Denisovians shaped the genome of modern Homo sapiens more than once

As detailed many times over the years on these GEITP pages, both fossil and genetic evidence indicate that Neanderthals (Homo neaderthalensis) and modern humans (Homo sapiens) evolved from a common ancestor between 500,000 and 200,000 years ago. Denisovans (Homo denisova; first fossil, the Altai individual, discovered in a cave in southeastern Russia) share a common ancestor with both modern humans and Neaderthals. This common ancestor (Homo heidelbergensis) most likely lived in Africa. Between 300,000 and 400,000 years ago, one group of Homo heidelbergensis migrated out of Africa, expanded into Eurasia and then split (near the Caucasus Mountains –– between the Black Sea and the Caspian Sea): Those that moved westward into Europe evolved into Neanderthals. Those that moved eastward into Asia became Denisovans. The human ancestors that remained in Africa evolved into our own species—Homo sapiens. Modern humans and Denisovans likely met for the first time in Eurasia (love at first sight?) ~40,000 to 60,000 years ago, after Homo sapiens had begun their own migration out of Africa.

Sequencing genomes of several early modern humans, Neanderthals, and Denisovans –– has confirmed that archaic hominins left their mark in the genomes of us modern humans. Present-day individuals in Eurasia have inherited ~2% of their genome from Neanderthals, and individuals from Oceania have inherited ~5% of their genome from Denisovans. Suggestive evidence indicates that admixture (inter-breeding of other hominins; again, love at first sight?) from other unidentified hominin species has also occurred in Africa. To understand the functional, phenotypic, and evolutionary consequences of archaic admixture –– it is necessary to identify the specific haplotypes (segments of DNA on one chromosome, having the same order of genes) and alleles (each gene has two alleles, one from each parent) that were inherited from, and then split from, archaic hominin ancestors. The S* approach is powerful for identifying introgressed haplotypes (in the absence of an archaic reference genome), because it leverages the unusual mutational characteristics of introgressed haplotypes.

Because of the long divergence time between Neanderthals and modern humans, Neanderthals carry many alleles that are specific to their lineage. Such alleles exist on introgressed haplotypes, but are absent or rare in African genomes. Furthermore, based on the recent timing of admixture, introgressed haplotypes are expected to be maintained without recombination over distances (DNA segments) of ~50,000 nucleotides (50 kb) on average, resulting in high levels of linkage disequilibrium (LD) between Neanderthal-specific alleles in non-African human genomes (LD is the non-random association of alleles at different loci in a given population).

In the [attached report] authors developed an S*-like method that has increased power and is suitable for large-scale genome-wide data. They applied the method to large sets of sequenced data from Eurasia and Oceania (the geographic region comprising Melanesia, Micronesia, Polynesia, and Australasia) in order to identify putative archaic-specific alleles (from Neaderthals and Denisovans, respectively). They examined the rate at which these alleles match the sequenced archaic genomes and the role of the genes containing these alleles –– to obtain insights into the history of admixture events and their impact on modern human genomes. They found Denisovan ancestry exists in populations from East and South Asia and Papuans. Denisovan ancestry comprises two components with differing similarity to the sequenced Altai Denisovan individual. This indicates that at least two distinct events of Denisovan admixture into modern humans occurred, involving Denisovan populations that had different levels of relatedness to the sequenced Altai Denisovan.

Cell Apr 2o18; 173: 53–61

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