body have the same copy of DNA. For example, a
brain neuron has the same DNA blueprint as does a skin cell on your arm.
Although these cells have the same genetic information, they are
considered specialized. The reason all cells within the body have the
same DNA but different morphologies and functions is that different
subsets of genes are turned “on” and “off” within the different cell
types. A more precise explanation is that there is differential
expression of genes among different cell types. In the case of neuronal
cells, a unique subset of genes are active that allow them to grow axons
to send and receive messages. This subset of genes will be inactive in
non-neuronal cell types such as skin cells. Epigenetics is a branch of
genetics that studies how these genes are regulated through mechanisms
that do not change the underlying DNA sequence. Special Topics:
Epigenetics and X Chromosome Inactivation details a well-known example
of epigenetic regulation.
The prefix epi means “on, above, or near,” and epigenetic mechanisms
such as DNA methylation and histone modifications occur on, above, or
near DNA. The addition of a methyl group —CH₃) to DNA is known as DNA
methylation Figure 3.38). DNA methylation and other modifications made
to the histones around which DNA are wrapped are thought to make
chromatin more compact. This DNA is inaccessible to transcription
factors and RNA polymerases, thus preventing genes from being turned on
i.e., transcribed). Other histone modifications have the opposite effect
by loosening chromatin, which makes genes accessible to transcription
factors.
It is important to note that environmental factors can alter DNA
methylation and histone modifications and also that these changes can be
passed from generation to generation. For example, someone’s epigenetic
profile can be altered during a stressful time e.g., natural disasters,
famine, etc.), and those regulatory changes can be inherited by the next
generation. Moreover, our epigenetic expression profile changes as we
age. For example, certain places in our genome become “hyper” or “hypo”
methylated over time. Identical twins also have epigenetic profiles that
become more different as they age. Researchers are only beginning to
understand what all of these genome-wide epigenetic changes mean.
Scientists have also discovered that changes in epigenetic modifications
can alter gene expression in ways that contribute to diseases. It is
also important to note that, unlike DNA mutations which permanently
change the nucleotide sequence), epigenetic changes can be easily
reversed. A lot of research now focuses on how drugs can alter or
modulate changes in DNA methylation and histone modifications to treat
diseases such as cancer.
Figure 3.38
SPECIAL TOPIC: EPIGENETICS AND X CHROMOSOME INACTIVATION
Mary Lyon was a British geneticist that presented a hypothesis for X
chromosome inactivation called the Lyon hypothesis) based on her work
and other studies of the day. Females inherit two X chromosomes, one
from each parent. Males have one functional X chromosome; however, this
does not mean females have more active genes than males. During the
genetic embryonic development of many female mammals, one of the X
chromosomes is inactivated at random, so females have one functional X
chromosome. The process of X chromosome inactivation in females occurs
through epigenetic mechanisms, such as DNA methylation and histone
modifications. Recent studies have analyzed the role of a long noncoding
RNA called X-inactive specific transcript XIST), which is largely
responsible for the random silencing of one of the X chromosomes. The
presence of two X chromosomes is the signal for XIST RNA to be expressed
so that one X chromosome can be inactivated. However, some cells may
have an active paternal X chromosome while other cells may have an
active maternal X chromosome. This phenomenon is easily seen in calico
and tortoiseshell cats Figure 3.39). In cats, the gene that controls
coat color is found on the X chromosome. During early embryo
development, random inactivation of X chromosomes gives rise to
populations of cells that express black or orange, which results in the
unique coat patterning. Therefore, calico cats are typically always female.
Figure 3.39
GENETIC TESTING
In order to assist with public health efforts, newborn screening for
genetic diseases have been available in the United States for over 50
years. One of the first available genetic tests was to confirm a
phenylketonuria PKU) diagnosis in infants, which is easily treatable
with a dietary change. Currently, each state decides what genes are
included on newborn screening panels and some states even have programs
to help with infant medical follow-ups.
There are now hundreds of laboratories that provide testing for a few
thousand different genes that can inform medical decisions for infants
and adults. What has made this industry possible are the advancements in
technology and decreased cost to patients. Moreover, genetic testing has
been made available publicly to anyone without the assistance of medical
professionals.
Polymerase Chain Reaction (PCR) and Sanger Sequencing
One of the most important inventions in the genetics field was
polymerase chain reaction (PCR). In order for researchers to visualize
and therefore analyze DNA, the concentration must meet certain
thresholds. In 1985, Kary Mullis developed PCR, which can amplify
millions of copies of DNA from a very small amount of template DNA
Figure 3.40). For example, a trace amount of DNA at a crime scene can be
amplified and tested for a DNA match. Also, aDNA is typically degraded,
so a few remaining molecules of DNA can be amplified to reconstruct
ancient genomes. The PCR assay uses similar biochemical reactions to our
own cells during DNA replication.
Figure 3.40
In Sanger sequencing, PCR sequences can be analyzed at the nucleotide
level with the help of fluorescent labeling. Several different types of
alleles and genetic changes can be detected in DNA by using this
analysis. Figure 3.41 shows someone who is heterozygous for a single
nucleotide allele. These methods continue to be used extensively
alongside larger-scale genome technologies.
Figure 3.41
Genetic Biotechnology and Clinical Testing
Figure 3.42
Genetic innovations are transforming the healthcare industry. However,
the different types of technology and the results of these tests often
include a learning curve for patients, the public, and medical
practitioners. Microarray technology, when DNA samples are genotyped or
“screened”) for specific alleles, has been available for quite some time
Figure 3.42). Presently, microarray chips can include hundreds of
alleles that are known to be associated with various diseases. The
microarray chip only binds with a DNA sample if it is “positive” for
that particular allele and a fluorescent signal is emitted, which can be
further analyzed.
If a patient is suspected of having a rare genetic condition that cannot
be easily diagnosed or the diagnosis is entirely unknown, whole genome
sequencing may be recommended by a doctor. Next-generation sequencing
(NGS) is a newer technology that can screen the entire genome by
analyzing millions of sequences within a single machine run Figure
3.43). However, sequencing the entire genome yields a significant amount
of data and information. Therefore, clinical NGS genetic testing
typically only
includes a small subset of the genome known to have pathogenic disease-
causing mutations.
Figure 3.43
There is a diversity of clinical genetics tests available to assist
patients with making medically informed decisions about family planning
and health, including assistance with in vitro fertilization IVF)
procedures and embryo genetic screening. To ensure accuracy, it is
highly important that all clinical laboratories are continually
regulated. The Clinical Laboratory Improvement Amendments CLIA) are
United States federal standards that all human laboratory testing
clinics must follow. A major benefit provided by some clinical genetic
testing companies is access to genetic counselors, who have specialized
education and training in medical genetics and counseling. Both partners
are usually tested to see if there is a risk for passing on a disease to
a child. Counselors use their skillset to aid patients and doctors with
risk assessment for genetic diseases and interpretation of genetic
testing results. Genetic counselors also guide and support patients when
making impactful medical decisions.
Direct-to-Consumer (DTC) Genetic Testing
Figure 3.44
Genetic testing that is performed without the guidance of medical
professionals is called direct-to-consumer DTC) genetic testing.
Companies that sell affordable genome sequencing products to the public
continue to increase in number and popularity. These companies have
marketing campaigns typically based on the notion of “personal
empowerment,” which can be achieved by “knowing more about your DNA.”
For example, if you are identified as having a slightly increased risk
for developing celiac disease Figure 3.44), then you may be motivated to
modify your dietary consumption by removing gluten from your diet.
Another scenario is that you could test positive for a known pathogenic
BRCA1 or BRCA2 allele. In this case, you may want to follow up with
additional testing from a medical facility, which could lead to life-
altering decisions. DNA sequencing products for entertainment purposes
are also available. For example, by having your “Vinome” analyzed, you
can discover if you are more predisposed to liking Pinots as your
favorite wine. Additionally, an individual and their partner can be
genotyped to predict what physical characteristics their baby might inherit.
DTC testing typically lacks genetic counselor services and regulations
are not as strict. This has led to some controversies including company
genetic products that provide health information. The company 23andMe
was the first on the market to offer DTC health testing, and in 2013,
the U.S. Food and Drug Administration FDA) intervened. 23andMe worked
toward complying with FDA regulations and then gained approval to offer
testing on a few medically related genes. In 2017, 23andMe offered a
“Late-Onset Alzheimer’s Disease” genetic risk report. Such offerings
have been criticized because customers could receive results they may
not fully be able to interpret. In turn, this could increase the stress
of participants sometimes called the “burden of knowing”) and could also
lead to unnecessary medical intervention. In order to address this
issue, 23andMe now provides disclaimers and also interactive learning
modules that customers must complete if they wish to view certain
genotyping results. However, individuals who tested positive for a
disease-causing allele have also been able to successfully seek medical
help. The potential for harm and the proposed benefits of DTC testing
continue to be a topic of debate and investigation.
Ancestry percentage tests are also widely popular Figure 3.45).
Customers are genotyped and their alleles are assigned to different
groups from around the world Chapter 4 will discuss human biological
variation in further detail). However, the scientific significance and
potential harm of ancestry percentage tests have been called into
question. For example, most alleles tested are not exclusive to one
population, and populations may be defined differently depending on the
testing companies. If an allele is assigned to the “Irish” population,
there is a good chance that the allele may have evolved in a different
cultural group or region that pre-dates the formation of the country
Ireland. In other words, genetic variation often pre-dates the origins
the population and geographical names of the region used by genetic
testing companies. Another critique is that someone’s identity need not
include biological relationships. Individuals also have the option to
find and connect online with individuals with whom they share portions
of their genome, which has resulted in both positive and negative
outcomes. Another interesting consideration is that law enforcement is
currently developing forensic techniques that involve mining DTC genomic
databases for the purpose of identifying suspects linked to crimes.
Regardless of these various considerations, there are now millions of
individuals worldwide who have “unlocked the secrets” of their DNA, and
the multi-billion dollar genomics market only continues to grow.
As you have seen in this chapter, DNA provides instructions to our
cells, which results in the creation and regulation of proteins.
Understanding these fundamental mechanisms is important to being able to
understand how the evolutionary process works see Chapter 4) and how
humans vary from one another see Chapters 13 and 14). It is also the
advancement in genetic technologies—including ancient DNA studies,
genomics, and epigenetics—that has led to new anthropological
understandings about our biological relationships to other living
extant) and extinct primates. Many of these genetic discoveries will be
covered in the chapters to come.
Figure 3.45
Review Questions
* What is the purpose of DNA replication? Explain in a few sentences
what happens during DNA replication. When do DNA mutations happen?
And how does this create phenotypic variation i.e., different
phenotypes of the same physical trait)?
* Using your own words, what are homologous chromosomes and sister
chromatids? What are the key differences between mitosis and meiosis?
* Determine if the pedigree diagram below represents an autosomal
dominant, autosomal recessive, or X-linked recessive pattern of
inheritance. You should write the genotype i.e., AA, Aa, or aa)
above each square to help you note: there may sometimes be two
possible answers for a square’s genotype). Please also explain why
you concluded that particular pattern of inheritance.
Figure 3.46
* Use base pairing rules to transcribe the following DNA template
sequence into mRNA: GTAAAGGTGCTGGCCATC. Next, use the protein codon
table Figure 3.25) to translate the sequence. In regard to
transcription, explain what the significance is of the first and
last codon/protein in the sequence.
* In your opinion, what do you think the benefits are of direct-to-
consumer DTC) genetic testing? What are the drawbacks and/or greater
ethical concerns? Do you think benefits outweigh concerns?
* Imagine that you submit your DNA sample to a genetic testing company
and among the various diseases for which they test, there is an
allele that is associated with late-onset Alzheimer’s disease. You
have the option to view your Alzheimer’s result or to not view your
result. What do you do and why?
Key Terms
Adenosine triphosphate (ATP): A high-energy compound produced by
mitochondria that powers cellular processes.
Allele: A non-identical DNA sequence found in the same gene location on
a homologous chromosome, or gene copy, that codes for the same trait but
produces a different phenotype.
Amino acids: Organic molecules that are the building blocks of protein.
Each of the 20 different amino acids have their own unique chemical
property. Amino acids are also chained together to form proteins.
Ancient (aDNA): DNA that is isolated from organic remains often dating
from hundreds to thousands of years ago. Also, aDNA is typically
degraded i.e., damaged) due to exposure to the elements such as heat,
acidity, and humidity.
Aneuploid: A cell with an unexpected amount of chromosomes. The loss or
gain of chromosomes can occur during mitotic or meiotic division.
Antibodies: Immune-related proteins that can detect and bind to foreign
substances in the blood such as pathogens. Apoptosis: A series of
molecular steps that is activated leading to cell death. Apoptosis can
be activated when a cell fails checkpoints during the cell cycle;
however, cancer cells have the ability to avoid apoptosis.
Autosomal: Refers to a pattern of inheritance where an allele is located
on an autosome. Base pairs: Chemical bonding between nucleotides, like
adenine A) and thymine T) or cytosine C) and guanine G) in DNA; or A)
and uracil U) in RNA
Carbohydrate: Molecules composed of carbon and hydrogen atoms that can
be broken down to supply energy. Carrier: An individual who has a
heterozygous genotype that is typically associated with a disease.
Cell cycle: A cycle the cell undergoes with checkpoints between phases
to ensure that DNA replication and cell division occur properly.
Cell surface antigen: A protein that is found on a red blood cell’s
surface. Centromere: A structural feature that is defined as the
“center” of a chromosome and which creates two different arm lengths.
Term also refers to the region of attachment for microtubules during
mitosis and meiosis.
Chromatin: DNA wrapped around histone complexes. During cell division,
chromatin becomes a condensed chromosome.
Chromosome: DNA molecule that is wrapped around protein complexes,
including histones. Codominance: The effects of both alleles in a
genotype can be seen in the phenotype. Codons: A sequence that comprises
three DNA nucleotides that together code for a protein. Complex
diseases: A category of diseases that are polygenic and are also
influenced by environment and lifestyle factors. Cytoplasm: The “jelly-
like” matrix inside of the cell that contains many organelles and other
cellular molecules. Deleterious: A mutation that increases an organism’s
susceptibility to disease.
Deoxyribonucleic acid (DNA): A molecule that carries the hereditary
information passed down from parents to offspring.
DNA can be described as a “double helix”’ shape. It includes two chains
of nucleotides held together by hydrogen bonds with a sugar-phosphate
backbone.
Diploid: Refers to an organism or cell with two sets of chromosomes. DNA
methylation: Methyl groups bind DNA, which modifies the transcriptional
activity of a gene by turning it “on” or “off.”
DNA polymerase: Enzyme that adds nucleotides to existing nucleic acid
strands during DNA replication. These enzymes can be distinguished by
their processivity e.g., DNA replication).
DNA replication: Cellular process in which DNA is copied and doubled.
DNA sequence: The order of nucleotide bases. A DNA sequence can be
short, long, or representative of entire chromosomes or organismal genomes.
Dominant: Refers to an allele for which one copy is sufficient to be
visible in the phenotype. Elongation: The assembly of new DNA from
template strands with the help of DNA polymerases. Enzymes: Proteins
responsible for catalyzing accelerating) various biochemical reactions
in cells. Epigenetic profile: The methylation pattern throughout a
genome—that is, which genes and other genomic sites) are methylated and
unmethylated.
Epigenetics: Changes in gene expression that do not result in a change
of the underlying DNA sequence. These changes typically involve DNA
methylation and histone modifications. These changes are reversible and
can also be inherited by the next generation.
Euchromatin: Loosely coiled chromosomes found within the nucleus that is
accessible for regulatory processing of DNA. Eukaryote: Single-celled or
multicelled organism characterized by a distinct nucleus, with each
organelle surrounded by its own membrane.
Exon: Protein-coding segment of a gene. Gametes: Haploid cells referred
to as an egg and sperm that will fuse together during sexual
reproduction to form a diploid organism.
Gene: Segment of DNA that contains protein-coding information and
various regulatory e.g., promoter) and noncoding
e.g., introns) regions.
Genetic recombination: A cellular process that occurs during meiosis I
in which homologous chromosomes pair up and sister chromatids on
different chromosomes physically swap genetic information.
Genome: All the genetic information of an organism.
Genotype: The combination of two alleles that code for or are associated
with the same gene.
Genotyping: A molecular procedure that is performed to test for the
presence of certain alleles or to discover new ones. Haploid: Cell or
organism with one set of chromosomes n = 23).
Helicase: A protein that breaks the hydrogen bonds that hold double-
stranded DNA together.
Heterozygous: Genotype that consists of two different alleles.
Histones: Protein that DNA wraps around to assist with DNA organization
within the nucleus.
Homologous chromosomes: A matching pair of chromosomes wherein one
chromosome is maternally inherited and the other is paternally inherited.
Homozygous: Genotype that consists of two identical alleles.
Incomplete dominance: Heterozygous genotype that produces a phenotype
that is a blend of both alleles. Initiation: The recruitment of proteins
to separate DNA strands and begin DNA replication. Interphase:
Preparatory period of the cell cycle when increased metabolic demand
allows for DNA replication and doubling of the cell prior to cell division.
Introns: Segment of DNA that does not code for proteins. Karyotyping:
The microscopic procedure where the number of chromosomes in a cell is
determined. Lagging strand: DNA template strand that is opposite to the
leading strand. Therefore, DNA replication proceeds discontinuously,
generating Okazaki fragments.
Leading strand: DNA template strand in which replication proceeds
continuously. Lipids: Fatty acid molecules that serves various purposes
in the cell, including energy storage, cell signaling, and structure.
Meiosis: The process that gametes undergo to divide. The end of meiosis
results in four haploid daughter cells. Mendelian genetics: A
classification given to phenotypic traits that are controlled by a
single gene. Messenger RNA (mRNA): RNA molecule that is transcribed from
DNA. Its tri-nucleotide codons are “read” by a ribosome to build a protein.
Microarray technology: A genotyping procedure that utilizes a microarray
chip, which is a collection of thousands of short nucleotide sequences
attached to a solid surface that can probe genomic DNA.
Microbiome: The collective genomes of the community of microorganisms
that humans have living inside of their body. Mitochondrial DNA (mtDNA):
Circular DNA segment found in mitochondria that is inherited maternally.
Mitochondrion: Specialized cellular organelle that is the site for
energy production. It also has its own genome mtDNA). Mitosis: The
process that somatic cells undergo to divide. The end of mitosis results
in two diploid daughter cells. Mutation: A nucleotide sequence variation
from the template DNA strand that can occur during replication.
Mutations can also happen during recombination.
Next-generation sequencing: A genotyping technology that involves
producing millions of nucleotide sequences from a single DNA sample)
that are then read with a sequencing machine. It can be used for
analyzing entire genomes or specific regions and requires extensive
program-based applications.
Nuclear envelope: A double-layered membrane that encircles the nucleus.
Nucleic acid: A complex structure like DNA or RNA) that carries genetic
information about a living organism.
Nucleotide: The basic structural component of nucleic acids, which
includes DNA A, T, C, and G) and RNA A, U, C, and G).
Nucleus: Double-membrane cellular organelle that helps protect DNA and
regulation of nuclear activities.
Okazaki fragment: Short DNA strands derived from DNA replication on the
lagging strand. They were discovered by Reiji and Tsuneko Okazaki in the
1960s.
Organelle: A structure within a cell that performs specialized tasks
that are essential for the cell. There are different types of organelles
with their own function.
Pathogenic: A genetic mutation i.e., allele) that has a harmful
phenotypic disease-causing effect.
Penetrance: The proportion of how often the possession of an allele
results in an expected phenotype. Some alleles are more penetrant than
others.
Phenotype: The physical appearance of a given trait.
Phospholipid bilayer: Two layers of lipids that form a barrier due to
the properties of a hydrophilic water-loving) head and a hydrophobic
water-repelling) tail.
Polygenic trait: A phenotype that is controlled by two or more genes.
Polymerase chain reaction (PCR): A molecular biology procedure that can
make copies of genomic DNA segments. A small amount of DNA is used as a
starting template and is then used to make millions of copies.
Primer: A primer is a small sequence of nucleotides that bind DNA to
start the process of DNA replication or PCR. Prokaryote: A single-celled
organism characterized by lack of a nucleus and membrane-enclosed
organelles. Promoter: The region of a gene that initiates transcription.
Transcription factors can bind and DNA methylation may occur at a
promoter site, which can modify the transcriptional activities of a gene.
Protein: Chain of amino acids that fold into a three dimensional
structure that allow a cell to function in a variety of ways.
Protein synthesis: A multi-step process by which amino acids are strung
together by RNA machinery read from a DNA template.
Recessive: Refers to an allele whose effect is not normally seen unless
two copies are present in an individual’s genotype. Ribonucleic acid
(RNA): Single-stranded nucleic acid molecule.There are different RNAs
found within cells and they perform a variety of functions, such as cell
signaling and involvement in protein synthesis.
Ribosomal RNA (rRNA): A ribosome-bound molecule that is used to
correctly assemble amino acids into proteins. Ribosome: An organelle in
the cell found in the cytoplasm or endoplasmic reticulum. It is
responsible for reading mRNA and protein assemblage.
RNA polymerase: An enzyme that catalyzes the process of making RNA from
a DNA template. Sanger-sequencing: A process that involves the usage of
fluorescently labeled nucleotides to visualize DNA PCR fragments) at the
nucleotide level.
Semi-conservative replication: DNA replication in which new DNA is
replicated from an existing DNA template strand.
Sequencing: A molecular laboratory procedure that produces the order of
nucleotide bases i.e., sequences). Sister chromatids: During DNA
replication, sister chromatids are produced on the chromosome. In cell
division, sister chromatids are pulled apart so that two cells can be
formed. In meiosis, sister chromatids are also the sites of genetic
recombination.
Somatic cells: Diploid cells that comprise body tissues and undergo
mitosis for maintenance and repair of tissues. Splicing: The process by
which mature mRNAs are produced. Introns are removed spliced) and exons
are joined together.
Sugar phosphate backbone: A biochemical structural component of DNA. The
“backbone” consists of deoxyribose sugars and phosphate molecules.
Telomere: A compound structure located at the ends of chromosomes to
help protect the chromosomes from degradation after every round of cell
division.
Termination: The halt of DNA replication activity that occurs when a DNA
sequence “stop” codon is encountered. Tissue: A cluster of cells that
are morphologically similar and perform the same task.
Transcription: The process by which DNA nucleotides within a gene) are
copied, which results in a messenger RNA molecule.
Transcription factors: Proteins that bind to regulatory regions of genes
e.g., promoter) and increase or decrease the amount of transcriptional
activity of a gene, including turning them “on” or “off.”
Transfer RNA (tRNA): RNA molecule involved in translation. Transfer RNA
transports amino acids from the cell’s cytoplasm to a ribosome.
Translation: The process by which messenger RNA codons are read and
amino acids are “chained together” to form proteins.
X-linked: Refers to a pattern of inheritance where the allele is located
on the X or Y chromosome.
About the Authors
Hayley Mann, M.A.
Binghamton University, hmann3@binghamton.edu
Hayley Mann
Hayley Mann received her bachelor’s degree in Genetics from the
University of California, Davis, and continued her graduate studies in
Biological and Molecular Anthropology at the California State
University, Sacramento. She is currently a Ph.D. candidate at Binghamton
University, where her dissertation focus is on studying genetic
variation of Pacific Islanders Republic of Vanuatu) and also changes in
health as the result of colonization. Hayley also works in clinical
genomics and specializes in various DNA-sequencing methodologies.
Xazmin Lowman, Ph.D.
University of California, Irvine, xlowman@uci.edu
Xazmin Lowman
Xazmin Lowman received her bachelor’s degree in Physiology from the
University of Arizona. She pursued her doctorate in cancer biology at
the University of Minnesota, where she studied how blood cancers evade
cell death. Currently, her scientific interests have led to a
postdoctoral fellowship at the University of California, Irvine, where
she studies how solid tumors adapt to metabolic stress. Beyond figuring
out the mechanisms that drive cancer, she enjoys traveling to learn of
other cultures and share her own upbringing on the Navajo reservation.
Malaina Gaddis, Ph.D.
malainagaddis@gmail.com
Malaina Gaddis
Malaina Gaddis studied biology at Brigham Young University in Utah and
then earned a Ph.D. in genetics and molecular and cellular biology at
the University of Southern California. During her Ph.D. studies, she
investigated small molecule inhibitors that alter epigenetic
modifications and gene expression in cancer cells. Following her Ph.D.,
she focused on the business side of the biotech industry by completing a
master’s degree in bioscience management at the Keck Graduate Institute.
Malaina is especially interested in using genomics to further genetic
testing and personalized treatment and currently works as a genome
variation scientist.
For Further Exploration
Websites
National Human Genome Research Institute https://www.genome.gov/
Genetics Home Reference https://
ghr.nlm.nih.gov/
Genetics Generation http://knowgenetics.org/
yourgenome https://www.yourgenome.org/
Cardiovascular Disease: Genes are Important, but Health-Related
Behaviors and Lifestyle Choices Can Make or Break
Your Health http://ehrweb.aaas.org/ehr/books/3_howard.html
Gene Sequencing Speeds Diagnosis of Deadly Newborn Diseases http://
www.pbs.org/wgbh/nova/next/body/
newborn-gene-sequencing/
Carl Zimmer’s Game of Genomes https://www.statnews.com/feature/game-of-
genomes/season-one/ Illumina Sequencing by Synthesis https://www.youtube.com/
watch?v=fCd6B5HRaZ8
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Figure Attributions
Figure 3.1 Phospholipid Bilayer Anatomy & Physiology, Chapter 3.1,
Figure 2) by OpenStax is used under a CC BY 4.0 License.
Figure 3.2 Nucleic Acid by NIH National Human Genome Research Institute
is in the public domain. Figure 3.3 Amino acids Biology 2e, Figure 3.22)
by OpenStax is used under a CC BY 4.0 License. Figure 3.4 Amino Acids by
NIH National Human Genome Research Institute is in the public domain.
Figure 3.5 Bacteria by NIH National Human Genome Research Institute is
in the public domain. Figure 3.6 Bryum capillare lamina by Kristian
Peters [Fabelfroh 13:07, 2007 UTC)] is used under a CC BY-SA 3.0
License. Figure 3.7 Cell Membrane Anatomy & Physiology, Figure 3.4) by
OpenStax is used under a CC BY 4.0 License. Figure 3.8 Organelle by NIH
National Human Genome Research Institute is in the public domain.
Figure 3.9 Nucleus Biology 2e, Figure 4.11) by OpenStax is used under a
CC BY 4.0 License. Figure 3.10 Mitochondrion through an electron
microscope Biology 2e, Figure 4.14) by OpenStax is used under a CC BY
4.0 License.
Figure 3.11 Cell Structure table original to Explorations: An Open
Invitation to Biological Anthropology by Hayley Mann, Xazmin Lowman, and
Malaina Gaddis is under a CC BY-NC 4.0 License.
Figure 3.12a A group of Tsimshian people having a tea party in a tent,
Lax Kw’alaams formerly Port Simpson), B.C., c. 1890 by unknown
photographer at Online MIKAN no. 3368729 Library and Archives Canada
C-060817). Copyright is expired. Figure 3.12b Tsimshian Territory map
original to Explorations: An Open Invitation to Biological Anthropology
by Elyssa Ebding at GeoPlace, California State University, Chico is
under a CC BY-NC 4.0 License.
Figure 3.13 Rosalind Franklin from the personal collection of Jenifer
Glynn by MRC Laboratory of Molecular Biology is used under a CC BY-SA
4.0 License.
Figure 3.14 Histone by NIH National Human Genome Research Institute is
in the public domain. Figure 3.15 Genome by NIH National Human Genome
Research Institute is in the public domain. Figure 3.16 Chromosome
original to Explorations: An Open Invitation to Biological Anthropology
by Katie Nelson is under a CC BY-NC 4.0 License.
Figure 3.17 DNA replication zh by LadyofHats has been designated to the
public domain CC0). Figure 3.18 Cell cycle Biology 2e, Figure 10.5) by
OpenStax is used under a CC BY 4.0 License. Figure 3.19 HeLa-III by
National Institutes of Health NIH) is in the public domain. Figure 3.20
Mitosis original to Explorations: An Open Invitation to Biological
Anthropology by Mary Nelson is under a CC BY-NC 4.0 License. Figure 3.21
Meiosis original to Explorations: An Open Invitation to Biological
Anthropology by Mary Nelson is under a CC BY-NC 4.0 License. Figure 3.22
Transcription by NIH National Human Genome Research Institute is in the
public domain. Figure 3.23 Protein synthesis original to Explorations:
An Open Invitation to Biological Anthropology by Mary Nelson is under a
CC BY-NC 4.0 License. Figure 3.24 Ribosome Biology 2e, Figure 3.34) by
OpenStax is used under a CC BY 4.0 License Figure 3.25 Codon Table by
NIH National Human Genome Research Institute, accessed August 13, 2018
is in the public domain. Figure 3.26 Protein by NIH National Human
Genome Research Institute is in the public domain. Figure 3.27 Mendel´s
statue by Coeli has been designated to the public domain CC0). Figure
3.28 Mendels peas by Mariana Ruiz LadyofHats has been designated to the
public domain CC0 1.0). Figure 3.29 Homozygous by NIH National Human
Genome Research Institute is in the public domain. Figure 3.30 Punnett
square mendel flowers by Madeleine Price Ball Madprime) is used under a
CC BY-SA 3.0 License. Figure 3.31 Mendelian disorders table original to
Explorations: An Open Invitation to Biological Anthropology by Hayley
Mann, Xazmin Lowman, and Malaina Gaddis is under a CC BY-NC 4.0 License.
Figure 3.32 Blood types by Shahinsahar is used under a CC BY-SA 3.0
License. Figure 3.33 ABO Blood Genotypes original to Explorations: An
Open Invitation to Biological Anthropology by Katie Nelson is under a CC
BY-NC 4.0 License. Figure 3.34 Mendelian dominant pattern of inheritance
original to Explorations: An Open Invitation to Biological Anthropology
by Beth Shook is under a CC BY-NC 4.0 License. Figure 3.35 Cystic
fibrosis, Mendelian recessive pattern of inheritance, original to
Explorations: An Open Invitation to Biological Anthropology by Beth
Shook is under a CC BY-NC 4.0 License. Figure 3.36 X-linked recessive
pattern of inheritance original to Explorations: An Open Invitation to
Biological Anthropology by Beth Shook is under a CC BY-NC 4.0 License.
Figure 3.37 Antirrhinum a.k.a. Snap dragon at lalbagh 7112 by Rameshng
is used under a CC BY-SA 3.0 License. Figure 3.38 Epigenetic Control
Biology 2e, Figure 16.7) by OpenStax is used under a CC BY 4.0 License.
Figure 3.39 “Rue” the calico cat by Hayley Mann is under a CC BY-NC 4.0
License. Figure 3.40 PCR electrophoresis gel by Hayley Mann is under a
CC BY-NC 4.0 License.
Figure 3.41 Sanger sequencing with heterozygous result by Hayley Mann is
under a CC BY-NC 4.0 License. Figure 3.42 DNA microarray by Guillaume
Paumier user:guillom) is used under a CC BY-SA 3.0 License. Figure 3.43
Illumina Hiseq 2,000 sequencers, BGI Hong Kong sequencing room by
Scotted400 is used under a CC BY 3.0 License. Figure 3.44 Positive
carrier result for celiac disease allele by Hayley Mann is under a CC
BY-NC 4.0 License. Figure 3.45 DNA ancestry percentage test results by
Hayley Mann is under a CC BY-NC 4.0 License. Figure 3.46 Pedigree
original to Explorations: An Open Invitation to Biological Anthropology
by Beth Shook is under a CC BY-NC 4.0 License.