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Neanderthal Allele Fragment Size, Mutational Signatures Suggest Shorter European Generations

COLD SPRING HARBOR, NY (GenomeWeb) – Europeans may have had shorter historical generation times than other populations, according to a speaker at this year's Biology of Genomes meeting here. This shorter generation time may have affected the distribution of Neanderthal-derived allele fragments within the genomes of people of European ancestry as compared to people of East Asian ancestry.

Neanderthals interbred with modern non-African human populations about 50,000 years ago, but modern Europeans and modern East Asians harbor different-sized fragments of Neanderthal-derived DNA — over time, Neanderthal-derived alleles get broken down by recombination events. But this difference in fragment size between human populations has led some researchers to suggest there may have been two Neanderthal admixture pulses or back migration or even more complex interactions.

Aarhus University's Mikkel Schierup and his colleagues examined the distribution of Neanderthal-derived alleles within individuals from the Simons Diversity Project, comparing those lengths across various continental populations. Europeans, he reported at the conference, have shorter Neanderthal-derived fragments, but also harbor mutations indicative of young parents. Using this as a molecular clock, they estimated average generation times within these populations to find that, on average, Europeans had a five-year shorter generation time.

Schierup and his colleagues first examined the length of Neanderthal-derived fragments within all non-African individuals included in the SGDP panel dataset, where they uncovered systematic differences. They found a gradient of longer segments among more easterly populations. In particular, West Eurasian populations in the panel had a mean fragment length of 73 kilobases, while East Asian populations had a mean fragment length of 82 kilobases.

But when they modeled scenarios that may have led to the fragment size and allele patterns they observed, Schierup said he didn't think that a second Neanderthal admixture event occurred. Though such a two-pulse model would account for the longer fragment lengths observed among East Asians, it would also lead to an increase in the number of private alleles among East Asians, something they did not see.

Similarly, Schierup said backflow into Africa is also unlikely.

"We think … there was only one admixture event," he said.

Instead, Schierup noted that East Asians have segment lengths similar to what 7,000-year-old to 8,000-year-old Europeans had. This suggested to him that recombination may have occurred more slowly among East Asian populations. In particular, there may have been fewer generations among the East Asian population in the same time span during which recombination might have worked to break up the Neanderthal fragments into smaller pieces.

To bolster this idea, Schierup added that the mutational spectra of offspring can differ by parental age at conception. When they compared derived alleles among different continental populations — excluding SNPs also observed in African populations and after removing introgressed regions — he and his colleagues found that Europeans harbored a high number of cytosine-to-thymine transitions in a TCC context.

In a separate cohort, these types of C to T transitions have been linked to parental age.

How large these Neanderthal-derived alleles are can also provide insight into the time since the admixture event took place, as they act as a type of molecular clock. For each population, Schierup and his colleagues estimated the number of generations that have passed since the Neanderthal admixture event. They then used that to determine each population's average generation time over the past 54,000 years. From this, they found that while Native Americans, Central Asians, South Asians, and East Asians all had similar average generation times — about 32 years — Europeans had a shorter generation time — about 28 years.

This difference in generation times, Schierup noted, could be cultural and could be related to the adoption of agriculture in the region.

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