Thursday, April 22, 2021

Highly speculative: Evolution of genetic networks for human creativity

Evolution of genetic networks for human creativity. I. Zwir, C. Del-Val, M. Hintsanen, K. M. Cloninger, R. Romero-Zaliz, A. Mesa, J. Arnedo, R. Salas, G. F. Poblete, E. Raitoharju, O. Raitakari, L. Keltikangas-Järvinen, G. A. de Erausquin, I. Tattersall, T. Lehtimäki & C. R. Cloninger. Molecular Psychiatry, Apr 21 2021. https://www.nature.com/articles/s41380-021-01097-y

Abstract: The genetic basis for the emergence of creativity in modern humans remains a mystery despite sequencing the genomes of chimpanzees and Neanderthals, our closest hominid relatives. Data-driven methods allowed us to uncover networks of genes distinguishing the three major systems of modern human personality and adaptability: emotional reactivity, self-control, and self-awareness. Now we have identified which of these genes are present in chimpanzees and Neanderthals. We replicated our findings in separate analyses of three high-coverage genomes of Neanderthals. We found that Neanderthals had nearly the same genes for emotional reactivity as chimpanzees, and they were intermediate between modern humans and chimpanzees in their numbers of genes for both self-control and self-awareness. 95% of the 267 genes we found only in modern humans were not protein-coding, including many long-non-coding RNAs in the self-awareness network. These genes may have arisen by positive selection for the characteristics of human well-being and behavioral modernity, including creativity, prosocial behavior, and healthy longevity. The genes that cluster in association with those found only in modern humans are over-expressed in brain regions involved in human self-awareness and creativity, including late-myelinating and phylogenetically recent regions of neocortex for autobiographical memory in frontal, parietal, and temporal regions, as well as related components of cortico-thalamo-ponto-cerebellar-cortical and cortico-striato-cortical loops. We conclude that modern humans have more than 200 unique non-protein-coding genes regulating co-expression of many more protein-coding genes in coordinated networks that underlie their capacities for self-awareness, creativity, prosocial behavior, and healthy longevity, which are not found in chimpanzees or Neanderthals.


Discussion

This is the first study to identify the genotypic differences among chimpanzees, Neanderthals, and modern humans that may account for the rapid emergence of human creativity and other components of behavioral modernity, including its physical, emotional, cognitive, social, and spiritual features. In preparatory work we identified three naturally occurring genotypic networks for emotional reactivity, intentional self-control, and self-awareness. The 972 genes in these networks account for nearly all the heritable variation of human personality, including the characteristics of behavioral modernity (namely, creativity, prosocial behavior, and healthy longevity). Now we have found that 267 of these genes are absent in both chimpanzees and Neanderthal genomes, and we replicated this finding in three high-coverage Neanderthal genomes.

We also found that Neanderthals had nearly the same proportions of genes for emotional reactivity as chimpanzees. Excluding 54 genes found only in Sapiens, 72% of the 195 genes for emotional reactivity were common to all three species. On the other hand, Neanderthals were intermediate to chimpanzees and Sapiens in their proportions of genes for self-control and for self-awareness. Putting aside the genes for personality present in chimpanzees, Neanderthals had 33% of the genes for self-awareness and 37% of the genes for self-control that are present in Sapiens. Nevertheless, when we took into account the modular organization of these genes in clusters with other genes, we estimated the relative well-being of Neanderthal-like humans was 61–70% of that of prototypical Sapiens who carried genes found only in modern humans. Prototypical Sapiens have much stronger genotypic predisposition to the characteristics of behavioral modernity than Neanderthal-like humans, particularly from sets of genes in the self-awareness network associated with creativity, prosocial behavior, and longevity (F (3,252)p < 00001, Cohen’s effect size f = 0.34).

In addition, we obtained evidence that the genes found only in Sapiens were likely to be regulatory and advantageous. Specifically, 94% of the 267 genes found only in Sapiens were not protein-coding, including many lncRNAs (46%), pseudogenes (35%), and ncRNAs (6%). 64% of the genes found only in Sapiens were in the self-awareness network, especially lncRNAs that we found to be under positive selection.

Finally, we tested the importance of the genes unique to Sapiens for human well-being and behavioral modernity by identifying the brain regions in which they were over-expressed. We confirmed that naturally occurring clusters of genes associated with one or more genes found only in Sapiens were over-expressed in the core brain regions for human self-awareness, which is strongly associated with the human well-being, including the characteristics identified by anthropologists as distinguishing Sapiens from other hominids whom they replaced by 40 kya.

With these key findings in mind, we will discuss both the anthropological and the genetic data available to test our hypotheses related to the successive emergence of nearly disjoint networks for regulation of emotional reactivity, intentional self-control, and creative self-awareness in the hominoid lineage of modern humans. From our preparatory studies of the phenotypi–genotypic architecture of human personality, we recognize that these three networks function cooperatively so that a person can learn to integrate their habits, goals, and values in adapting to changes in their internal and external milieu. Available information about the coincident changes in brain and behavioral functioning in the phylogeny of Sapiens help to guide our interpretation of our findings based on comparison of the genomes of chimpanzees, Neanderthals, and Sapiens.

Emergence of the network for regulation of social emotions

The mammalian ancestors of anthropoid primates were mostly small, nocturnal, and solitary; but as temperatures cooled and tropical forests receded during the late Eocene, around 40 million years ago (mya), there was probably a selective advantage in social cooperation among higher primates as a protection against predators when foraging in the daytime [1214]. Social learning similar in kind to that of humans consequently developed among monkeys and apes, resulting in social attachment [9899] and the regulation of emotional reactivity based on social context and the reduction of emotional distress by reconciliation [100], as among chimpanzees today who, following a fight, often engage in mouth-to-mouth kissing and ventral embraces. Social learning also allows proto-cultural transmission of traditions in grooming, courting, foraging, and food preparation [101,102,103]. Emotional gestures and vocal calls facilitate social relations among triads and larger groups of higher primates, so that a third party, such as a high-ranking group leader, can intervene to resolve conflicts [100104].

On the other hand, while chimpanzees show emotional reactivity and learning abilities similar to those of a 2- or 3-year-old modern human child, they do not exhibit the regulatory capacities of older modern human children [105]. Chimpanzees use tools to solve simple tasks, like cracking nuts or catching termites; but they do not teach each other to manufacture and use these tools [1]. They can be taught to use signs and form two-to-four-word sentences at a rate consistent with behavioral conditioning, but, unlike modern human children, they do not spontaneously acquire symbolic language [45106107]. The self-aware memory of modern human children begins to mature around 4 years of age, and afterward they show greater capacity than chimpanzees for delay of gratification, reasoning about beliefs, and solving problems about internal memories [57105,106,107,108].

When the brains of higher primates are compared to those of more distant relatives of humans [1245], the prefrontal cortex is typically enlarged, projecting directly to the hypothalamus, striatum, thalamus, septum, and basal amygdala. Affective information is also relayed to the middle insular cortex, which allows regulation of sensuality. The mirror neuron system emerges, allowing the understanding of action and the imitation of observed behaviors, a necessary precursor of language. In great apes, there is also differentiation of the anterior insular cortex, allowing the enhanced emotional awareness that supports the communication of social emotions. On the basis of these findings of coincident changes in brain and behavior, we hypothesized that the genome of chimpanzees is likely to have the genetic network for regulation of emotional reactivity, but not those for either intentional self-control or creative self-awareness [1245]. Our current findings strongly confirm this hypothesis: the emotional reactivity network is well-developed in all three hominoid species that we evaluated. Putting aside the 54 genes found only in Sapiens, 72% of the 195 genes in the emotional reactivity network were shared by all three species (Table 1).

Emergence of the network for regulation of intentional self-control

Early hominins rapidly became distinguished from great apes by a greater facility for purposeful goal-seeking behaviors such as tool-making and coordinated hunting for food [1245]. Current indications are that the use and manufacture of stone tools were introduced by archaically-proportioned “australopiths” (e.g., [109]) at a time when open habitats were becoming more widespread as tropical forests shrank. Subsequently, the possession of more or less modern limb proportions by the earliest properly diagnosable members of the genus Homo indicates that hominins had finally committed themselves to those open habitats by a little under 2 million years ago. This crucial transition is poorly documented in behavioral terms, but it certainly represented an extreme environmental and economic shift that must have had profound cognitive and social sequelae.

Once committed to open habitats, the brain size of hominins began to increase rapidly. Homo ergaster (literally, working man) was reasonably tall and slenderly built in the basic manner of modern humans, and introduced the Acheulian tool industry of symmetrical bifacial hand-axes before 1.6 mya. These implements were intentionally flaked to conform to a template held in their makers’ minds. Later hominines continued this tool-making tradition without radical innovation until around 400 kya [910]. This archeological record of technological stasis for over a million years documents that early humans had the capacity for intentional self-control, but that humans living prior to 400 kya, including the common ancestor of Neanderthals and Sapiens, did not manifest the creativity associated with the genotypic network for self-awareness of Sapiens [12].

Homo neanderthalensis, a species that evolved from an endemic European precursor some 200 thousand years ago, was one highly evolved end-product of the human commitment to living in open habitats. Neanderthals were clearly purposeful and resourceful creatures who typically lived in small bands of perhaps 12–25 individuals that foraged across vast landscapes [110]. They were clearly sophisticated beings who were highly opportunistic in the resources they exploited: they hunted some frighteningly large prey when circumstances dictated (thereby possibly accounting for a reported high incidence of bone fractures [110]); at least occasionally they built shelters, and they controlled fire in hearths [111,112,113]. There is evidence at Shanidar cave in northern Iraq of a Neanderthal surviving to advanced age despite being severely handicapped by a useless arm, suggesting social cooperation and empathy for others within their small groups [113]. On the other hand, while Neanderthals buried their dead, they typically did so without the grave artifacts characteristic of later Cro-Magnon burials [113114]. Neanderthals produced artifacts that have been interpreted as symbolic art, but these infrequent expressions were simple and two-dimensional [73,74,75], possibly comparable to pictures produced by modern human children before the age of 7 years [115]. Their low genetic diversity suggests that they lived in small isolates with limited mating between groups [110116], although there is some evidence for female exogamy [115].

In the period following 40 thousand years ago the Neanderthals were rapidly replaced in Europe, albeit with some minor gene exchange [117], by invading Homo sapiens whose lives showed unprecedented cultural and technological sophistication. While still itinerant hunter-gatherers, these anatomically and behaviorally distinctive new humans populated the landscape in higher densities and brought with them the symbolic tradition of narrative cave art with use of pictorial depth cues in integrated compositions of great complexity and beauty [118]. This innovative practice of creating pictures from the imagination—“the mind’s eye”—is the most powerful indicator we have of the awakening of the modern sensibility, with its profusion of abstract but clearly meaning-laden signs in addition to the sophisticated animal images famous from such localities as Chauvet and Lascaux [73].

The brains of extinct humans are available only as fossil endocasts, limiting the observations that can be made. Compared to chimpanzees, fossil data document the emergence of hemispheric asymmetry along with bipedality in australopiths and non-Sapiens. Arising late in hominin history, Neanderthals had large brains that averaged about 1500 ml in volume, more or less identical to those of contemporaneous Pleistocene Homo sapiens (although modern human brains are almost 13% smaller [117]). However, those brains appear to have been organized differently from modern ones: Neanderthals had relatively larger visual areas, while Sapiens have expanded parietal lobes [69] and higher prefrontal regions. On the basis of these findings of coincident differences in brain and behavior, we hypothesized that the genome of Neanderthals would likely be found to have the genetic network for regulation of emotional reactivity and some of the genes of the network for intentional self-control, but not that for self-awareness [1245].

Our current findings confirm that the genotypic network for intentional self-control is well-developed in Neanderthals but not in chimpanzees. They also suggest that Neanderthals had acquired genes for self-control and self-awareness in numbers intermediate between modern human and chimpanzees. Excluding genes already present in chimpanzees, Neanderthals had 33% of the 254 genes for self-awareness and 37% of the 186 genes for self-control that are present in Sapiens. Taking into account the modular organization of groups of genes within human learning networks, we estimated that the relative level of genotypic predisposition to well-being and modernity of Neanderthal-like humans was 61–70% of that of prototypical Sapiens. When compared to prototypical Sapiens, the genotypic predisposition to modernity of Neanderthal-like humans is lowest for self-awareness (Cohen’s effect size f = 0.34). These findings suggest that the crucial event that sparked the emergence of behavioral modernity was the advanced evolution of the genotypic network for self-awareness in Sapiens, but we need to consider alternative explanations for these findings.

Of course, one possible alternative explanation is that all the genes present in Neanderthals may not have been documented in the genomic information currently available to us, even though we replicated our findings using the 2010 draft genome separately in each of the three high-coverage Neanderthal genomes that are available: Vindija 33.19 from the central range of Neanderthals in Croatia, as well as the genomes of a Neanderthal from the Altai Mountains and another from the Chagyrskaya Cave in Russia [110116117119]. These replicated findings provided robust support for our comparative analyses, but we still needed to know whether the genes we did find provided a mechanism that might account for the emergence of creativity.

Emergence of the network for creative self-awareness

What mechanism promoted the emergence of the genetic network for creative self-awareness in behaviorally modern human beings? The brains of Sapiens are unique in having a system for self-awareness that connects the late-myelinating regions of the frontal, parietal, and temporal cortices [57120]. These most recently evolved regions of the brain are the final association areas in which information is integrated and evaluated, and are linked into a unified network for episodic memory by projections from visual cortex [1245]. Autobiographical learning and memory mediate awareness of the self as a continuous identity across space and time. Psychologically, the creative network is so-named because it is found in people who are imaginative, inventive, prosocial, and spiritual [4247485580121]. Such self-transcendent thinking involves the ability to perceive oneself as a local aspect of a larger spatio-temporal whole, which permits thinking that is free and creative (i.e., “outside the box” of logical deduction and cultural tradition) and theoretically inductive (i.e., extrapolation beyond prior examples based on insight and creative imagination), as expressed in art, science, spirituality, and narrative syntactical language [1245]. On the basis of findings of the unique association of coincident changes in brain with cognitive functions for self-awareness and creativity, we hypothesized that only Sapiens were likely to have the genotypic network for self-awareness.

However, this hypothesis was only partially supported. We found that Neanderthals had only 33% of the genes for self-awareness present in Sapiens; but these genes, when organized in clusters with other human genes, were sufficient for Neanderthal-like humans to function at 61–70% of the level of well-being of prototypical Sapiens. This still does not inform us whether Neanderthals had crossed the genotypic threshold needed to have the potential to express some or all of the features of behavioral modernity, even if that capacity has not been adequately documented in the archeological record.

Therefore, we asked whether the genetic differences between Neanderthals and Sapiens revealed molecular mechanisms that qualitatively distinguished them and/or accounted for greater reproductive fitness in Sapiens. We found that the lincRNAs unique to Sapiens are under positive selection and are functionally different than those found in the Neanderthal genome. LincRNAs are known to evolve rapidly [122], and to influence complex patterns of adaptive functioning, plasticity, and health by regulation of gene expression [123124] and co-expression of groups of genes [125]. We found that 70% of the lincRNAs under positive selection and unique to Sapiens are in the genotypic network for self-awareness. When reared under conditions of parental warmth and tolerance, Sapiens with the genotypic network for self-awareness are likely to develop a creative-reliable personality profile characterized by creativity, altruism, and healthy longevity [19], thereby creating a distinctive social dynamic. This interpretation is directly supported by our additional finding that the genes for Sapiens are found in multi-locus genotypic clusters that are over-expressed in the brain regions that define the self-awareness network.

Furthermore, the characteristics of altruism and healthy longevity may have provided conditions necessary for kin selection for creativity in Sapiens as an adaptive response to intense ecological pressure from climatic fluctuations and unpredictable variability in resource availability in East Africa, but not Neanderthals who were not under the same pressures in Europe. The importance of prosocial environments for creative achievement is still evident in behavioral differences among modern humans observed today: even Sapiens with the genotypic network for self-awareness are still vulnerable to physical, emotional, cognitive, and social ill-being under hostile or inequitable social conditions [19], as shown in Figure S5D. Consequently, altruistic and creative behaviors are frequent, but inconsistent, features of Sapiens [121126].

Considering all the evidence available, we know that Neanderthals were intermediate between chimpanzees and Sapiens in the development of the genotypic network for self-awareness. We also know that Sapiens have a distinctive set of genes that are mostly in the self-awareness network, are under positive selection, and are not present in Neanderthals. Our genotypic findings document molecular mechanisms that may provide a likely explanation for the archeological record that has found only rudimentary evidence of creativity and other signs of behavioral modernity in Neanderthals. We, therefore, need to carefully consider these potentially crucial mechanisms in detail.

Hypotheses about selection for creativity

The newly emergent creativity may have provided selective advantages to behaviorally modern humans beyond its purely cognitive advantages. Physiologically, it is associated with enhanced memory functions, health, and well-being (Supplementary Figs. 5 and 6), including a predisposition to longevity and resilience against stress, injury, and chronic diseases including cardiovascular and neurodegenerative diseases [196465]. Living longer and healthier lives may have allowed behaviorally modern Homo sapiens to disperse rapidly and widely around the world, and it may also have helped individuals support their children, grandchildren, and others in interconnected social communities, thereby possibly leading to positive selection for traits such as creativity, innovativeness, prosociality, and wisdom [127,128,129,130,131]. We hypothesized that the genetic network for creativity was positively selected because we had previously found that longevity and well-being are promoted by the integration of creative functioning, plasticity, and virtues like moderation, altruism, and wisdom [19]. This hypothesis is further supported by our finding that 70% of the advantageous lncRNAs unique to Sapiens were in the self-awareness network, which is strongly associated with creativity, prosociality, and healthy longevity [195580]. Hence it is a crucial observation that most of the key regulatory genes for creative self-awareness are only present in Sapiens, and not in Neanderthals: of the 130 lncRNAs in the self-awareness network, none were present in chimpanzees, 42% were shared by Sapiens and Neanderthals, and 58% were found only in modern humans (Table 1, Fig. 2, Supplementary Table S3).

Role of LncRNAS in rapid evolutionary change

What mechanism can account for the rapidity of the evolution of creativity, healthy longevity, and fitness in Sapiens [1,2,3,4132]? Changes in mutation rates do not provide an explanation because they remained stable in the transition from archaic to modern humans [119133]. We considered mechanisms by which new genes appear in ways that do not depend on the mutation rate of ancestral genes [134]. We observed that 67% of the genes associated with human self-regulation and creativity were regulatory genes [64], including a significant predominance of lncRNA genes and pseudogenes when compared to the genes related to behavioral conditioning of temperament [65]. We know that differences in complexity of functions between species usually depend on differences in the regulation of gene expression of a highly conserved core of protein-coding genes, as has been shown for the differences between chimpanzees and humans [135,136,137].

More specifically, we know that lncRNA gene are often important regulators of gene expression [138] and are often acquired by horizontal gene transfer (HGT) [88]. HGT (i.e., the acquisition of genes from an organism other than a direct ancestor) allows genomes to expand rapidly, assemble new pathways, and express new functions [139]. HGT is the main mechanism for acquisition of new genes in prokaryotes and single-celled eukaryotes, and also is widespread in primates, including humans. Many new genes have been acquired throughout the modern human genome, especially protein-coding and lncRNA (e.g., lincRNA and antisense) genes [88]. Therefore, we tested the hypothesis that modern human beings acquired the genes that enabled the rapid evolution of creativity and healthy longevity by HGT. We found that genes for human personality are enriched in HGT regions, but the enrichment was observed for genes in the emotional reactivity network as well as the others. Furthermore, only 2 of the 39 genes we found in HGT regions were unique to modern humans. Therefore, we concluded that HGT may have contributed to personality development in hominoids in general, but it did not have a major role in the development of the creative personality or self-awareness.

In contrast, our findings that 70% of lincRNAs unique to humans and under positive selection were found exclusively in the self-awareness network does provide evidence of their involvement in the evolution of self-awareness and the various aspects of human well-being and behavioral modernity. Likewise 35% of the genes unique to Sapiens were pseudogenes, which are also often under positive selection in primates [140141] and involved in regulation of human cognition [142]. Pseudogenes were more frequent in genes associated with personality in Sapiens (8% of 972) than in Neanderthals (2% of 652). However, in Sapiens, pseudogenes were more frequent in the network for self-control (43%) than for self-awareness (28%). Therefore, lncRNAs appear to have played a more direct role in the emergence of creativity in Sapiens, although pseudogenes also contribute substantially to the differences between the two human species that emerged under distinct ecological conditions.

In contrast to the differences that we observed in biotypes between species, we found that the biotypes of the genes are similar for each of the three networks within each species (Fig. 1). In sum, both the differences in biotypes between species and the similarity of biotypes across adaptive networks within species support our hypothesis that the nearly disjoint genotypic networks are likely to have emerged in incremental steps. The initial emergence of intentional goal-setting in early hominins and later the emergence of the creative imagination of Sapiens has allowed modern humans to adapt to social and environmental challenges by brain functions that are associated with distinctive molecular processes and many regulatory genes that are found in modern humans, but not chimpanzees or Neanderthals.

Strengths and limitations

The major innovation and strength of our study of the evolution of human creativity is our having begun by first characterizing the complex genotypic–phenotypic architecture of human personality that underlies the human capacity for self-awareness, symbolism, and creativity. We identified and replicated the genotypic networks underlying the three major systems for learning in Sapiens (behavioral conditioning, intentionality, and self-awareness). This allowed us to focus comparative genomic analyses on 972 genes that account for modern human personality and learning capacities.

A major challenge was that there is less information about the Neanderthal genome than there is for modern Homo sapiens and chimpanzees. The annotated genome from the Neanderthal Genome Project from 2010 is based on low-coverage data, nearly all of which was from the Vindija Cave in Croatia that lay in the central range of Neanderthals throughout most of their existence. Fortunately, we were able to replicate our initial findings with the complete high-coverage (~50×) genome of the Altai Neanderthal, which confirmed the same 267 genes of Sapiens that were absent in Neanderthals from Vindija. Our findings were also confirmed in separate analyses of two other high-coverage (~30×) genomes from caves in both Croatia and Russia, so our findings are robust.

Another limitation of all work about complex phenotypes is that extinct hominids can never be available for quantitative phenotypic assessments comparable to those of modern humans using the TCI. Fortunately, the TCI has been directly validated with measures that correspond to descriptions of behavioral modernity by paleoanthropologists. Our genotypic measures and phenotypic measures are strongly related (Supplementary Fig. S3 and Table S2), and we have characterized the complex hierarchical and modular organization of their phenotypic–genotypic relations. As a result, we were able to use our genotypic measures to estimate the relative genotypic predisposition to the well-being and modernity of Neanderthal-like humans to prototypical Sapiens. Unfortunately, we still cannot state definitely what aspects of self-awareness Neanderthals may have displayed. We know that even chimpanzees have some rudimentary aspects of self-awareness, including mirror recognition and some recognition of self-agency [143]. However, chimpanzees lack flexibility in reasoning about abstractions, such as beliefs and intentions, an aspect of creativity and self-awareness that emerges between 3 and 5 years of age in modern human children [108144]. Therefore, we expect that Neanderthals had at least rudimentary aspects of self-awareness intermediate between chimpanzees and Sapiens, even though Neanderthals lacked most of the lncRNAs for self-awareness that we found in modern humans.

Because we focused only on the 972 genes that account for personality in Sapiens, we cannot exclude the possibility that Neanderthals had genes that were not present in Sapiens and influenced their personality and learning abilities. These genes could have been inherited from the common ancestor of Neanderthals and Sapiens or acquired by Neanderthals subsequently. Any such unique Neanderthal genes could have had functions homologous or distinct to those present in modern humans. However, we have identified what genes found in Sapiens, but not in Neanderthals, account for the emergence of the advantageous capacities of Sapiens, including creative self-awareness, prosocial behavior, and healthy longevity. Available behavioral data also indicate that these same capacities were absent in Neanderthals and other extinct hominids, and more detailed genotypic-phenotypic analyses comparable to what we have done in modern humans are impossible. Therefore, it is likely to be much more useful to pursue a more detailed understanding of the functions of the genes unique to Sapiens than those unique to extinct hominids.

Another major challenge was the limited information known about the functions of the non-coding RNA genes that comprised most of the genes found only in Sapiens. Fortunately, lncRNA genes have been shown to regulate the expression of sets of other genes, so we were able to identify the specific brain regions in which the multi-locus genotypes that map to the SNP sets related to self-awareness in Sapiens are expressed. Our findings of gene expression in the brain of the self-awareness network confirmed findings from functional brain imaging about the brain regions involved in various functions of self-awareness, including autobiographical memory, prospection, theory of mind, and the default mode [59]. Our findings extended this by revealing additional subcortical structures that are involved in cortical feedback loops important for the automatic processing and integration of information in self-awareness. The replicability of our genetic findings and their meaningful association with specific brain circuitry for complex human functions provides strong evidence for the validity of the data-driven methods we have developed and applied to characterize complex adaptive systems [64].

Overview

Our findings have broad implications for understanding what enabled Sapiens to displace Neanderthals and other species of Homo in the geologically recent past, as well as literally to reshape the world during the Anthropocene. Living longer, healthier lives may have promoted and valorized the extended periods of juvenile and adolescent learning that allow the accumulation of knowledge that is such a remarkable feature of behaviorally modern humans, and that is such an important factor in the economic success and complex social structures and relationships of Homo sapiens [145]. It may also have encouraged cooperation among individuals to promote the success of their children, grandchildren, and others in their extended communities [128131], enabling the technological innovativeness, behavioral flexibility, and exploratory disposition needed to allow Homo sapiens to spread throughout the world more successfully than other human lineages [1,2,3]. Further work is needed to understand the specific functions of the lncRNAs associated with self-awareness that underlie the capacity of modern humans for healthy longevity, prosociality, and creativity. Fuller understanding is greatly needed because of the frequent failure of these beneficial capacities of modern humans to be self-actualized during the Anthropocene [52].

External stressors brought on by COVID-19 were associated with sexual desire among people in relationships, in part due to reports of depressive symptoms

Balzarini, Rhonda N., Amy Muise, Giulia Zoppolat, Amanda N. Gesselman, Justin J. Lehmiller, Justin R. Garcia, Richard B. Slatcher, et al. 2021. “Sexual Desire in the Time of COVID-19: How Covid-related Stressors Are Associated with Sexual Desire in Romantic Relationships.” PsyArXiv. March 26. doi:10.31234/osf.io/nxkgp

Abstract: The COVID-19 pandemic and social distancing measures caused widespread social and economic disruptions, resulting in spikes in unemployment and financial instability, along with drastic changes to people's ability to feel socially connected. These changes could have implications on people’s sex lives as external stressors, like those introduced amidst the COVID-19 pandemic, are risk factors for depressive symptoms, which are associated with lower levels of sexual desire. The current research (N = 4,993) examined whether external stressors brought on by COVID-19 were associated with sexual desire among people in relationships (Studies 1-2), and whether this association was, in part, due to reports of depressive symptoms (Study 2). In the period immediately following the onset of the pandemic, more financial concern (Study 1) and worry (Study 2) were associated with higher sexual desire, while other factors, like stress (Studies 1-2), were associated with lower desire. We also followed a subset of participants every two weeks during the initial stages of the pandemic and at times when people reported greater stress, loneliness, financial strain, or worry than their average, they reported greater depressive symptoms, which, was in turn, associated with lower sexual desire. Results suggest that the social isolation and stress resulting from the COVID-19 pandemic has mixed associations with sexual desire at the onset of the pandemic. But over time, when people report heightened COVID-related stressors, like stress and loneliness, they tend to report lower sexual desire for their partner, in part because these stressors are associated with more depressive symptoms.


How the language you speak aligns to your genetic origins and may impact research on your health

Genetic substructure and complex demographic history of South African Bantu speakers. Dhriti Sengupta, Ananyo Choudhury, Cesar Fortes-Lima, Shaun Aron, Gavin Whitelaw, Koen Bostoen, Hilde Gunnink, Natalia Chousou-Polydouri, Peter Delius, Stephen Tollman, F. Xavier Gómez-Olivé, Shane Norris, Felistas Mashinya, Marianne Alberts, AWI-Gen Study, H3Africa Consortium, Scott Hazelhurst, Carina M. Schlebusch & Michèle Ramsay. Nature Communications volume 12, Article number: 2080. Apr 7 2021. https://www.nature.com/articles/s41467-021-22207-y

Popular version: How the language you speak aligns to your genetic origins and may impact research on your health (phys.org)

Abstract: South Eastern Bantu-speaking (SEB) groups constitute more than 80% of the population in South Africa. Despite clear linguistic and geographic diversity, the genetic differences between these groups have not been systematically investigated. Based on genome-wide data of over 5000 individuals, representing eight major SEB groups, we provide strong evidence for fine-scale population structure that broadly aligns with geographic distribution and is also congruent with linguistic phylogeny (separation of Nguni, Sotho-Tswana and Tsonga speakers). Although differential Khoe-San admixture plays a key role, the structure persists after Khoe-San ancestry-masking. The timing of admixture, levels of sex-biased gene flow and population size dynamics also highlight differences in the demographic histories of individual groups. The comparisons with five Iron Age farmer genomes further support genetic continuity over ~400 years in certain regions of the country. Simulated trait genome-wide association studies further show that the observed population structure could have major implications for biomedical genomics research in South Africa.

Discussion

More than 40 million South Africans speak one of the nine major South-Eastern Bantu languages as their first language. Notwithstanding clear divisions in the South-Eastern Bantu language phylogeny and geographic stratification of the speakers, very few studies have investigated the genetic differentiation between SEB groups. Based on a large-scale study of over 5000 participants representing eight of the nine major SEB groups in South Africa, we have demonstrated the presence of a robust fine-scale population structure within the SEB groups, which broadly separates genomes of SEB groups into the three major linguistic divisions (Nguni, Sotho-Tswana, and Tsonga), and also reflects the geographic distribution of LMAs to a large extent. The resolution of this structure within the SEB groups was enhanced considerably by taking ethno-linguistic concordance of individuals and their geographic locations into account. However, it needs to be noted that self-identity itself is complex, with about one third of the participants having more than one parent or grand-parent with a different ethnic self-identity. Moreover, while the PCA and PCA-UMAP shows clear population structure, there are exceptions highlighting the fluidity of cultural identity. Thus, self-selected group-identity encompasses significant group-related genetic variability, and it is important to emphasise that cultural identity and genetic variation are not necessarily aligned. Studies on population structure in South Africa should not be seen as justifying the ethnic nationalism generated by the country’s colonial and apartheid past. Our aim was to explore the role of genetic diversity in explaining population history and in health research. We recognise, and our study shows, that self-identity can involve considerable fluidity and that biological reductionist approaches pose dangers for the interpretation of our findings.

In alignment with results from previous studies10,32, our data also shows that differential Khoe-San gene flow plays a major role in the population structure of SEB groups. However, the persistence of the structure even after accounting for differential Khoe-San admixture suggests the contribution of other demographic factors in the genetic differentiation of these groups. The SEB groups start to show clear divergence in population size dynamics from about 40 generations ago. This timeframe converges with the earliest dates of Khoe-San admixture and probably points at the initiation of migration events that gradually separated these groups. On the other hand, a rather wide variation in Khoe-San admixture dates (spanning ~20 generations) among SEB groups possibly reflects the complexity of the settlement of different parts of the country by the ancestral BS populations. Comparison of present-day SEB groups with Iron-Age farmer genomes provided evidence for genetic continuity in a geographic region in Central-East South Africa for at least the last 300–500 years. Our results, while attesting to the well-known pattern of Khoe-San female-biased gene flow, showed notable differences in the extent of this bias among different SEB groups demonstrating that the nature of interaction between Khoe-San and BS could have varied temporally and geographically.

The dataset we generated for this study has provided a much better contextualization for previously sequenced Iron-Age genomes from Southern Africa. The SEB are unique in Africa, as being among the very few populations that contain considerable gene flow from the Khoe-San. These data therefore are of major importance in terms of understanding the interaction between the Khoe-San and other Southern African populations. They will play an important role in providing insights through comparative analyses once more genetic data from hunter-gatherers and ancient genomes from this geographic region become available.

Our analyses including allele frequency comparisons, genome-wide scans for selection and Khoe-San ancestry distribution show the SEB groups to be highly diverged at certain genomic regions. Based on simulated-trait GWAS, we further illustrate that the fine-scale population structure within the SEB groups could impact a GWAS by introducing a large number of false positives. A combination of cautious study design to minimize geographic and ethno-linguistic biases and stringent measures for population structure correction is therefore recommended for GWASs involving SEB groups. Moreover, while GWAS can address the false positives introduced due to population structure using genomic control, PC or other approaches, it is impossible to identify and control for population structure in candidate gene studies. Therefore, utmost care should be taken during study design to ethnically and geographically homogenise samples in order to control for false positives in association studies using limited markers.

A major limitation of our study is that the sampling sites do not cover the full geographic spread of SEB groups in the country, possibly causing some of the groups to be suboptimally represented in our dataset. Nevertheless, our results suggest that we are at a critical point in history where the population structure is still observable with efficient sampling and in-depth ethno-linguistic characterization, even if it is gradually diminishing due to migration and intermingling between different SEB groups. We hope that our findings will motivate studies with larger sample sizes and wider geographic representation to help unravel the demographic events that contributed to the peopling of South Africa.