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.” Generations of scientists have been connecting branches between species with a combination of morphological and genetic data. The focus has narrowed over time to the study of connections within species, such as modern humans, rather than between species. 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. As Pulitzer Prize winner Siddhartha Mukherjee writes in his book The Gene: An Intimate History, “Given our rather brief tenure on earth as a species, we are much more alike than unlike each other.” 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 in a process called oxidative phosphorylation. 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 (mtDNA) is separate from 23 pairs of chromosomes.
Figure 1. Mitochondria have their own genetic material.

Y Chromosomes (Y-DNA)

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

In her book The Social Life of DNA, sociologist Alondra Nelson recalls watching the Roots miniseries as a child in the 1970s. Around this time, many African Americans were interested in learning about their African origins. This series told the story of author and journalist Alex Haley, who reconstructed his family’s genealogy, which traced back to the Gambia. In the past, genealogists used oral history archives to reconstruct family histories. However, it was only after the sequencing of the human genome in 2003 that even more individuals became captivated by DNA-based genetic testing kits, a new way to find one’s roots. Early direct-to-consumer genetic ancestry tests were created by FamilyTreeDNA in 2000 and African Ancestry in 2004. 

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, we understand that many individuals are worried about genetic discrimination, for example, on the basis of race. This is why at Nebula Genomics, we are building the first privacy-focused personal genomics service, allowing you to have full control over your data.

Deep Ancestry Analysis with Nebula Genomics

Inheritance of autosomal DNA, mtDNA, and Y-DNA.
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.

At Nebula Genomics, we offer a 30x Whole-Genome Sequencing service that combines everything — autosomal DNA, mtDNA, and Y-DNA sequencing. We are also partnering with FamilyTreeDNA to give you access to the world’s largest mtDNA and Y-DNA databases, allowing you to learn your full family story.

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