Neanderthal-human interbreeding

Bruce Lahn is at it again. Earlier work from his lab showed that the microcephalin gene (MCPH1), which plays a role in brain development, has undergone strong selection in the last 40k years, with a new variant allele reaching a frequency of 70 percent in Eurasian populations. Shockingly to our politically correct thought police, the frequency in some other populations is much lower. Recent results (HHMI press release) imply that the origin of the advantageous variant allele dates back 1.1 million years, suggesting it may have entered the gene pool of modern humans via interbreeding with Neanderthals, already present in Eurasia when modern humans left Africa 40k years ago.

How do we know how old the advantageous allele is? I suppose you look at its detailed structure, and that of the other alleles. By using the roughly known mutation rate (base pair changes per unit time), you can estimate the time at which different versions diverged.

This was briefly covered in the Times today, but the article is lacking in detail. See here for more discussion.

Earlier studies by Lahn's group yielded evidence that the microcephalin gene has two distinct classes of alleles. One class, called the D alleles, is comprised of a group of alleles with rather similar DNA sequences. The other class is called the non-D alleles. Lahn and colleagues previously showed that all modern copies of the D alleles arose from a single progenitor copy about 37,000 years ago, which then increased in frequency rapidly and are now present in about 70 percent of the world's population. This rapid rise in frequency indicates that the D alleles underwent positive selection in the recent history of humans. This means that these alleles conferred a fitness advantage on those who possessed one of them such that these people had slightly higher reproductive success than people who didn't possess the alleles, said Lahn.

The estimate that all modern copies of the D alleles descended from a single progenitor copy about 37,000 years ago is based on the measurement of sequence difference between different copies of the D alleles. As a copy of a gene is passed from one generation to the next, mutations are introduced at a steady rate, such that a certain number of generations later, the descendent copies of the gene would on average vary from one another in DNA sequence by a certain amount. The greater the number of the generations, the more DNA sequence difference there would be between two descendent copies, said Lahn. The amount of sequence difference between different copies of a gene can therefore be used to estimate the amount of evolutionary time that has elapsed since the two copies descended from their common progenitor.

In the new studies reported in PNAS, the researchers performed detailed sequence comparisons between the D alleles and the non-D alleles of microcephalin. The scientists determined that these two classes of alleles have likely evolved in two separate lineages for about 1.1 million years — with the non-D alleles having evolved in the Homo sapiens lineage and the D alleles having evolved in an archaic, and now extinct, Homo lineage. Then, about 37,000 years ago, a copy of the D allele crossed from the archaic Homo lineage into humans, possibly by interbreeding between members of the two populations. This copy subsequently spread in humans from a single copy when it first crossed into humans to an allele that is now present in an estimated 70 percent of the population worldwide today.

The estimate of 1.1 million years that separates the two lineages is based on the amount of sequence difference between the D and the non-D alleles. Although the identity of this archaic Homo lineage is yet to be determined, the researchers argue that a likely candidate is the Neanderthals. The 1.1 million year separation between humans and this archaic Homo species is roughly consistent with previous estimates of the amount of evolutionary time separating the Homo sapiens lineage and the Neanderthal lineage, said Lahn. Furthermore, the time of introgression of the D allele into humans — about 37,000 years ago — is when humans and Neanderthals coexisted in many parts of the world.

Lahn said the group's data suggest that the interbreeding was unlikely to be a thorough genetic mixing, but rather a rare - and perhaps even a single — event that introduced the ancestral D allele previously present in this other Homo species into the human line.

“By no means do these findings constitute definitive proof that a Neanderthal was the source of the original copy of the D allele,” said Lahn. “However, our evidence shows that it is one of the best candidates. The timeline - including the introgression of the allele into humans 37,000 years ago and its origin in a lineage that separated with the human line 1.1 million years ago — agrees with the contact between, and the evolutionary history of, Neanderthals and humans.