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OBJECTIVE: Our primary objective was to investigate the variability of oxytocin (OT) and the GAMEN binding motif within the LNPEP oxytocinase in primates. MATERIALS AND METHODS: We sequenced the LNPEP segment encompassing the GAMEN motif in 34 Platyrrhini species, with 21 of them also sequenced for the OT gene. Our dataset was supplemented with primate sequences of LNPEP, OT, and the oxytocin receptor (OTR) sourced from public databases. Evolutionary analysis and coevolution predictions were made followed by the macroevolution analysis of relevant amino acids associated with phenotypic traits, such as mating systems, parental care, and litter size. To account for phylogenetic structure, we utilized two distinct statistical tests. Additionally, we calculated binding energies focusing on the interaction between Callithtrix jacchus VAMEN and Pro8OT. RESULTS: We identified two novel motifs (AAMEN and VAMEN), challenging the current knowledge of motif conservation in placental mammals. Coevolution analysis demonstrated a correlation between GAMEN, AAMEN, and VAMEN and their corresponding OTs and OTRs. Callithrix jacchus exhibited a higher binding energy between VAMEN and Pro8OT than orthologous molecules found in humans (GAMEN and Leu8OT). DISCUSSION: The coevolution of AAMEN and VAMEN with their corresponding OTs and OTRs suggests a functional relationship that could have contributed to specific reproductive and adaptive behaviors, including paternal care, social monogamy, and twin births, prominent traits in Cebidae species, such as marmosets and tamarins. Our findings underscore the coevolution of taxon-specific amino acids among the three studied molecules, shedding light on the oxytocinergic system as an adaptive epistatic repertoire in primates.

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Evidence indicates that oral microbiota plays a crucial role in human health and disease. For instance, diseases with multifactorial etiology, such as periodontitis and caries, which cause a detrimental impact on human well-being and health, can be caused by alterations in the host-microbiota interactions, where non-pathogenic bacteria give way to pathogenic orange/red-complex bacterial species (a change from a eubiotic to dysbiotic state). In this scenario, where thousands of oral microorganisms, including fungi, archaea, and phage species, and their host are co-evolving, a set of phenomena, such as the arms race and Red or Black Queen dynamics, are expected to operate. We review concepts on the subject and revisit the nature of bacterial complexes linked to oral health and diseases, as well as the problem of the bacterial resistome in the face of the use of antibiotics and what is the impact of this on the evolutionary trajectory of the members of this symbiotic ecosystem. We constructed a 16SrRNA tree to show that adaptive consortia of oral bacterial complexes do not necessarily rescue phylogenetic relationships. Finally, we remember that oral health is not exempt from health disparity trends in some populations, such as Native Americans, when compared with non-Indigenous people.

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Aquatic mammals (marine and freshwater species) share significant and similar adaptations, enabling them to tolerate hypoxia during regular breath-hold diving. Despite the established importance of HIF1A, a master regulator in the molecular mechanism of hypoxia response, and other associated genes, their role in the evolutionary adaptation of aquatic mammals is not fully understood. In this study, we investigated this topic by employing a candidate gene approach to analyze 11 critical genes involved in the HIF1A signaling pathway in aquatic mammals. Our gene analyses included evaluating positive and negative selection, relaxation or constriction of selection, and molecular convergence compared to other terrestrial mammals, including subterranean mammals. Evidence of selection suggested a significant role of negative selection, as well as relaxation of the selective regime in cetaceans for most of these genes. We found that the glutamine 68 variant in the HIF3α protein is unique to cetaceans and initial evaluations indicated a destabilizing effect on protein structure. However, further analyses are necessary to evaluate its functional impact and adaptive relevance in this taxon.

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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.

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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 Caatinga were 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.

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Preeclampsia is a multi-organ complication of pregnancy characterized by sudden hypertension and proteinuria that is among the leading causes of preterm delivery and maternal morbidity and mortality worldwide. The heterogeneity of preeclampsia poses a challenge for understanding its etiology and molecular basis. Intriguingly, risk for the condition increases in high-altitude regions such as the Peruvian Andes. To investigate the genetic basis of preeclampsia in a population living at high altitude, we characterized genome-wide variation in a cohort of preeclamptic and healthy Andean families (n = 883) from Puno, Peru, a city located above 3,800 meters of altitude. Our study collected genomic DNA and medical records from case-control trios and duos in local hospital settings. We generated genotype data for 439,314 SNPs, determined global ancestry patterns, and mapped associations between genetic variants and preeclampsia phenotypes. A transmission disequilibrium test (TDT) revealed variants near genes of biological importance for placental and blood vessel function. The top candidate region was found on chromosome 13 of the fetal genome and contains clotting factor genes PROZ, F7, and F10. These findings provide supporting evidence that common genetic variants within coagulation genes play an important role in preeclampsia. A selection scan revealed a potential adaptive signal around the ADAM12 locus on chromosome 10, implicated in pregnancy disorders. Our discovery of an association in a functional pathway relevant to pregnancy physiology in an understudied population of Native American origin demonstrates the increased power of family-based study design and underscores the importance of conducting genetic research in diverse populations.

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Our goal was to describe in more detail the evolutionary history of Gamma and two derived lineages (P.1.1 and P.1.2), which are part of the arms race that SARS-CoV-2 wages with its host. A total of 4,977 sequences of the Gamma strain of SARS-CoV-2 from Brazil were analyzed. We detected 194 sites under positive selection in 12 genes/ORFs: Spike, N, M, E, ORF1a, ORF1b, ORF3, ORF6, ORF7a, ORF7b, ORF8, and ORF10. Some diagnostic sites for Gamma lacked a signature of positive selection in our study, but these were not fixed, apparently escaping the action of purifying selection. Our network analyses revealed branches leading to expanding haplotypes with sites under selection only detected when P.1.1 and P.1.2 were considered. The P.1.2 exclusive haplotype H_5 originated from a non-synonymous mutational step (H3509Y) in H_1 of ORF1a. The selected allele, 3509Y, represents an adaptive novelty involving ORF1a of P.1. Finally, we discuss how phenomena such as epistasis and antagonistic pleiotropy could limit the emergence of new alleles (and combinations thereof) in SARS-COV-2 lineages, maintaining infectivity in humans, while providing rapid response capabilities to face the arms race triggered by host immuneresponses.

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Human Leukocyte Antigen (HLA)-G participates in several biological processes, including reproduction, vascular remodeling, immune tolerance, and hypoxia response. HLA-G is a potential candidate gene for high altitude adaptation since its expression is modulated in both micro and macro environment under hypoxia and constant cellular stress. Besides the promoter region, the HLA-G 3'untranslated region (UTR) influences HLA-G expression patterns through several post-transcriptional mechanisms. Currently, the 3'UTR genetic diversity in terms of altitude adaptation of Native American populations is still unexplored, particularly at high altitude ecoregions. Here, we evaluated 288 Native Americans from 9 communities located in the Andes [highland (HL); ≥2,500 m (range = 2,838-4,433 m)] and 8 populations located in lowland (LL) regions [<2,500 m (range = 80-431 m); Amazonian tropical forest, Brazilian central plateau, and Chaco] of South America. In total, nine polymorphic sites and ten haplotypes were observed. The most frequent haplotypes (UTR-1, UTR-2, and UTR-3) accounted for âˆ¼ 77% of haplotypes found in LL, while in the HL, the same haplotypes reach âˆ¼ 93%. Also, a remarkable high frequency of putative ancestral UTR-5 haplotype was observed in LL (21.5%), while in HL UTR-2 reaches up to 47%. Further, UTR-2 frequency positively correlates with altitude-related variables, while a negative correlation for UTR-5 was observed. From an evolutionary perspective, we observed a tendency towards balancing selection in HL and LL populations thus suggesting that haplotypes of ancient and more derived alleles may have been co-opted for relatively recent adaptations such as those experienced by modern humans in the highland and lowland of South America. We also discuss how long-term balancing selection can be a reservoir of genetic variants that can be positively selected. Finally, our study provides some pieces of evidence that HLA-G 3'UTR haplotypes may have contributed to high altitude adaptation in the Andes.

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STAT2 plays a strategic role in defending viral infection through the signaling cascade involving the immune system initiated after type I interferon release. Many flaviviruses target the inactivation or degradation of STAT2 as a strategy to impair this host's line of defense. Primates are natural reservoirs for a range of disease-causing flaviviruses (e.g., Zika, Dengue, and Yellow Fever virus), while rodents appear less susceptible. We analyzed the STAT2 coding sequence of 28 Rodentia species and 49 Primates species. Original data from 19 Platyrrhini species were sequenced for the SH2 domain of STAT2 and included in the analysis. STAT2 has many sites whose variation can be explained by positive selection, measurement by two methods (PALM indicated 12, MEME 61). Both evolutionary tests significantly marked sites 127, 731, 739, 766, and 780. SH2 is under evolutionary constraint but presents episodic positive selection events within Rodentia: in one of them, a moderately radical change (serine > arginine) at position 638 is found in Peromyscus species, and can be implicated in the difference in susceptibility to flaviviruses within Rodentia. Some other positively selected sites are functional such as 5, 95, 203, 251, 782, and 829. Sites 251 and 287 regulate the signaling mediated by the JAK-STAT2 pathway, while 782 and 829 create a stable tertiary structure of STAT2, facilitating its connection with transcriptional co-activators. Only three positively selected sites, 5, 95, and 203, are recognized members who act on the interface between STAT2 and flaviviruses NS5 protein. We suggested that due to the higher evolutionary rate, rodents are, at this moment, taking some advantage in the battle against infections for some well-known Flaviviridae, in particular when compared to primates. Our results point to dynamics that fit with a molecular evolutionary scenario shaped by a thought-provoking virus-host arms race.

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Prolactin (PRL) is a pleiotropic neurohormone secreted by the mammalian pituitary gland into the blood, thus reaching many tissues and organs beyond the brain. PRL binds to its receptor, PRLR, eliciting a molecular signaling cascade. This system modulates essential mammalian behaviors and promotes notable modifications in the reproductive female tissues and organs. Here, we explore how the intracellular domain of PRLR (PRLR-ICD) modulates the expression of the PRLR gene. Despite differences in the reproductive strategies between eutherian and metatherian mammals, there is no clear distinction between PRLR-ICD functional motifs. However, we found selection signatures that showed differences between groups, with many conserved functional elements strongly maintained through purifying selection across the class Mammalia. We observed a few residues under relaxed selection, the levels of which were more pronounced in Eutheria and particularly striking in primates (Simiiformes), which could represent a pre-adaptive genetic element protected from purifying selection. Alternative, new motifs, such as YLDP (318-321) and others with residues Y283 and Y290, may already be functional. These motifs would have been co-opted in primates as part of a complex genetic repertoire related to some derived adaptive phenotypes, but these changes would have no impact on the primordial functions that characterize the mammals as a whole and that are related to the PRL-PRLR system.

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