Mapping the genetic evolutionary timeline of human neural and cognitive traits

Abstract

Human evolution is characterised by extensive changes of body and brain, with perhaps one of the core developments being the fast increase in cranial capacity and brain volume. Paleontological records are the most direct method to study such changes, but they can unfortunately provide a limited view of how 'soft traits' such as brain function and cognitive abilities have evolved in humans. A potential complementary approach is to identify when particular genetic variants associated with human phenotypes (such as height, body mass index, intelligence, and also disease) have emerged in the 6-7 million years since we diverged from chimpanzees. In this study, we combine data from genome-wide association studies on human brain and cognitive traits with estimates of human genome dating. We systematically analyse the temporal emergence of genetic variants associated with modern-day human brain and cognitive phenotypes over the last five million years. Our analysis provides evidence that genetic variants related to neocortex structure (e.g., area, thickness; median evolutionary age = 400,170 years old), cognition (e.g., fluid intelligence; median age = 459,465), education (median age = 637,646), and psychiatric disorders (median age = 412,639) have emerged more recently in human evolution than expected by chance. In contrast, variants related to other physical traits, such as height (median age = 811,305) and body mass index (median age = 794,265), emerged relatively later. We further show that genes containing recent evolutionary modifications (from around 54,000 to 4,000 years ago) are linked to intelligence (P = 2 x 10-6) and neocortical surface area (P = 6.7 x 10-4), and that these genes tend to be highly expressed in cortical areas involved in language and speech (pars triangularis, P = 6.2 x 10-4). Elucidating the temporal dynamics of genetic variants associated with brain and cognition is another source of evidence to advance our understanding of human evolution. 2 bioRxiv preprint doi: https://doi.org/10.1101/2023.02.05.525539; this version posted September 28, 2023. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license. Main The human genome contains a footprint of our evolutionary history. Mapping the timeline of when specific genetic variants associated with modern-day phenotypes have emerged in our genome provides a unique window to examine the evolution of human features. This approach is particularly valuable for studying the evolutionary timeline of neural and cognitive traits1, which leave no direct physical traces in the fossil record. Human evolution involved dramatic changes to the brain and human cognitive abilities. Cranial capacity tripled over the past two million years of human evolution, a pace of encephalization that is unparalleled in other mammals2, with the neocortex being among the most expanded brain regions3. This expansion is widely believed to be one of the strongest catalysers for the development of complex behaviour and advanced cognition in the human lineage3–5. Human encephalization is thought to be the outcome of a wide range of natural (e.g. climate), nutritional (e.g. diet), and social (e.g. group size, parental care)6 selection pressures. These pressures have synergistically interacted with, and led to, modifications in the human genome at different periods across history7. In recent years, a rapidly growing number of Genome-Wide Association Studies (GWAS) have begun to unravel the genetic basis of modern human phenotypes8, and in this study we combined dating estimates for the emergence of variants in the human genome9 with these GWAS findings8 to map the genetic evolutionary timeline of human brain and cognitive abilities. We show that the emergence of genetic variants associated with core human attributes, such as brain morphology, cognition, and neuropsychiatric conditions, follows a distinctive temporal pattern, revealing recent genetic modifications in human evolution.