Not only did the sequencing of archaic genomes allow us to learn more about Neanderthals and Denisovans, it gave us important insights into our own evolution. Previously the human genome was only compared to our closest living relatives, the great apes, which helped us identify unique derived genomic changes that occurred since humans split from our last common ancestor with chimpanzees. Neanderthal and Denisovan genomes provide another set of comparative samples that might help us identify changes unique to modern humans that occurred after our split from the last common ancestor with Neanderthals/Denisovans. These changes may help account for our success as a species.
aDNA also provides insight into interactions between modern humans migrating out of Africa and other hominins that evolved in Europe and Asia. One of the hypotheses tested was this: if hybridization between modern humans and Neanderthals occurred, Neanderthals would have shared more genomic variants with some modern human populations than with others. When this was tested, the data showed that Neanderthals shared more genomic variants with Europeans and Asians than with African individuals (Sankararaman 2016). This difference in relatedness was significant, indicating that there had been hybridization between Neanderthals and modern humans.
From the genetic data, we know that Europeans have a smaller proportion of Neanderthal-derived genes than East Asians do (Prüfer et al. 2017). Thus, there was more admixture into ancestral East Asian populations than into ancestral European populations. Oceanians (Melanesians, Australian aborigines, and other Southeast Asian islanders) have a higher proportion of their DNA derived from Denisovans and longer stretches of Denisovan DNA. DNA in chromosomes get exchanged and experience genetic recombination, whereby introgressed regions (inherited from different species or taxon) are broken down into smaller segments each generation. Thus, longer stretches of introgressed DNA indicate that hybridization occurred more recently. Genetic analysis shows that the admixture event between the Denisovan and human ancestors of these populations is more recent than the admixture events between Neanderthals and modern humans.
To determine whether shared sequences are a result of introgression or more ancient substructure, researchers use divergence time: a measure of how long two sequences have been changing independently. The longer the two sequences have been changing independently, the more differences they will accumulate, which will result in a longer divergence time. By measuring the divergence time between the introgressed regions in modern human genomes and the Neanderthal sequences, researchers can calculate that the shared sequences are recent as well as date to when the two taxa made secondary contact. This is well after the initial population split between modern humans and Neanderthals. There has been gene flow from Neanderthals and Denisovans into modern human populations, between Neanderthals and Denisovans, and from modern humans into Neanderthals.
There is variation in how much of the Neanderthal genome is represented in the modern human population. Individuals outside of Africa usually have 1% to 4% of their genome derived from Neanderthals. Approximately 30% of the Neanderthal genome is represented in modern human genomes, altogether.
Introgressed genes have signatures that allow us to identify them and differentiate them from parts of the genome that are not introgressed. This can be identified in at least three ways. First, in this case, if the sequence is more similar to the Neanderthal sequence (i.e.,fewer sequence differences from the Neanderthal than the African modern human), it is likely that it is derived from a Neanderthal. Second, what is the divergence time between the allele and the same allele in a Neanderthal? If it is shorter than the divergence time between humans and Neanderthal, then the gene is most likely introgressed. An example of this can be seen in Figure D.2. Third, consider whether the allele that meets the first two criteria and is identified as possibly being introgressed can be found at higher frequencies in populations outside of Africa.
Examining the genomes of modern humans, we can see that there are regions of the genome with no Neanderthal and Denisovan genomic variants. These are known as Neanderthal or Denisovan introgression deserts. There are also overlaps between regions in the human genome that are Neanderthal and Denisovan deserts, which might indicate genomic incompatibilities between modern humans and these groups, resulting in those genes being selected against in the modern human genome. We can also infer that hybridization may itself have been a barrier to gene flow because there is a significant reduction in introgression on the X chromosome and around genes that are disproportionately expressed in the testes compared to other tissue groups. This could indicate that hybridization between modern humans and Neanderthals may have resulted in male hybrid infertility.
Because of the climate in Africa, it has been difficult or impossible to extract aDNA from African fossil remains. However, analysis of genomes of modern African populations indicate that there was admixture between modern humans and other hominins within Africa (see Figure D.2).
Another line of evidence concerns hybrids. A first-generation hybrid is called an F1 hybrid; it is the direct offspring of two lineages that have been evolving independently over an extended period. A second-generation hybrid (F2) would be the offspring of two F1 hybrids. A backcrossed individual is the result of an F1 or F2 hybrid mating with an individual from one of the parental populations. An example of a backcross would be when a Neanderthal-human hybrid produces offspring with a human; their offspring would be considered a first-generation backcrossed hybrid (B1). Sequencing of aDNA from fossil material has confirmed that hybridization between different hominins has occurred, supporting the introgression data from recent populations.
The sequencing of Oase 1, a suspected hybrid based on skeletal morphology, showed that it had a Neanderthal ancestor as recently as six to eight generations back. He would thus be considered a backcrossed individual. The recent sequencing of a 13-year-old Denisovan female showed that she was the F1 hybrid offspring of a Neanderthal mother (from whom she inherited Neanderthal mtDNA) and a Denisovan father. While these are only two examples of individuals who are confirmed hybrids, many other remains show some indication of gene flow between hominins.
We are continuing to learn how introgressed genes affect modern humans. Combining phenotypic and genetic information, Neanderthal-derived genes have been associated with diverse traits, ranging from thes skin’s sun sensitivity to excessive blood clotting by certain individuals. Interesting research has also shown that introgressed alleles might produce different gene expression profiles when compared to non-introgressed alleles. However, there is a lot of research still to be done to fully understand the effects of introgression on modern populations and how it might have assisted modern humans who migrated out of Africa.