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The rich diversity of morphology and behavior displayed across primate species provides an informative context in which to study the impact of genomic diversity on fundamental biological processes. Analysis of that diversity provides insight into long-standing questions in evolutionary and conservation biology, and is urgent given severe threats these species are facing. Here, we present high coverage whole-genome data from 233 primate species representing 86% of genera and all 16 families. This dataset was used, together with fossil calibration, to create a nuclear DNA phylogeny and to reassess evolutionary divergence times among primate clades. We found within-species genetic diversity across families and geographic regions to be associated with climate and sociality, but not with extinction risk. Furthermore, mutation rates differ across species, potentially influenced by effective population sizes. Lastly, we identified extensive recurrence of missense mutations previously thought to be human-specific. This study will open a wide range of research avenues for future primate genomic research.One-Sentence SummaryThe whole genome sequences of 233 primate species provide insight into the determinants of genetic diversity, phylogenomics, and human uniqueness.

INTRODUCTIONMillions of people have received genome and exome sequencing to date, a collective effort that has illuminated for the first time the vast catalog of small genetic differences that distinguish us as individuals within our species. However, the effects of most of these genetic variants remain unknown, limiting their clinical utility and actionability. New approaches that can accurately discern disease-causing from benign mutations and interpret genetic variants on a genome-wide scale would constitute a meaningful initial step towards realizing the potential of personalized genomic medicine.RATIONALEAs a result of the short evolutionary distance between humans and nonhuman primates, our proteins share near-perfect amino acid sequence identity. Hence, the effects of a protein-altering mutation found in one species are likely to be concordant in the other species. By systematically cataloging common variants of nonhuman primates, we aimed to annotate these variants as being unlikely to cause human disease as they are tolerated by natural selection in a closely related species. Once collected, the resulting resource may be applied to infer the effects of unobserved variants across the genome using machine learning.RESULTSFollowing the strategy outlined above we obtained whole-genome sequencing data for 809 individuals from 233 primate species and cataloged 4.3 million common missense variants. We confirmed that human missense variants seen in at least one nonhuman primate species were annotated as benign in the ClinVar clinical variant database in 99% of cases. By contrast, common variants from mammals and vertebrates outside the primate lineage were substantially less likely to be benign in the ClinVar database (71 to 87% benign), restricting this strategy to nonhuman primates. Overall, we reclassified more than 4 million human missense variants of previously unknown consequence as likely benign, resulting in a greater than 50-fold increase in the number of annotated missense variants compared to existing clinical databases.To infer the pathogenicity of the remaining missense variants in the human genome, we constructed PrimateAI-3D, a semisupervised 3D-convolutional neural network that operates on voxelized protein structures. We trained PrimateAI-3D to separate common primate variants from matched control variants in 3D space as a semisupervised learning task. We evaluated the trained PrimateAI-3D model alongside 15 other published machine learning methods on their ability to distinguish between benign and pathogenic variants in six different clinical benchmarks and demonstrated that PrimateAI-3D outperformed all other classifiers in each of the tasks.CONCLUSIONOur study addresses one of the key challenges in the variant interpretation field, namely, the lack of sufficient labeled data to effectively train large machine learning models. By generating the most comprehensive primate sequencing dataset to date and pairing this resource with a deep learning architecture that leverages 3D protein structures, we were able to achieve meaningful improvements in variant effect prediction across multiple clinical benchmarks. Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole-genome sequencing data for 809 individuals from 233 primate species and identified 4.3 million common protein-altering variants with orthologs in humans. We show that these variants can be inferred to have nondeleterious effects in humans based on their presence at high allele frequencies in other primate populations. We use this resource to classify 6% of all possible human protein-altering variants as likely benign and impute the pathogenicity of the remaining 94% of variants with deep learning, achieving state-of-the-art accuracy for diagnosing pathogenic variants in patients with genetic diseases.

Social adversity can increase the age-associated risk of disease and death, yet the biological mechanisms that link social adversities to aging remain poorly understood. Long-term naturalistic studies of nonhuman animals are crucial for integrating observations of social behavior throughout an individual’s life with detailed anatomical, physiological, and molecular measurements. Here, we synthesize the body of research from one such naturalistic study system, Cayo Santiago Island, which is home to the world’s longest continuously monitored free-ranging population of rhesus macaques. We review recent studies of age-related variation in morphology, gene regulation, microbiome composition, and immune function. We also discuss ecological and social modifiers of age-markers in this population. In particular, we summarize how a major natural disaster, Hurricane Maria, affected rhesus macaque physiology and social structure and highlight the context-dependent and domain-specific nature of aging modifiers. Finally, we conclude by providing directions for future study, on Cayo Santiago and elsewhere, that will further our understanding of aging across different domains and how social adversity modifies aging processes.

A defining feature of catarrhine primates is uniform trichromacy—the ability to distinguish red (long; L), green (medium; M), and blue (short; S) wavelengths of light. Although the tuning of photoreceptors is conserved, the ratio of L:M cones in the retina is variable within and between species, with human cone ratios differing from other catarrhines. Yet, the sources and structure of variation in cone ratios are poorly understood, precluding a broader understanding of color vision variability. Here, we report a large‐scale study of a pedigreed population of rhesus macaques (Macaca mulatta). We collected foveal RNA and analyzed opsin gene expression using cDNA and estimated additive genetic variance of cone ratios. The average L:M ratio and standard error was 1.03:1 ± 0.02. There was no age effect, and genetic contribution to variation was negligible. We found marginal sex effects with females having larger ratios than males. S cone ratios (0.143:1 ± 0.002) had significant genetic variance with a heritability estimate of 43% but did not differ between sexes or age groups. Our results contextualize the derived human condition of L‐cone dominance and provide new information about the heritability of cone ratios and variation in primate color vision.

The pygmy marmoset, the smallest of the anthropoid primates, has a broad distribution in Western Amazonia. Recent studies using molecular and morphological data have identified two distinct species separated by the Napo and Solimoes-Amazonas rivers. However, reconciling this new biological evidence with current taxonomy, i.e., two subspecies, Cebuella pygmaea pygmaea (Spix, 1823) and Cebuella pygmaea niveiventris (Lonnberg, 1940), was problematic given the uncertainty as to whether Spix’s pygmy marmoset (Cebuella pygmaea pygmaea) was collected north or south of the Napo and Solimoes-Amazonas rivers, making it unclear to which of the two newly revealed species the name pygmaea would apply. Here, we present the first molecular data from Spix’s type specimen of Cebuella pygmaea, as well as novel mitochondrial genomes from modern pygmy marmosets sampled near the type locality (Tabatinga) on both sides of the river. With these data, we can confirm the correct names of the two species identified, i.e., C. pygmaea for animals north of the Napo and Solimoes-Amazonas rivers and C. niveiventris for animals south of these two rivers. Phylogenetic analyses of the novel genetic data placed into the context of cytochrome b gene sequences from across the range of pygmy marmosets further led us to re-evaluate the geographical distribution for the two Cebuella species. We dated the split of these two species to 2.54 million years ago. We discuss additional, more recent, subdivisions within each lineage, as well as potential contact zones between the two species in the headwaters of these rivers.

Aging is accompanied by a host of social and biological changes that correlate with behavior, cognitive health and susceptibility to neurodegenerative disease. To understand trajectories of brain aging in a primate, we generated a multiregion bulk (N = 527 samples) and single-nucleus (N = 24 samples) brain transcriptional dataset encompassing 15 brain regions and both sexes in a unique population of free-ranging, behaviorally phenotyped rhesus macaques. We demonstrate that age-related changes in the level and variance of gene expression occur in genes associated with neural functions and neurological diseases, including Alzheimer’s disease. Further, we show that higher social status in females is associated with younger relative transcriptional ages, providing a link between the social environment and aging in the brain. Our findings lend insight into biological mechanisms underlying brain aging in a nonhuman primate model of human behavior, cognition and health.

There have been multiple published phylogenetic analyses of platyrrhine primates (New World monkeys) using both morphological and molecular data, but relatively few that have integrated both types of data into a total evidence approach. Here, we present phylogenetic analyses of recent and fossil platyrrhines, based on a total evidence data set of 418 morphological characters and 10.2 kilobases of DNA sequence data from 17 nuclear genes taken from previous studies, using undated and tip-dating approaches in a Bayesian framework. We compare the results of these analyses with molecular scaffold analyses using maximum parsimony and Bayesian approaches, and we use a formal information theoretic approach to identify unstable taxa. After a posteriori pruning of unstable taxa, the undated and tip-dating topologies appear congruent with recent molecular analyses and support largely similar relationships, with strong support for Stirtonia as a stem alouattine, Neosaimiri as a stem saimirine, Cebupithecia as a stem pitheciine, and Lagonimico as a stem callitrichid. Both analyses find three Greater Antillean subfossil platyrrhines (Xenothrix, Antillothrix, and Paralouatta) to form a clade that is related to Callicebus, congruent with a single dispersal event by the ancestor of this clade to the Greater Antilles. They also suggest that the fossil Proteropithecia may not be closely related to pitheciines, and that all known platyrrhines older than the Middle Miocene are stem taxa. Notably, the undated analysis found the Early Miocene Panamacebus (currently recognized as the oldest known cebid) to be unstable, and the tip-dating analysis placed it outside crown Platyrrhini. Our tip-dating analysis supports a late Oligocene or earliest Miocene (20.8-27.0 Ma) age for crown Platyrrhini, congruent with recent molecular clock analyses.

The pygmy marmoset, the smallest of the anthropoid primates, has a broad distribution in Western Amazonia. Recent studies using molecular and morphological data have identified two distinct species separated by the Napo and Solimões-Amazonas rivers. However, reconciling this new biological evidence with current taxonomy, i.e., two subspecies, Cebuella pygmaea pygmaea (Spix, 1823) and Cebuella pygmaea niveiventris (Lönnberg, 1940), was problematic given the uncertainty as to whether Spix’s pygmy marmoset (Cebuella pygmaea pygmaea) was collected north or south of the Napo and Solimões-Amazonas rivers, making it unclear to which of the two newly revealed species the name pygmaea would apply. Here, we present the first molecular data from Spix’s type specimen of Cebuella pygmaea, as well as novel mitochondrial genomes from modern pygmy marmosets sampled near the type locality (Tabatinga) on both sides of the river. With these data, we can confirm the correct names of the two species identified, i.e., C. pygmaea for animals north of the Napo and Solimões-Amazonas rivers and C. niveiventris for animals south of these two rivers. Phylogenetic analyses of the novel genetic data placed into the context of cytochrome b gene sequences from across the range of pygmy marmosets further led us to re-evaluate the geographical distribution for the two Cebuella species. We dated the split of these two species to 2.54 million years ago. We discuss additional, more recent, subdivisions within each lineage, as well as potential contact zones between the two species in the headwaters of these rivers.

Survival at high altitude requires adapting to extreme conditions such as environmental hypoxia. To understand high-altitude adaptations in a primate, we assembled the genome of the gelada (Theropithecus gelada), an endemic Ethiopian monkey, and complemented it with population resequencing, hematological, and morphometric data. Unexpectedly, we identified a novel karyotype that may contribute to reproductive isolation between gelada populations. We also identified genomic elements including protein-coding sequences and gene families that exhibit accelerated changes in geladas and may contribute to high-altitude adaptation. Our findings lend insight into mechanisms of speciation and adaptation while providing promising avenues for functional hypoxia research.

[Background] An individual’s microbiome changes over the course of its lifetime, especially during infancy, and again in old age. Confounding factors such as diet and healthcare make it difficult to disentangle the interactions between age, health, and microbial changes in humans. Animal models present an excellent opportunity to study age- and sex-linked variation in the microbiome, but captivity is known to influence animal microbial abundance and composition, while studies of free-ranging animals are typically limited to studies of the fecal microbiome using samples collected non-invasively. Here, we analyze a large dataset of oral, rectal, and genital swabs collected from 105 free-ranging rhesus macaques (Macaca mulatta, aged 1 month-26 years), comprising one entire social group, from the island of Cayo Santiago, Puerto Rico. We sequenced 16S V4 rRNA amplicons for all samples., [Results] Infant gut microbial communities had significantly higher relative abundances of Bifidobacterium and Bacteroides and lower abundances of Ruminococcus, Fibrobacter, and Treponema compared to older age groups, consistent with a diet high in milk rather than solid foods. The genital microbiome varied widely between males and females in beta-diversity, taxonomic composition, and predicted functional profiles. Interestingly, only penile, but not vaginal, microbiomes exhibited distinct age-related changes in microbial beta-diversity, taxonomic composition, and predicted functions. Oral microbiome composition was associated with age, and was most distinctive between infants and other age classes., [Conclusions] Across all three body regions, with notable exceptions in the penile microbiome, while infants were distinctly different from other age groups, microbiomes of adults were relatively invariant, even in advanced age. While vaginal microbiomes were exceptionally stable, penile microbiomes were quite variable, especially at the onset of reproductive age. Relative invariance among adults, including elderly individuals, is contrary to findings in humans and mice. We discuss potential explanations for this observation, including that age-related microbiome variation seen in humans may be related to changes in diet and lifestyle., This work was supported by an AAPA Cobb Professional Development Award and a postdoctoral fellowship from the Alberta Children’s Hospital Research Institute to MCJ. MCJ was funded by a grant from the Natural Sciences and Engineering Research Council (NSERC) to ADM and by the Natural Environment Research Council (NERC, NE/T000341/1). Microbiome sampling was supported by NYU and a Leakey Foundation grant to JPH and SCA. Computational resources were provided by WestGrid and Compute Canada. The Caribbean Primate Research Center (CPRC) is supported by the National Institutes of Health. An Animal and Biological Material Resource Center Grant (P40OD012217) was awarded to UPR from the Office of Research Infrastructure Programs (ORIP), and a Research Facilities Construction Grant (C06OD026690) was awarded for the renovation of CPRC facilities after Hurricane Maria. MJM and MLP are supported by NIH NIMH R01MH96875 and R01MH118203. AET was supported by a Ford Foundation Fellowship. This work was partially supported by the Canadian Institute for Advanced Research (CIFAR), to MGDB.

Versión preprint disponible en: http://hdl.handle.net/10261/229066, The novel coronavirus SARS‐CoV‐2, which in humans leads to the disease COVID‐19, has caused global disruption and more than 2 million fatalities since it first emerged in late 2019. As we write, infection rates are at their highest point globally and are rising extremely rapidly in some areas due to more infectious variants. The primary target of SARS‐CoV‐2 is the cellular receptor angiotensin‐converting enzyme‐2 (ACE2). Recent sequence analyses of the ACE2 gene predict that many nonhuman primates are also likely to be highly susceptible to infection. However, the anticipated risk is not equal across the Order. Furthermore, some taxonomic groups show high ACE2 amino acid conservation, while others exhibit high variability at this locus. As an example of the latter, analyses of strepsirrhine primate ACE2 sequences to date indicate large variation among lemurs and lorises compared to other primate clades despite low sampling effort. Here, we report ACE2 gene and protein sequences for 71 individual strepsirrhines, spanning 51 species and 19 genera. Our study reinforces previous results while finding additional variability in other strepsirrhine species, and suggests several clades of lemurs have high potential susceptibility to SARS‐CoV‐2 infection. Troublingly, some species, including the rare and endangered aye‐aye (Daubentonia madagascariensis), as well as those in the genera Avahi and Propithecus, may be at high risk. Given that lemurs are endemic to Madagascar and among the primates at highest risk of extinction globally, further understanding of the potential threat of COVID‐19 to their health should be a conservation priority. All feasible actions should be taken to limit their exposure to SARS‐CoV‐2., ADM is supported bythe Natural Sciences and Engineering Research Council of Canada(NSERC Discovery Grant) and Canada Research Chairs Program.MCJ's postdoctoral appointment is supported by funding from theNatural Environment Research Council (NERC NE/T000341/1). IGand MG acknowledge the support of the Spanish Ministry of Scienceand Innovation through the Instituto de Salud Carlos III and the2014–2020 Smart Growth Operating Program, to the EMBL part-nership and cofinancing with the European Regional DevelopmentFund (MINECO/FEDER, BIO201571792P). We also acknowledgethe support of the Centro de Excelencia Severo Ochoa, and theGeneralitat de Catalunya through the Departament de Salut, De-partament d'Empresa i Coneixement and the CERCA Programme.TMB is supported by funding from the European Research Council(ERC) under the European Union's Horizon 2020 research and in-novation program (grant agreement No. 864203), BFU201786471P (MINECO/FEDER, UE), “Unidad de Excelencia María de Maeztu”,funded by the AEI (CEX2018000792M), Howard Hughes Interna-tional Early Career, Obra Social "La Caixa" and Secretaria d'Uni-versitats i Recerca and CERCA Programme del Departamentd'Economia i Coneixement de la Generalitat de Catalunya (GRC2017 SGR 880). PSA thanks the National Institutes of Health(R35GM130333) for financial support. EL is supported by CGL201782654P (MINECO/FEDER, UE). EDJ and OF's contributions weresupported by funds from Howard Hughes Medical Institute and theRockefeller University. Chris Smith drew the images for Figure 1. Theauthors would like to thank the Veterinary and Zoology staff atWildlife Reserves Singapore for their help in obtaining the tissuesamples, as well as the Lee Kong Chian Natural History Museum forstorage and provision of the tissue samples. Finally, we thank tworeviewers for quick and constructive comments, and Karen Bales forher supportive editorial oversight

Ecological flexibility, extended lifespans, and large brains have long intrigued evolutionary biologists, and comparative genomics offers an efficient and effective tool for generating new insights into the evolution of such traits. Studies of capuchin monkeys are particularly well situated to shed light on the selective pressures and genetic underpinnings of local adaptation to diverse habitats, longevity, and brain development. Distributed widely across Central and South America, they are inventive and extractive foragers, known for their sensorimotor intelligence. Capuchins have among the largest relative brain size of any monkey and a lifespan that exceeds 50 y, despite their small (3 to 5 kg) body size. We assemble and annotate a de novo reference genome for Cebus imitator. Through high-depth sequencing of DNA derived from blood, various tissues, and feces via fluorescence-activated cell sorting (fecalFACS) to isolate monkey epithelial cells, we compared genomes of capuchin populations from tropical dry forests and lowland rainforests and identified population divergence in genes involved in water balance, kidney function, and metabolism. Through a comparative genomics approach spanning a wide diversity of mammals, we identified genes under positive selection associated with longevity and brain development. Additionally, we provide a technological advancement in the use of noninvasive genomics for studies of free-ranging mammals. Our intra- and interspecific comparative study of capuchin genomics provides insights into processes underlying local adaptation to diverse and physiologically challenging environments, as well as the molecular basis of brain evolution and longevity., Funding was provided by Washington University in St. Louis, the Canada Research Chairs Program, and a National Sciences and Engineering Research Council of Canada Discovery Grant (to A.D.M.); the Alberta Children’s Hospital Research Institute (A.D.M., J.D.O., and M.C.J.); the Beatriu de Pinós postdoctoral programme of the Government of Catalonia’s Secretariat for Universities and Research of the Ministry of Economy and Knowledge 2017 BP 00265 (to J.D.O.); and the Japan Society for the Promotion of Science 15H02421 and 18H04005 (to S.K.). This work was partly funded by a Methuselah Foundation grant (to J.P.d.M.); and the Comisión Nacional de Investigación Científica y Tecnológica Chile through the doctoral studentship number 21170433 and the scholarship from the Higher Education Quality Improvement Program (MECESUP) AUS 2003 (to D.T.-M.). GenAge is funded by a Biotechnology and Biological Sciences Research Council Grant BB/R014949/1 (to J.P.d.M.). T.M.-B. is supported by funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 864203), BFU2017-86471-P (MINECO/FEDER, UE), “Unidad de Excelencia María de Maeztu”, funded by the Agencia Estatal de Investigación (CEX2018-000792-M), Howard Hughes International Early Career, Obra Social “La Caixa” and Secretaria d’Universitats i Recerca and CERCA Programme del Departament d’Economia i Coneixement de la Generalitat de Catalunya (GRC 2017 SGR 880). C.F. is supported by the “La Caixa” doctoral fellowship program. E.L. is supported by CGL2017-82654-P (MINECO/FEDER, UE). M.C.J. is supported by funding from the Natural Environment Research Council (NE/T000341/1)., With funding from the Spanish government through the "Severo Ochoa Centre of Excellence" accreditation (CEX2018-000792-M).

The emergence of SARS-CoV-2 has caused over a million human deaths and massive global disruption. The viral infection may also represent a threat to our closest living relatives, nonhuman primates. The contact surface of the host cell receptor, ACE2, displays amino acid residues that are critical for virus recognition, and variations at these critical residues modulate infection susceptibility. Infection studies have shown that some primate species develop COVID-19-like symptoms; however, the susceptibility of most primates is unknown. Here, we show that all apes and African and Asian monkeys (catarrhines), exhibit the same set of twelve key amino acid residues as human ACE2. Monkeys in the Americas, and some tarsiers, lemurs and lorisoids, differ at critical contact residues, and protein modeling predicts that these differences should greatly reduce SARS-CoV-2 binding affinity. Other lemurs are predicted to be closer to catarrhines in their susceptibility. Our study suggests that apes and African and Asian monkeys, and some lemurs, are likely to be highly susceptible to SARS-CoV-2. Urgent actions have been undertaken to limit the exposure of great apes to humans, and similar efforts may be necessary for many other primate species., Amanda Melin et al. compare variation in 29 primate species at 12 amino acid residue sites coded by the ACE2 gene and show that apes and African and Asian monkeys exhibit the same set of twelve key amino acid residues as human ACE2. These results suggest that these primates are likely to be susceptible to SARS-CoV-2, whereas ACE2 gene sequences and protein-protein interaction models suggest reduced susceptibility for platyrrhines, tarsiers, lorisoids, and some lemurs.

Humans have a long evolutionary relationship with ethanol, pre-dating anthropogenic sources, and possess unusually efficient ethanol metabolism, through a mutation that evolved in our last common ancestor with African great apes. Increased exposure to dietary ethanol through fermenting fruits and nectars is hypothesized to have selected for this in our lineage. Yet, other mammals have frugivorous and nectarivorous diets, raising the possibility of natural ethanol exposure and adaptation in other taxa. We conduct a comparative genetic analysis of alcohol dehydrogenase class IV (ADH IV) across mammals to provide insight into their evolutionary history with ethanol. We find genetic variation and multiple pseudogenization events in ADH IV, indicating the ability to metabolize ethanol is variable. We suggest that ADH enzymes are evolutionarily plastic and show promise for revealing dietary adaptation. We further highlight the derived condition of humans and draw attention to problems with modelling the physiological responses of other mammals on them, a practice that has led to potentially erroneous conclusions about the likelihood of natural intoxication in wild animals. It is a fallacy to assume that other animals share our metabolic adaptations, rather than taking into consideration each species' unique physiology.

Bats are a diverse radiation of mammals of enduring interest for understanding the evolution of sensory specialization. Colour vision variation among species has previously been linked to roosting preferences and echolocation form in the suborder Yinpterochiroptera, yet questions remain about the roles of diet and habitat in shaping bat visual ecology. We sequenced OPN1SW and OPN1LW opsin genes for 20 species of leaf-nosed bats (family Phyllostomidae; suborder Yangochiroptera) with diverse roosting and dietary ecologies, along with one vespertilionid species (Myotis lavali). OPN1LW genes appear intact for all species, and predicted spectral tuning of long-wavelength opsins varied among lineages. OPN1SW genes appear intact and under purifying selection for Myotis lavali and most phyllostomid bats, with two exceptions: (a) We found evidence of ancient OPN1SW pseudogenization in the vampire bat lineage, and loss-of-function mutations in all three species of extant vampire bats; (b) we additionally found a recent, independently derived OPN1SW pseudogene in Lonchophylla mordax, a cave-roosting species. These mutations in leaf-nosed bats are independent of the OPN1SW pseudogenization events previously reported in Yinpterochiropterans. Therefore, the evolution of monochromacy (complete colour blindness) has occurred in both suborders of bats and under various evolutionary drivers; we find independent support for the hypothesis that obligate cave roosting drives colour vision loss. We additionally suggest that haematophagous dietary specialization and corresponding selection on nonvisual senses led to loss of colour vision through evolutionary sensory trade-off. Our results underscore the evolutionary plasticity of opsins among nocturnal mammals.

Copy number variation may be the most common form of structural genetic variation in the genome. Numerous studies have shown that gene copy number variation can correlate with phenotypic variation, where higher copy numbers correspond to increased expression of the protein and vice versa. Examples include some digestive enzyme genes, where variation in copy numbers and protein expression may be related to dietary differences. Increasing the expression of a digestive enzyme through higher gene copy numbers may thus be a potential mechanism for altering an organism’s digestive capabilities. I investigated copy number variation in genes coding for acidic mammalian chitinase, a chitinolytic digestive enzyme that may be used for the digestion of insect exoskeletons, in nonhuman primates with varying levels of insect consumption. I hypothesized that CHIA copy number correlates positively with level of insectivory, predicting higher copy numbers in more insectivorous primates. I assessed copy number variation with the QuantStudio 3D digital PCR platform, in a comparative sample of Old World and New World primate species (N = 10 species, one or two individuals each). Contrary to my prediction, no evidence of copy number variation was found and all species tested had two gene copies per diploid genome. These findings suggest that if acidic mammalian chitinase expression varies according to insect consumption in primates, it may be up- or downregulated through another mechanism.

Integrating evolutionary psychological and molecular genetic research may increase our knowledge of the psychological correlates of specific genes, as well as enhance evolutionary psychology's ability to explain individual differences. We tested the hypothesis that men's sexual jealousy mechanisms functionally calibrate their psychological output according to genetic variation at the androgen receptor locus. Mated men (N = 103) provided buccal cell samples for genotype fragment analysis and completed inventories assessing their sexually jealous cognitions and emotions. Results indicated that men with longer sequences of CAG codon repeats at the androgen receptor locus were more likely to perceive ambiguous social and environmental cues as indicative of their mates’ infidelity, and experienced greater emotional upset in response to these cues. These results contribute to a growing body of research linking polymorphism at the AR locus to individual differences in psychology, and, to our knowledge, provide the first evidence pointing toward the heritability of sexual jealousy. Our discussion centers on whether the heritability of psychological differences implies direct genetic influences on the neurobiological substrate, or reflects functionally calibrated output from sex-typical and species-typical mechanisms. We conclude by describing how future research can more clearly differentiate between these alternative genetic models.

In foregut-fermenting mammals (e.g., colobine monkeys, artiodactyl ruminants) the enzymes pancreatic ribonuclease (RNASE1) and lysozyme C (LYZ), originally involved in immune defense, have evolved new digestive functions. Howler monkeys are folivorous non-colobine primates that lack the multi-chambered stomachs of colobines and instead digest leaves using fermentation in the caeco-colic region. We present data on the RNASE1 and LYZ genes of four species of howler monkey (Alouatta spp.). We find that howler monkey LYZ is conserved and does not share the substitutions found in colobine and cow sequences, whereas RNASE1 was duplicated in the common ancestor of A. palliata, A. seniculus, A. sara, and A. pigra. While the parent gene (RNASE1) is conserved, the daughter gene (RNASE1B) has multiple amino acid substitutions that are parallel to those found in RNASE1B genes of colobines. The duplicated RNase in Alouatta has biochemical changes similar to those in colobines, suggesting a novel, possibly digestive function. These findings suggest that pancreatic ribonuclease has, in parallel, evolved a new role for digesting the products of microbial fermentation in both foregut- and hindgut-fermenting folivorous primates. This may be a vital digestive enzyme adaptation allowing howler monkeys to survive on leaves during periods of low fruit availability.

All living organisms need to consume nutrients to grow, survive, and reproduce, making the successful acquisition of food resources a powerful selective pressure. However, acquiring food is only part of the challenge. While all animals spend much of their daily activity budget hunting, searching for, or otherwise procuring food, a large part of what is involved in overall nutrition occurs once the meal has been swallowed. Most nutritional components are too complex for immediate use and must be broken down into simpler compounds, which can then be absorbed by the body. This process, digestion, is catalyzed by enzymes that are either endogenous or produced by the host's microbial population.1 Research shows that the nutritional value of food is partially constrained by the digestive abilities of the microbial community present in the host's gut and that these microbes rapidly adapt to changes in diet and other environmental pressures.2 An accumulating body of evidence suggests that endogenously produced digestive enzymes also have been, and still are, common targets of natural selection, further cementing their crucial role in an organism's digestive system.3-5.

Ecological flexibility, extended lifespans, and large brains, have long intrigued evolutionary biologists, and comparative genomics offers an efficient and effective tool for generating new insights into the evolution of such traits. Studies of capuchin monkeys are particularly well situated to shed light on the selective pressures and genetic underpinnings of local adaptation to diverse habitats, longevity, and brain development. Distributed widely across Central and South America, they are inventive and extractive foragers, known for their sensorimotor intelligence. Capuchins have the largest relative brain size of any monkey and a lifespan that exceeds 50 years, despite their small (3-5 kg) body size. We assemble ade novoreference genome forCebus imitatorand provide the first genome annotation of a capuchin monkey. Through high-depth sequencing of DNA derived from blood, various tissues and feces via fluorescence activated cell sorting (fecalFACS) to isolate monkey epithelial cells, we compared genomes of capuchin populations from tropical dry forests and lowland rainforests and identified population divergence in genes involved in water balance, kidney function, and metabolism. Through a comparative genomics approach spanning a wide diversity of mammals, we identified genes under positive selection associated with longevity and brain development. Additionally, we provide a technological advancement in the use of non-invasive genomics for studies of free-ranging mammals. Our intra- and interspecific comparative study of capuchin genomics provides new insights into processes underlying local adaptation to diverse and physiologically challenging environments, as well as the molecular basis of brain evolution and longevity.SIGNIFICANCESurviving challenging environments, living long lives, and engaging in complex cognitive processes are hallmark characteristics of human evolution. Similar traits have evolved in parallel in capuchin monkeys, but their genetic underpinnings remain unexplored. We developed and annotated a reference assembly for white-faced capuchin monkeys to explore the evolution of these phenotypes. By comparing populations of capuchins inhabiting rainforest versus dry forests with seasonal droughts, we detected selection in genes associated with kidney function, muscular wasting, and metabolism, suggesting adaptation to periodic resource scarcity. When comparing capuchins to other mammals, we identified evidence of selection in multiple genes implicated in longevity and brain development. Our research was facilitated by our new method to generate high- and low-coverage genomes from non-invasive biomaterials.

Insects are an important food resource for many primates, but the chitinous exoskeletons of arthropods have long been considered to be indigestible by the digestive enzymes of most mammals. However, recently mice and insectivorous bats were found to produce the enzyme acidic mammalian chitinase (AMCase) to digest insect exoskeletons. Here, we report on the gene CHIA and its paralogs, which encode AMCase, in a comparative sample of nonhuman primates. Our results show that early primates likely had three CHIA genes, suggesting that insects were an important component of the ancestral primate diet. With some exceptions, most extant primate species retain only one functional CHIA paralog. The exceptions include two colobine species, in which all CHIA genes have premature stop codons, and several New World monkey species that retain two functional genes. The most insectivorous species in our sample also have the largest number of functional CHIA genes. Tupaia chinensis and Otolemur garnettii retain three functional CHIA paralogs, whereas Tarsius syrichta has a total of five, two of which may be duplications specific to the tarsier lineage. Selection analyses indicate that CHIA genes are under more intense selection in species with higher insect consumption, as well as in smaller-bodied species (