Variants unique to modern humans in over 70% of the population


Modern humans are characterized by their prosociality, a broad term that encompasses intra-species empathy, social tolerance, cooperation, and altruism. These facets of social cognition have been associated with variations in the genes for oxytocin and vasotocin (OT and VT) and their receptors (OTR and VTR). To shed light on the genetic basis of this behavior, scientists from the University of Barcelona (UB) and Rockefeller University conducted a new study comparing the available genomic sequences of these genes between modern humans, primate species. non-humans (e.g., chimpanzees, bonobos, and macaques) and, for the first time, archaic humans, using all available genomes from Neanderthals and Denisovans.

In the study published in the journal Comprehensive psychoneuroendocrinologyresearchers have identified several sites in which modern humans differed from both archaic humans and non-human primates, and others where modern and archaic humans differed from non-human primates.

“We used an interdisciplinary approach to understand the evolution of hominid prosociality through the lens of oxytocin and vasotocin receptors, where we combined evidence from modern and archaic genomics, population genetics , transcriptomics, and behavioral and neuroscientific studies, among other methods.These findings may shed light on the genetics underlying any identified sociality differences between modern and archaic humans, as well as similarities between behavior of modern humans and that of bonobos,” said first author Constantina Theofanopoulou. This research is part of her doctoral thesis carried out under the co-direction of Cedric Boeckx, ICREA researcher at the Institute UB Complex Systems (UBICS) and Erich D. Jarvis, professor at Rockefeller University.

Variants unique to modern humans in over 70% of the population

Considering the evidence on modern human prosociality and the involvement of oxytocin and vasotocin genes in social behaviors, the researchers hypothesized that the evolution of these genes could elucidate the genetic basis of the evolution of hominin prosociality. To this end, the study explored the differences between modern humans, archaic humans and non-human primates in polymorphic heterozygous sites in the human genome – locations where at least two alternative sequences are found in a population. “Previous studies comparing the entire modern human genome with Neanderthal or chimpanzee genomes have focused on fixed or nearly fixed changes in modern humans. This has led them to identify sites where, for example, all Neanderthals had adenine (one of the four nucleotides which together with guanine, cytosine and thymine make up DNA) and almost all modern humans (say, 98%) have guanine. study, we looked for differences in places where, by definition, not all modern humans share the same nucleotide, namely at polymorphic sites, where for example 70% of the modern human population has Adenine and 30% of Cytosine,” adds Theofanopoulou.

Researchers have identified five sites in oxytocin and vasotocin receptors where modern humans are unique in one of their two (or more) variants from archaic humans and non-human primates, and which are found at the same time in more than 70% of the modern human population. Then, they conducted functional and frequency analyzes to determine if the variants are relevant. They performed a series of analyzes at the five sites and found that some of the variants are highly functional, indicating that they have an effect on the molecular function of the proteins activated by these genes.

The researchers also found that these sites meet in regions of the genome that are active in the brain, particularly in the cingulate gyrus, a region of the brain involved in pathways related to social cognition. Additionally, all of these sites have been associated in other studies with a plethora of social behaviors or social deficits, such as autism, attention deficit hyperactivity disorder (ADHD), aggression, and more.

These findings may help explain some of the social differences between modern humans and what we assume we know about the social behaviors of Neanderthals and Denisovans. “For example, they might be relevant to the small social groups attributed to Neanderthals and Denisovans or to the decrease in modern human androgenization. They might also be relevant to a different social structure, that is, the Neanderthals have been linked to a polygynous social structure and higher male-male competition than most contemporary modern human populations,” explains Constantina Theofanopoulou.

Variants present only in modern and archaic humans

The study also found two sites on the oxytocin receptor under positive selection in modern and archaic humans: that is, modern and archaic humans exhibited a variant that was not present in any other primate not human. This means that these sites are found in very high percentages of the modern human population (in this case, over 85%). These same sites were also associated with a large number of behaviors or social deficits, and one of them was predicted as a highly functional site in their regulatory analyses. “Sites that are unique to both us and archaic humans relative to nonhuman primates may elucidate the genetic underpinnings of the progressive social tolerance necessary for the intensive cultural transmission of technological innovations (e.g., the use of fire ) in the evolution of mankind, as well as the reduction in aggression indicated by several markers of early hominid evolution, such as the reduction in size of male canids and accelerated demographic success,” adds Theofanopoulou. .

Sites converging with bonobos

Finally, the researchers found three sites where modern humans and bonobos, a species of primate that shows a convergence of prosocial behaviors with humans, have the same nucleotide. “Convergent sites in modern humans and bonobos could be insightful for understanding the putative similarities in prosociality, social tolerance, and cooperation between us and bonobos, and the differences of the two from chimpanzees. For example, bonobos outperform chimpanzees in tasks related to social causality or theory of mind and are more attentive to the face and eyes, suggesting greater empathic sensitivity,” notes the researcher.

All of the sites identified in this study have also been independently associated with disorders including social deficits, such as autism spectrum disorder (ASD). “Understanding developmental disorders through evolutionary lenses can help us achieve what we call an evo-devo (evolutionary and developmental biology) understanding of these disorders. If indeed ‘ontogenesis recapitulates phylogeny’, then deciphering our evolutionary trajectory can shed light on new genetic spots for clinical research which could, in turn, lead to earlier diagnosis of disorders”, underlines Constantina Theofanopoulou.

Future research in larger sample sizes

The next step in this research would be to test these results in larger sample sizes. This goal, as Theofanopoulou puts it, “is easier” to achieve in non-human primates such as chimpanzees and bonobos, but “is more difficult in the case of Neanderthals or Denisovans”, since access to genomes more archaic depends on archaeological finds, among other factors. “Another step is to broaden the scope of the search and include more oxytocin pathway genes, or other genes that have been highlighted in human evolution, such as dopamine,” concludes the researcher.


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