Paleogenomics and the Tangled Web of Human Speciation

In previous posts in this series, we’ve sketched out the general outlines of hominin evolution – the hominins being those (extinct) species more closely related to us than to our closest living relative, the chimpanzee. And as we have seen, the hominin family tree was at one time diverse, with numerous species overlapping in both time and geographical distribution.

Of particular interest is the fact that this pattern of contemporaneous hominin species extends to humans: we coexisted with other hominin species for tens of thousands of years. The geographical and temporal overlap between humans and Neanderthals, for example, has long been known. What remained unknown – and highly contentious – was the question of interbreeding between humans and extinct hominin groups. Did humans and Neanderthals have children together? Did some of those children remain with human populations and become ancestors of some modern humans? Such questions are nearly impossible to address using only fossil remains (especially since Neanderthals and humans are so similar to begin with). Genetics, however, could provide a definitive answer – and developments in genomics technology would be the key to solving the puzzle.

The rise of (paleo)genomics

It’s sometimes difficult as a scientist to communicate with my friends just how rapidly the science of sequencing entire genomes has advanced over the last decade or so. When I was a graduate student in the late 1990s, even my model organism of choice (the lowly fruit fly, Drosophila melanogaster) had not yet had its genome completely sequenced. At that time, the human genome project was underway, but years from completion. Genome sequencing was the stuff of “big science”: large, well-funded groups spending millions upon millions of dollars to slowly piece together the data bit by painstaking bit.

Of course, when the scientific community makes such a significant investment it pays dividends far beyond the data itself: we also become much more technologically capable in the relevant area. In a decade, genome sequencing went from expensive, cutting-edge big science to an inexpensive, largely automated technique. Not only did genomics become much, much cheaper, it also became increasingly sensitive: we gained the ability to assemble genome data from ever smaller amounts of DNA.

Eventually, these advances would allow us to isolate and sequence DNA from extinct species. Amazingly as it sounds, in the proper conditions DNA can persist inside bones and teeth for tens (or even hundreds) of thousands of years. Given our interest in human evolution, DNA sequencing of Neanderthals was one of the first uses for this new technology – and for the first time we could test the hypothesis of interbreeding with genetic evidence.

All in the family – or not?

The first Neanderthal DNA to be sequenced was their mitochondrial DNA, which, as you may recall, is maternally inherited (i.e. passed down from mother to daughter, but not through males). These early studies found that Neanderthal mitochondrial DNA was not passed on into modern human populations. This in and of itself did not rule out the possibility of interbreeding, since mitochondrial DNA lineages can easily be lost in a population, and interbreeding involving male Neanderthals would not introduce Neanderthal mitochondrial DNA into human populations in the first place.

Later work sequencing Neanderthal chromosomal DNA would provide the definitive test, and the results were stunning: some modern human populations do have Neanderthal ancestry. As humans migrated out of Africa around 50,000 years ago, they encountered Neanderthals in what is now the Middle East. This encounter included (relatively rare) instances of interbreeding between the two groups. Moreover, we know that at least some of the children of human / Neanderthal matings remained within the human population, and went on to have children of their own. Today, traces of Neanderthal DNA can be found in all modern humans who are not of sub-Saharan African ancestry. Since sub-Saharan Africans descend from a population that did not encounter Neanderthals, they lack the characteristic Neanderthal DNA variation seen in other human populations.

More data, more evidence of interbreeding

Though the Neanderthal genome was first published in 2010, we have made significant advances in understanding patterns of hominin interbreeding even since then. One such advance was the discovery of a previously unknown hominin group, dubbed the Denisovans, which we know of from only a few finger bones and teeth. These meager remains were nonetheless able to provide a complete Denisovan genome sequence, and reveal them as a relative of Neanderthals. The Denisovan genome also revealed that they too contributed DNA to some modern human populations, specifically those of Melanesian descent.

Even more recent work has sequenced a high-quality Neanderthal genome. Though we have long had a relative abundance of Neanderthal remains, their DNA quality is poor. The discovery of Neanderthal remains in the same location that preserved the exceptional Denisovan DNA at last provided a very high quality Neanderthal genome, the analysis of which was published just this year. This new data allowed for several more robust analyses comparing human, Denisovan, and Neanderthal genomes. These analyses produced several noteworthy results: modern mainland Asian populations also have a small amount of Denisovan DNA; humans contributed some DNA variation to Neanderthals; Neanderthals and Denisovans interbred, with DNA variation flowing both ways; and (perhaps most interestingly) Denisovans have DNA variation that suggests they interbred with yet another archaic hominin group, possibly Homo erectus.

From these results, we can revisit the branching tree of hominin species and recognize that the pattern is not as simple as we have represented it. The general outline and relationships haven’t changed, but instead of clean divisions into separate lineages we now need to envision the branching pattern as more web like, with genetic exchange between what we previously represented as entirely distinct species. As we continue to find new hominin remains and (hopefully) sequence DNA from them, it is likely that the pattern will become even more webbed, adding detail and complexity. Just like a historian discovering ancient texts and exchange between ancient languages, so too we can now see the patchwork makeup of our own genome, and that of our close relatives.