The course of human history has been marked by complex patterns of migration, isolation, and admixture, the latter a term referring to the flow of genes between individuals from different populations. Admixture results in a mixture of genetic lineages, which leads to an increase in genetic diversity within a population. In addition to admixture among modern human groups, ancient humans interbred with other hominin groups, such as Neanderthals and Denisovans. This led to fragments of DNA from these ancient lineages being passed on to modern humans in a process known as introversion. Two recent studies have been published in Genome Biology and Evolution Studying mixing patterns in two different regions of the world- ; Africa and the Americas- ; To reveal how this process shaped the genome of modern humans.
Africa is the birthplace of mankind, where our species originated and diversified. For this reason, Africa contains the highest levels of genetic diversity and population structure among humans, with non-African populations largely representing a subset of the genetic variation found on the African continent. The genomes of Africans contain a mixture of multiple ancestors, each with a different evolutionary history. In an article titled “Evolutionary Genetics and Admixture in African Populations,” researchers from two institutes—Georgia Institute of Technology and Mediclinic Precise South Africa—review how multiple demographic events have shaped the African genome over time (Pfennig, et al. 2023). According to Joseph LaChance, one of the review’s authors, “What stands out is the enormous complexity of human demographic history, especially in Africa. There are many examples of population divergence followed by secondary contact, whose legacy is being written into our genome.”
For example, ancient introversion from ancient “ghost” groups of hominins that no longer exist contributed to approximately 4–6% of the ancestors of present-day Khoe-San, Mbuti, and West African populations. Recent demographic events over the past 10,000 years have led to similar admixture among modern humans, including gene flow between different groups of Khoe-San tap-speaking populations, the spread of pastoralism from eastern to southern Africa, and migrations of Bantu speakers across the continent.
Importantly, biomedical studies often fail to capture this diversity, which leads to implications for the health and disease of those of African descent. A better understanding of the genetic architecture could help predict disease risk in a population or even inform clinical decision-making of individual patients. Such information is essential for fair biomedical research, prompting the study authors to call for more ethically conducted studies of genetic diversity in Africa. “The crucial point now is the relative lack of African genetic data,” says Lachance. “Most genomic studies have focused on Eurasian populations, and this limitation can exacerbate existing health disparities.”
One way to better understand the genetic structure of the African genome is to study ancient DNA: “Going forward, it is expected that the analysis of ancient DNA will become more common. Future studies are also likely to focus on the exact population structure in Africa. However, no Logistical and financial hurdles remain, and there is a clear need for funding mechanisms that build research capacity in Africa.”
A second article was recently published in GBE, titled “The Impact of Modern Admixture on Archaic Human Ancestors in Populations,” focuses on admixture in the Americas (Whitt, et al. 2023), which were colonized by modern humans relatively recently. The first to enter the continent were the Native Americans who migrated from Siberia. The subsequent migration of Europeans and Africans due to European colonization and the transatlantic slave trade led to the mixing of populations that combined ancestors from different continents.
In this study, researchers from Brown University, the National Autonomous University of Mexico, and the University of California Merced analyzed how the resulting gene flow among modern humans redistributed the ancient ancestry in mixed genomes. They used data from the 1000 Genomes Project obtained from several mixed populations, including Colombians from Medellin, individuals of Mexican descent from Los Angeles, Peruvians from Lima, and Puerto Ricans from Puerto Rico. These genomes were compared to the high-coverage genomes of Neanderthals and Denisovans, ancient hominins that diverged from modern humans about 500,000 years ago and interbred with humans in Eurasia before becoming extinct around 40,000 years ago.
According to one of the study’s authors, Kelsey Witt of Brown University, these mixed groups have not been well studied compared to the more homogenous population. “It is common in studies like this for admixed populations to be excluded because multiple ancestry sources can make answering these questions more difficult. For this work, we wanted to focus on admixed populations to determine what we can learn from them, and whether mixed populations can Provide information about all lineage sources to which you have contributed.
The study found that the amount of introversion of Neanderthals and Denisovans was proportional to the amount of Native American or European ancestry in each group. Although European and Native American tracts in these mixed genomes have roughly equal proportions of Neanderthal variants, Denisovan variants are found primarily in Native American regions. This reflects a common ancestry between Native Americans and Asian populations, who also have higher levels of introgression to Denisovans.
Furthermore, by searching for archaic alleles present at high frequency in admixed American populations but low frequency in East Asian populations, the study authors identified several genes as candidates for adaptive introduction. These genes were involved in multiple pathways including immunity, metabolism, and brain development. Such findings have potential implications for the health of individuals in these mixed populations. “We’ve seen many examples of genetic mismatches in the literature, where some variants were adaptive at some point in the past, but in the current environment, they have a negative impact on health,” Witt says. In addition, in mixture groups may now interact “Populations and genetic variants that are unique to separate populations in unexpected (sometimes negative) ways when they are present in the same individual. Our work suggests that some archaic variants are specific to some ancestry sources and not others.”
Witt, like Lachance, knows more research is needed to continue deciphering the effects of the mixture on modern humans. “In many ways, mixed populations in the Americas are easy to study because we have a good idea of the timing and number of gene flow events,” Witt notes. “I would like to apply this work to other admixed populations, where we may not know when admixture occurred or which groups contributed to it, or in which cases the contributing populations are more closely related. I think the answers in these cases may not be entirely clear, but they may contribute in a better understanding of recent mix events.”
These studies show that admixture has played an important role in shaping human evolution, both in Africa and the Americas. Mixing not only re-shuffles genetic variation within and between populations, but also introduces new sources of variation that may have adaptive potential. By comparing the genomes of admixed groups with those of their ancestral groups and with those of ancient humans, these studies reveal how the mixing and matching of alleles shaped the evolution of our species.
Witt, K.E., et al. (2023) The effect of modern admixture on ancient human ancestry in human populations. Genome Biology and Evolution. doi.org/10.1093/gbe/evad066.