The recent emergence of SARS-CoV-2 is responsible for the current pandemic of COVID-19, which uses the human membrane protein ACE2 as a gateway to host-cell infection. We performed a comparative genomic analysis of 70 ACE2 placental mammal orthologues to identify variations and contribute to the understanding of evolutionary dynamics behind this successful adaptation to infect humans. Our results reveal that 4% of the ACE2 sites are under positive selection, all located in the catalytic domain, suggesting possibly taxon-specific adaptations related to the ACE2 function, such as cardiovascular physiology. Considering all variable sites, we selected 30 of them located at the critical ACE2 binding sites to the SARS-CoV-like viruses for analysis in more detail. Our results reveal a relatively high diversity of ACE2 between placental mammal species, while showing no polymorphism within human populations, at least considering the 30 inter-species variable sites. A perfect scenario for natural selection favored this opportunistic new coronavirus in its trajectory of infecting humans. We suggest that SARS-CoV-2 became a specialist coronavirus for human hosts. Differences in the rate of infection and mortality could be related to the innate immune responses, other unknown genetic factors, as well as non-biological factors.
COVID-19 pandemic represented a worldwide major challenge in different areas, and efforts undertaken by the scientific community led to the understanding of some of the genetic determinants that influence the different COVID-19 outcomes. In this paper, we review the studies about the role of human genetics in COVID-19 severity and how Brazilian studies also contributed to those findings. Rare variants in genes related to Inborn Errors of Immunity (IEI) in the type I interferons pathway, and its phenocopies, have been described as being causative of severe outcomes. IEI and its phenocopies are present in Brazil, not only in COVID-19 patients, but also in autoimmune conditions and severe reactions to yellow fever vaccine. In addition, studies focusing on common variants and GWAS studies encompassing worldwide patients have found several loci associated with COVID-19 severity. A GWAS study including only Brazilian COVID-19 patients identified a new locus 1q32.1 associated with COVID-19 severity. Thus, more comprehensive studies considering the Brazilian genomic diversity should be performed, since they can help to reveal not only what are the genetic determinants that contribute to the different outcomes for COVID-19 in the Brazilian population, but in the understanding of human genetics in different health conditions.
Sapajus libidinosus members of the Pedra Furada group, living in the Serra da Capivara National Park, use stone tools in a wider variety of behaviors than any other living animal, except humans. To rescue the evolutionary history of the Caatinga S. libidinosus and identify factors that may have contributed to the emergence and maintenance of their tool-use culture, we conducted fieldwork seasons to obtain biological samples of these capuchin monkeys. UsingCYTBsequences, we show a discrete but constant population growth from the beginning of the Holocene to the present, overlapping the emergence of the Caatinga biome. Our habitat suitability reconstruction reports the presence of plants whose hard fruits, seeds, or roots are processed by capuchins using tools. TheS. libidinosusindividuals in the Caatingawere capable of dynamically developing and maintaining their autochthonous culture thanks to: a) cognitive capacity to generate and execute innovation under selective pressure; b) tolerance favoring learning and cultural inheritance; c) an unknown genetic repertoire that underpins the adaptive traits; d) a high degree of terrestriality; e) presence and abundance of natural resources, which makes some places “hot spots” for innovation, and cultural diversification within a relatively short time.
The current study focuses on the investigation of AVPR2 (VTR2C) protein-coupled receptor variants specific to different primate taxa. AVPR2 is activated by the neurohormone AVP, which modulates physiological processes, including water homeostasis. Our findings reveal positive selection at three AVPR2 sites at positions 190, 250, and 346. Variation at position 250 is associated with human Congenital Nephrogenic Diabetes Insipidus (cNDI), a condition characterized by excessive water loss. Other 13 functional sites with potential adaptive relevance include positions 185, 202, 204, and 252 associated with cNDI. We identified SH3-binding motifs in AVPR2’s ICL3 and N-terminus domains, with some losses observed in clades of Cercopithecidae, Callitrichinae, and Atelidae. SH3-binding motifs are crucial in regulating cellular physiology, indicating that the differences may be adaptive. Co-evolution was found between AVPR2 residues and those in the AVP signal peptide/Neurophysin-2 and AQP2, other molecules in the same signaling cascade. No significant correlation was found between these Primates’ taxon-specific variants and the bioclimatic variables of the areas where they live. Distinct co-evolving amino acid sequences in functional sites were found in Platyrrhini and Catarrhini, which may have adaptive implications involving glucocorticoid hormones, suggesting varied selective pressures. Further studies are required to confirm these results.
23 May 2024 in American Journal of Biological Anthropology