Y chromosomes and mitochondrial DNA – A new frontier of genetic ancestry

In his famous 1859 book On the Origin of Species, Charles Darwin described the Tree of
Life, noting that evolutionary descent has “sometimes been represented by a great tree.”
To this end, researchers study different types of genetic material such as autosomal DNA
(22 pairs of non-sex chromosomes), sex chromosomes (Y chromosome and X
chromosome) and mitochondrial DNA.
What can our genetic code tell us about where we come from? How are we connected to
one another?

The Origin of Modern Humans

The origin of Homo sapiens, otherwise known as modern humans, has been an ongoing
topic of debate in the field of evolutionary biology since the 19th century. Broadly
speaking, two competing hypotheses have been proposed.
The “out of Africa” hypothesis suggests that modern humans evolved from their most
likely recent common ancestor, Homo erectus, in Africa approximately 200,000 years
ago. Subsequently, modern humans migrated out of Africa to populate the rest of the
world and replaced all other human species, such as Neanderthals and Homo erectus.
In contrast, the “multiregional” hypothesis suggests that human populations migrated
out of Africa to other regions of the world and, over time, each population evolved into
modern humans in parallel, with some mixing, or interbreeding, taking place between
local populations.
Currently, there is more genetic evidence supporting the “out of Africa” hypothesis.
Specifically, the sequencing of female mitochondrial DNA (mtDNA) and the male Y-
chromosomes (Y-DNA) has highlighted that the greatest patterns of genetic diversity are
within Africa. We all share a common African root.
Just as height, facial features, and mannerisms are often shared by related individuals, so
is genetic variation. You can think of evolution like a timer, ticking through genetic
variants. These genetic variants can be identified by sequencing. These genetic variants
can help individuals reconstruct connections between species or human family lineages.
Moreover, as more genetic variation is introduced into the population, the greater
the genetic diversity within a population. MacArthur Fellow Allan Wilson demonstrated
experimental evidence for this concept, known as the “molecular clock,” which allows
scientists to estimate the age of species by using the number of genetic variants as a
proxy.
Mitochondrial DNA (mtDNA)
In the 1980s, Wilson and others showed that modern humans can trace their lineages to a
single human female who existed in Africa around 200,000 years ago. She was given the
title “Mitochondrial Eve.” The mitochondrial function is to produce energy. Mitochondria
are therefore referred to as the powerhouses of our cells. Mitochondria also have their
own small genomes which are distinct from the genetic material on the 46 human
chromosomes found within the nucleus of a cell (nuclear DNA). Mitochondrial DNA
(mtDNA) is passed down exclusively from mother to child because mtDNA in sperm
cells is lost during fertilization. This means that everyone inherits mtDNA from their
mothers. This also includes mitochondrial diseases which are always maternally
inherited. The group of mtDNA mutations or genetic variants, known as a haplotype, tend
to be inherited together. Therefore, one can use mtDNA to deeply trace back his or her
maternal line. Furthermore, full sequencing of mtDNA can also help find relatives and
construct a family tree.

Mitochondrial DNA
Mitochondria are located out of the nucleus in cytoplasm of the cells. They play a central
role in cell life and death. They have small genome, independent of the nuclear DNA-
mitochondrial DNA (mtDNA). Mitochondrial DNAs are circular, double-stranded
molecules, with high copy number, and a higher evolutionary importance compared to
nuclear DNA. They have specific uniparental inheritance only from mothers to their
child, which is useful for tracing matrilineal kinship in many generations [1–4].
Mitochondrial DNA is a proper tool for determination of the origin of different
populations. It is an important object of study in different fields such as evolutionary
anthropology, population genetics, medical genetics, genetic genealogy and forensic
science [1,5,6].
Mitochondrial DNAs are not involved in recombinant processes and their variants are due
only to mutations. Mitochondrial DNA is characterized by a high mutation rate that
allowed the sequential accumulation of neutral mutation-specific base replacements,
especially transitions, which arose approximately at the same time, when people inhabited
different regions all over the world. These mutations form groups of stable haplotypes
and are known as haplogroups. Mitochondrial DNA haplogroups tend to be
geographically restricted and they are used to genetically distinguish populations
The mtDNA variation data can be used for creating genealogical trees that contain
information about the order of the evolutionary processes in space and time.
The mtDNA variation data can be used for creating genealogical trees that contain
information about the order of the evolutionary processes in space and time. The first
mtDNA tree was created by Vigilant et al. [9], and the first five branching points of the
mtDNA tree were from people living in sub-Saharan Africa. The understanding of the
evolution of the mtDNA pedigree helped population geneticists to trace the ancestors of
modern humans to their roots in Africa and their subsequent distribution in the world. It
was determined that the Mitochondrial Eve lived in sub-Saharan Africa 200,000 years
ago.
 Figure 1. Mitochondria have their own genetic material.

Y Chromosomes (Y-DNA)

1. In the nucleus of each cell, the DNA molecule is packaged into thread-like structures
called chromosomes.

2. Most human cells contain 23 pairs of chromosomes. One set of chromosomes comes
from the mother, while the other comes from the father. The twenty third pair is
called the sex chromosomes, while the rest of the 22 pairs are called autosomes.

3. Typically, biologically male individuals have one X and one Y chromosome (XY)
while those who are biologically female have two X chromosomes. However, there
are exceptions to this rule.

4. The sex chromosomes determine the sex of offspring. The father can contribute an X
or a Y chromosome, while the mother always contributes an X.

5. The Y chromosome is one-third the size of the X chromosome and contains about 55
genes while the X chromosome has about 900 genes.

6. In genealogy, the male lineage is often traced using the Y chromosome because it is
only passed down from the father.

7. All individuals carrying a Y chromosome are related through a single XY

ancestor who (likely) lived around 300,000 years ago.

8. The Y chromosome contains a "male-determining gene," the SRY gene, that causes
testes to form in the embryo and results in development of external and internal male
genitalia. If there is a mutation in the SRY gene, the embryo will develop female
genitalia despite having XY chromosomes.

9. Variation in the number of sex chromosomes in a cell is quite common. Some men
have more than two sex chromosomes in all of their cells (the XXY variation is
called the Klinefelter syndrome), and many men lose the Y chromosome from their
cells as they age. Smoking may exacerbate this loss.
10. Some genes that were thought to be lost from the Y chromosome have actually
relocated to other chromosomes.

11. Much of the Y chromosome is composed of repeating DNA segments. Specialized

techniques are needed sequence and determine the arrangement of these highly
similar segments.

12. Many health conditions are thought to be related to changes in genes expressed on the
Y chromosome. This is currently an active area of research.

Additional Resources

Later studies that genotyped Y chromosomes (sometimes abbreviated as yDNA, Y-CHR

or Y-DNA) led to the identification of Mitochondrial Eve’s counterpart, Y-chromosomal
Adam, also from Africa. Only males carry Y chromosomes — females have two X
chromosomes and males have one X and one Y. And, unlike the 22 pairs of autosomes, or
non-sex chromosomes, Y chromosomes do not recombine, or swap DNA, with another
chromosome. Therefore, all the genetic information contained on the Y chromosome is
passed from father to son. This has led to a unique evolution of the Y chromosome that
differentiates it from the X chromosome and the autosomes. The Y chromosome is the
smallest chromosome containing a bit over 57 million base pairs. However, there are
important genes on the Y chromosome including the SRY gene which is responsible for
sex determination between males and females.

The Difference Between Ancestry and Race

Genetic ancestry testing is a way for individuals to learn their genealogy, or family
history, using genetic information. This is possible because your genome carries a
“signature” of your ancestry. As described above, the examination of genetic variants that
are passed down over generations provides scientific clues about who you are related to
and where your ancestors might have come from.
Genetic ancestry is different from what we call race. Race is a cultural and social
construct rather than something that is biologically determined. It is important to
remember that human beings are 99.9% genetically identical, and we are all descendants
of early humans who lived in Africa. That is also where the roots of our Y chromosomes
and mitochondrial DNA converge. Unfortunately, misrepresentations of many scientific
discoveries surrounding ancestry have often reinforced racism. While we believe that
learning about how your genome encodes information your ancestry is incredibly
important.
 Figure 2. Autosomal DNA, Y
chromosomes, and mitochondrial DNA are inherited differently.
At Nebula Genomics, our goal is to empower our customers to have the option to go
beyond genetic tests that are offered by companies like 23andMe and AncestryDNA and
unlock more information about themselves.

Most genetic ancestry tests examine the 22 pairs of non-sex chromosomes, otherwise
known as autosomes or autosomal DNA. Individuals inherit 50% of their autosomal
DNA from each of their parents. Although autosomal DNA provides information about
close relatives and ancestry percentage estimates, it is often difficult to trace one’s
ancestral lineage much further back in time. This is because before a parent passes down
DNA to their children, the pairs of homologous chromosomes go through a series of
random exchanges of DNA fragments. This process is known as recombination. This
means that the farther back in time you go, the less DNA you share with your ancestors.
In contrast, sequencing mtDNA and Y-DNA can allow one to learn about deep ancestral
lineages because mtDNA and Y-DNA do not undergo recombination before they are
passed down from parent to child.
Today, next-generation DNA sequencing can be used to determine every base of mtDNA
and Y-DNA. This generates a much more complete picture of their evolutionary history.
Furthermore, because mtDNA tends to mutate rapidly, genotyping-based DNA tests that
work well for autosomal DNA, fail to capture the genetic variation of mitochondrial
genomes. Full sequencing of Y-DNA and mtDNA has become the new frontier of genetic
ancestry.
Evolutionary genetics

Evolutionary genetics is the study of how genetic variation leads to evolutionary change.
It includes topics such as the evolution of genome structure, the genetic basis of speciation
and adaptation, and genetic change in response to selection within populations.

Evolutionary genetics is concerned with the mechanisms that explain the

existence and maintenance of genetic variation in traits.
Evolutionary genetics aims to understand the diversity of life from a genetic perspective,
using DNA sequences to study population history and evolution. Increasingly, this
involves studies of complete genomes, offering exciting new opportunities to apply a
wealth of data in order to address long-standing questions in evolutionary biology. This
field has important implications for human welfare, and our department has expertise in
the study of human pathogens, notably influenza, as well as addressing fundamental
research questions.

What are the 4 evolutionary processes?

Those factors are natural selection, mutation, genetic drift, and migration (gene
flow).
Mutation All existing genetic variants once arose by mutation. The most common mutational event
in humans is the change of a single base pair (the letters of the DNA), but there are also deletions,
duplications and insertions of base pairs or even longer parts of DNA (copy number variants).
Aneuploidies (chromosomal aberrations), such as the duplication of chromosome 21 which causes
Down syndrome, are rare but massive, accounting for most altered base pairs per birth.

Selection occurs when there is heritable variation in fitness. Natural selection is frequently broken
down into different subcategories. One grouping distinguishes positive, directional selection
(favoring increases), disruptive selection, (favoring extremes), and stabilizing selection, (favoring
decreased variation in a trait). Another grouping considers survival and sexual selection separately.
Sometimes this is differentiated further into “episodes of selection”.

Genetic drift Luck plays a lead role when numbers are small. If there are few carriers of even a highly
beneficial genetic variant, random events can eliminate all of them. Similarly, a deleterious variant
can be fixated by chance, or a beneficial rare variant can randomly get lost in recombination. Either
way, a gene variant may drift to fixation or extinction just by chance. If all variants at a locus are
common (because no single variant is infrequent and the population is large), the law of large
numbers implies that it will take long before either drifts to fixation. In humans, a comparatively
extremely low genetic diversity points to genetic bottlenecks having been an important instance of
drift (Gazave, Chang, Clark, & Keinan, 2013). Bottlenecks may occur through migration, such as when
founder populations emigrated to North America, or when population sizes decreased dramatically
through harsh conditions such as droughts, epidemics or ice ages. If the resulting population is small
and not diverse (e.g. a clan), even beneficial alleles from the parent population may be lost through
drift.

Gene flow (or migration) When individuals carrying certain alleles move from one group to another,
the frequency of alleles in each group also changes. This process is distinguished from unsystematic
genetic drift, because relevant genetic variants may differentially influence the propensity to migrate
and the success in each group and environment.
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