It is now clear that when our ancestors left Africa, they mixed with the Neanderthals and Denisovans, archaic people who occupied Europe and Asia. The first offspring of those pairs would have had equal amounts of their two ancestral legacies: One chromosome in each pair would be modern human, the other archaic. But most of that archaic legacy is now gone, down to about two percent from the original 50. What happened?
People have considered a number of ideas. These range from the simple – a large and growing modern human population simply swamped the archaic genes – to more complex situations such as limited reproductive compatibility between the two genomes. But a new paper suggests something in between the two. Many Neanderthal genes may be somewhat harmful, the research suggests, but Neanderthal populations weren’t large enough to get rid of them.
It’s hard to understand the fate of Neanderthal genes because we have no idea how well the offspring of these matings fared. Everything indicates that the cases of successful crossing were rare (success defined here as offspring that also passed on their genes). As modern humans expanded into new areas and increased their populations accordingly, it may simply be that Neanderthal genes became diluted as their carriers continually mated with humans who were mostly or wholly modern.
But it’s also possible that the answer lies in the genome. There is clear evidence that some of the Neanderthal genes may be adaptive, helping modern humans live in a very different environment from the Africa they left. But it could also be that the chromosome structure or genes of Neanderthals limited the fertility of the hybrids. This would significantly speed up the dilution process described above. Alternatively, it could be that some Neanderthal genes influenced the health of the hybrids, making them slightly less fit than humans with more thoroughly modern genomes.
It is this last possibility that the new paper looks at. Several researchers at the University of California, Davis built a mathematical model to see what might happen to Neanderthal genes under different scenarios. These include varying degrees of dilution by modern human genomes, as well as varying degrees of evolutionary selection against Neanderthal genes.
The versions of the model that produced the best matches to the current genome suggest relatively rare gene variants (about one difference in every 10,000 bases) that were weakly selected by evolution. The strength of the selection against this is, in the words of the authors, “very low”. But given tens of thousands of years, it’s enough to reduce the amount of surviving Neanderthal DNA, though only by an average of 56 percent. Consistent with this suggestion, the amount of Neanderthal DNA also appears to be lower in gene-rich regions.
If the DNA was problematic, how did Neanderthals manage to spread through Europe and Asia in the middle of an ice age without getting rid of it? The Neanderthal genomes we looked at have very low diversity, meaning there aren’t many differences between them. This suggests that the Neanderthals’ effective population size was low and that evolution needs a significant effective population size to work. This is for purely practical reasons. To get rid of a harmful mutation, you need to replace it with a better variant; when the population is not diverse, chances are that there are no better variants.
The authors calculate that if the same level of selection were applied to Neanderthals, the genetic variants would be neutral in the smaller population. In other words, they would be invisible to evolutionary selection within the Neanderthal population. But they would generally not be invisible. The authors calculated that the genetic burden would radically reduce Neanderthals’ fitness compared to modern humans, which could help explain why they were quickly displaced as modern humans moved in.
In any case, the selection against Neanderthal DNA is not strong enough to completely eliminate the presence of their genes (as opposed to non-coding DNA) in modern humans. The authors estimate that there are currently about 7,000 deleterious Neanderthal alleles circulating in Eurasian populations, of which the average person has about 100. It is thus possible to actually test this mathematical model using more concrete data.
PLOS Genetics2016. DOI: 10.1371/journal.pgen.1006340 (About DOIs).