by Frank Ryan
“Which is why we all, males and females, get our mitochondrial genetics only from our mothers?”
“Yes. And that explains why our mitochondrial inheritance doesn't follow the Mendelian laws of nuclear inheritance, such as recessive and dominant behavior of genes. The mitochondria also reproduce much more frequently than the nuclear genome, and because they are bacterial genes, and thus less able to correct mistakes, they are even more liable to mutation.”
“So—that's how you get mitochondrial Snips? Haplotypes—and haplogroups?”
“You've got it! And these will be exclusively inherited through our mothers so they will run true to the maternal line, right back to the origin of the haplotype or haplogroup.”
“So there was a woman, back in Elizabethan times, who would have had the same mitochondrial DNA as my mother?”
“The same as you—other than whatever Snips have accumulated in the meantime. And you can go much further back than that. Why not to Roman times, or the beginnings of agriculture in the Fertile Crescent? In fact, you could go much further back still, to the ovaries of the maternal line to the very origins of Homo sapiens.”
As we tootle our whistle and steam along this new railway of mitochondrial DNA, I would like to explain a little more about the way our human history is written into our genome—or, if you like, our two symbiotically linked genomes. One of the key things to grasp is that we have, in essence, three different parts of our holobiontic genome that are libraries of three different genetic histories. One is the mitochondrial genome, which tells us the story of the maternal genetic line—the matrilineage. The Y chromosome, which is part of the nuclear genome, tells us the story of the paternal genetic line—the patrilineage. And the remaining nuclear lineage, which is by far the bulk of our genetic inheritance, tells us far more about our genetic history as a species.
All the while we've been rattling along this mitochondrial railway, we have been glimpsing subtle differences in how this bacterial genome works. For example, the mitochondrial genome is much smaller than that of a single chromosome within the nucleus. The total mitochondrial genome consists of 16,600 nucleotide pairs—sleepers—where the nuclear genome, even in the halved genome of the germ cells, consists of 3.2 billion. There is no shake-up of the mitochondrial chromosomes, as we find during sexual reproduction involving the nuclear genome. In fact, the mitochondrial DNA isn't composed of linear chromosomes at all. The mitochondrial railway consists of a single circular track, as we would find in a bacterial genome, so that, if we take a lengthy journey along the mitochondrial railway track, it will eventually bring us right back to where we began.
“This symbiosis—the event, as you call it, that gave rise to mitochondria—you said it only ever happened once?”
“We know this for certain because all the mitochondria, from every animal, plant, fungus, and the oxygen-breathing less complex organisms, are clearly derived from a single ancestor.”
“You can determine this from the mitochondrial genes?”
“Yes.”
“Why then, if this happened so very long ago, have the two genomes, the mitochondrial and nuclear, not joined up? Wouldn't that have made sense?”
“You're right. It would have made sense. In fact, most of the structural proteins in what we now call the mitochondrial organelles are coded by nuclear-based genes. We believe that at least 300 of the nuclear genes were formerly mitochondrial genes that transferred.”
“But some didn't?”
“Those genes that stayed within the mitochondria are all, or nearly all, involved in the respiration of oxygen. Oxygen is an extremely toxic element. It's possible that it had to be handled within separately walled-off organelles to prevent its toxicity affecting the remainder of the living cell.”
“But wasn't oxygen always around, as part of the atmosphere?”
“No. Atmospheric oxygen is produced by plants and cyanobacteria. It is a by-product of their internal chemistry. We might recall that the early arrival of oxygen into Earth's atmosphere proved calamitous to many of the oceanic and shore-dwelling life-forms at that time. Only those who could breathe oxygen could survive its toxic presence. And even within the cells of those who inherited the mitochondrial ability to breathe oxygen, it had to be contained away from the delicate genomic machinery within the nucleus. It had to be locked away inside the original invading cells, the former bacteria that had now evolved into the mitochondrial organelles that were already resistant to the toxic effects of the oxygen.”
“Didn't we see something very similar with the viruses within the chromosomes?”
“We did! Those viruses that were expressing their genes as proteins appeared to retain their original genomic structure, including the controlling promoters.”
But to return to the use of mitochondrial genetics in paleontology, the uniquely maternal lineage of mitochondria has inevitably provided a powerful tool for evolutionary geneticists in exploring population genetics and the complex weave of human movement throughout history. Thus we are not surprised to discover that the D4h3a haplotype component that linked the Clovis child to his Siberian ancestors came from the study of Anzick-1's mitochondrial DNA.
As mentioned above, another equally powerful tool for population geneticists comes from the Y chromosome within the nuclear genome of males. Like the mitochondrial DNA and its exclusive link to the maternal genetic line, the Y chromosome is exclusively passed down from fathers to sons. Since it has no matching chromosome to recombine with during sexual recombination, it doesn't undergo the jumbling of bits from one chromosome to another. This provides a very useful means of following the pattern of key mutational haplotypes in different Y-chromosome populations over time. For example, in the case of the Clovis infant, Anzick-1, the “founding Q haplotype” on his Y chromosome was found to belong to subgroup L54*, which the geneticists predicted had separated out from another founding haplotype subgroup, M3, dating to approximately 16,900 years ago. This confirmed that Anzick-1 belonged to an ethnic population grouping that was closely related to the first humans to arrive into the Americas.
Just how accurate is this exploration of haplotypes and haplogroups? King Richard III of England was made infamous by the Shakespeare play that bears his name. The last of the Plantagenet dynasty, Richard was killed in the Battle of Bosworth Field on August 22, 1485, during the bloody War of the Roses. Shakespeare's play portrays Richard as a hunchbacked villain, who murdered his brother and two young nephews before attempting to marry his niece. But his supporters, including Philippa Langley of the Richard III Society, defended his reputation, claiming that Shakespeare had defamed Richard in support of the Tudor monarchs who had supplanted him and who reigned at the time when Shakespeare wrote his play.
In an exquisite story of detective sleuthing, Langley traced the historical records to find that Richard's remains had been buried, without coffin or dignity, in an Augustinian friary in the city of Leicester. Having obtained a small amount of funding, she persuaded the archeologists of the University of Leicester to conduct a dig in what was a present-day car park which was thought to overlie the former friary high altar. There they discovered a human skeleton that fit the historical descriptions of Richard. The skeleton was that of a man in his thirties with a severe curvature in his thoracic spine, known as a scoliosis—fitting Shakespeare's description of Richard's hunched back. It also showed signs of multiple wounds, indicating that the man had died in battle. Radiocarbon from two independent sources dated the bones to between 1430–1460 and 1412–1449. This seemed too early for Richard, but mass spectrometry carried out on the bones suggested that their owner had eaten a good deal of seafood, which can skew radiocarbon dating. A corrected date worked out at between 1475 and 1530, which would fit nicely with the historic date of Richard's death. However, uncertainties remained and, even with the location, the physical anatomy, and the radiocarbon dating, controversy still reigned as to whether Richard's remains had been found.
A new lin
e of genealogical research managed to identify a woman, Joy Ibsen (née Brown), who was a direct matrilineal descendant from Richard's mother. In genetic terms, Mrs. Ibsen should be carrying the same mitochondrial haplotype as Richard himself, but she had emigrated to Canada after the Second World War and died there in 2008. Fortunately she had given birth to a son, Michael, who was prepared to give a sample of his DNA for testing. The controversy was resolved when Michael Ibsen was found to share the rare mitochondrial haplotype J1c2c with the exhumed skeleton. There could no longer be any reasonable doubt that these were the bones of the last Plantagenet king.
As this genetic exploration of our human inheritance continues, we have become increasingly aware of how accurately our genome reflects hugely important movements and evolutionary events in our human ancestry and history. If some researchers are to be believed, we may even have discovered the genetic Adam and Eve.
Our obsession with fossils has distracted us from a much richer source of evolutionary information: genetic data…
LUIGI LUCA CAVALLI-SFORZA
We are all more closely related to one another than we might imagine, as a little thought experiment will quickly demonstrate. If we were to consider, say, four new generations of our ancestors per century, we can readily construct a branching tree with the numbers of ancestors doubling with each generation as we travel backward. Four grandparents descended from eight great-grandparents, who in turn descended from 16 great-great grandparents, and so on. Two centuries ago, or eight generations, we discover that we descended from some 256 multi-great ancestors living in that single generation. In four centuries the number rises to 65,536. In eight centuries the number rises to 4,294,967.296,—which is vastly more than the entire population of the world at that time—probably more people than had ever lived on Earth up to then. We need hardly go further back to realize that there is something seriously amiss with this line of thinking. Since we could not possibly have so many ancestors, there has to be another explanation.
The answer is simple: we all have a great many common ancestors. This can be explored at the genetic level by constructing haplotype trees, and it can be extended even wider geographically, and deeper into the past, if we construct haplogroup trees. The closer people are to one another, the more haplotypes and haplogroups they will have in common. And each distinguishing haplogroup is a marker—a genetic signpost—to a single ancestor in a specific place and a specific time who was the first to inherit the relevant Snip. From this haplogroup marker, specific population groups can be identified and their subsequent movements and migrations plotted.
The Italian geneticist Luigi Cavalli-Sforza, who was a professor at Stanford University, devoted his life to gathering this type of genetic information on different human populations. In his book Genes, Peoples and Languages, Cavalli-Sforza dismantled the idea of different races, arguing that the differences we saw between Africans, Asians, Europeans, and Australasians were superficial evolutionary adaptations to local conditions such as climate. Genetic studies of different peoples throughout the world have confirmed that we are all part of a single species, in which our commonalities overwhelm our differences. Archeological studies of fossilized bones, commonalities of tools, and the patterns of habitation and culture all point to the likelihood that our human ancestors originated in Africa, most likely sub-Saharan East Africa. These traditional archeological disciplines are now reaffirmed and augmented by genetic studies that allow us to gather much deeper perspectives on our human history than was possible before.
We have already glimpsed how specific clusters of mutations, known as Snips, in the mitochondrial genome and on the Y chromosome, enable geneticists to trace genetic haplotype and haplogroup lineages, and thus chart human population migrations, back into prehistoric times. Similar haplotypes and haplogroup lineages can be found in the 22 pairs of human chromosomes unallied to sexual differences, the so-called “autosomes,” enabling a third line of genetic tracing of human lineages and population movements. The distribution of specific endogenous retroviruses can be treated in the same way to locate the African origins of Homo sapiens and the subsequent global migrations of our species, which at this early stage are called “early modern humans.” The genomic viruses also have a role to play in such genetic determinations. For example, the distribution of two human-specific endogenous retroviruses, HERV-K113 and HERV-K115, are adding to the history.
Unlike most of the other HERVs, these two appear to have entered the genome after the primary migration of early modern humans out of Africa. Thus, while the great majority of HERVs are common to all of us, these two are found in a high percentage of present-day people who hail from East Africa, Arabia, and further east into Asia, but in low percentages, or not at all, in people hailing from Europe. To some geneticists, this suggests that there may have been more than one migration of modern humans out of Africa, perhaps with expansions and retreats that may have been precipitated by significant environmental or climate change.
As we have seen, mitochondrial genetics offers a series of mutational tags that make it possible to follow some of these complex population movements. Without the influence of evolutionary change, every daughter will inherit exactly the same mitochondrial genome from her mother, again and again, throughout all of history. If this were the case, my mitochondrial genome, inherited from my mother, would be identical to that of a common ancestor in Africa, say, 200,000 years ago. But we have seen how the mitochondrial genome has been altered by copying mistakes, or “mutations,” during the budding style of reproduction that mitochondria undergo. Sometimes these copying mistakes cause impairment of function of the mitochondrial genome, which would have very likely given rise to disease. But such pathological mutations would not become established as lineage markers because the resulting disease would result in reduced reproductive fitness. Only mutations that had no significant effect on reproductive fitness would have become incorporated as lineage markers. These have become part of haplotypes and haplogroups, which, having no effect on survival, are ignored by natural selection, so they survive unchanged over vast time periods.
Snips like this crop up at reasonably predictable intervals—a feature that enables geneticists to compare the numbers of mutations in a given stretch of the genome to a “molecular clock.” We have seen how key clusters of mutations in certain regions of the mitochondrial genome—haplotypes and haplogroups—can be linked to founder individuals, in place and time, then spread into the descendant population, allowing the migrations and movements of this population to be plotted in geography and time. Looked at from a different angle, differences between haplogroups are markers of different historic populations. And where we find, albeit rarely, a single haplogroup that is common to very many widely dispersed populations, this is seen as an important marker linking all these populations to a common founder ancestor.
What then if we were to discover a mitochondrial haplogroup that is common to every man and woman on Earth today? Would this not point to a woman who was a common ancestor of all of us—a genetic Eve?
In the 1980s, this was what a group of geneticists, led by Allan Wilson of the University of California, Berkeley, had in mind when, with the help of his doctoral students Mark Stoneking and Rebecca L. Cann, he conducted an examination of mitochondrial DNA from 147 Americans coming from a wide variety of racial and ethnic groupings. They were looking for evidence of shared and divergent haplogroups that would enable them to construct a hereditary tree for all of humanity. A decade earlier, Wilson had been joined by another pioneering geneticist, Wesley M. Brown, who had developed new techniques for screening mitochondrial DNA. Between them, these scientists discovered that mutation of mitochondrial DNA was 5–10 percent faster than in nuclear DNA. It was Wilson who first thought of the idea of the molecular clock, based on the fairly predictable occurrence of mutations in the human genome with time. Now they were convinced that they had the tools to investigate the potential of mitochondrial mutations as a measu
re of evolutionary relationships over time.
In the paper, Wilson and his colleagues figured that the global human population broke down into two broad mitochondrial haplogroups. One of these was confined to Africa; the other included some African groups as well as the rest of humanity. They drew several conclusions. For a start, it appeared to confirm the “out of Africa” theory, proposed by some paleoanthropologists for the origins of Homo sapiens, while contradicting the alternative “multi-regional theory,” which proposed that modern humans had not come directly out of Africa but had evolved over vast time periods in the major continents. It also supported what is now known as the “recent common origins” of modern humans, which proposes that all of the people on Earth today are part of a single, closely related population that emerged from Africa some time in the last 200,000 years. Their extrapolations went further; the African haplogroup had the greatest genetic diversity, a finding that has since been amply confirmed by other studies. There can be more genetic diversity, as defined by Snips, between neighboring African peoples, for example, across a major river, than we find across the entire Eurasian landmass. If we then consider that Snips arise through mutations at a fairly predictable rate over time, this implies that Homo sapiens has lived in Africa for far longer than anywhere else on Earth.
However, there was an additional, altogether surprising extrapolation. Wilson and colleagues also claimed that they had found genetic evidence for a female “last common ancestor” of modern humans—a woman in Africa who was the first to acquire the founder mitochondrial haplogroup mutation that is common to all of the people on Earth. They figured that this woman, dubbed by the media as “mitochondrial Eve,” contributed the common founder haplogroup to the human pedigree some time between 140,000 and 200,000 years ago. The idea of a mitochondrial Eve created front-page news headlines, proving both exciting and controversial at the time. It was, perhaps inevitably, misunderstood by many lay people, including religious groups, to imply that mitochondrial Eve was the single female ancestor of all of us.