Structurally divergent and recurrently mutated regions of primate genomes.

We sequenced and assembled using multiple long-read sequencing technologies the genomes of chimpanzee, bonobo, gorilla, orangutan, gibbon, macaque, owl monkey, and marmoset. We identified 1,338,997 lineage-specific fixed structural variants (SVs) disrupting 1,561 protein-coding genes and 136,932 regulatory elements, including the most complete set of human-specific fixed differences. We estimate that 819.47 Mbp or ∼27% of the genome has been affected by SVs across primate evolution. We identify 1,607 structurally divergent regions wherein recurrent structural variation contributes to creating SV hotspots where genes are recurrently lost (e.g., CARD, C4, and OLAH gene families) and additional lineage-specific genes are generated (e.g., CKAP2, VPS36, ACBD7, and NEK5 paralogs), becoming targets of rapid chromosomal diversification and positive selection (e.g., RGPD gene family). High-fidelity long-read sequencing has made these dynamic regions of the genome accessible for sequence-level analyses within and between primate species.

News and Perspectives: Words matter in primatology.

Postings on social media on Twitter (now X), BioAnthropology News (Facebook), and other venues, as well as recent publications in prominent journals, show that primatologists, ecologists, and other researchers are questioning the terms "Old World" and "New World" due to their colonial implications and history. The terms are offensive if they result in erasing Indigenous voices and history, ignoring the fact that Indigenous peoples were in the Americas long before European colonization. Language use is not without context, but alternative terminology is not always obvious and available. In this perspective, we share opinions expressed by an international group of primatologists who considered questions about the use of these terms, whether primatologists should adjust language use, and how to move forward. The diversity of opinions provides insight into how conventional terms used in primatological research and conservation may impact our effectiveness in these domains.

Identification of constrained sequence elements across 239 primate genomes.

Noncoding DNA is central to our understanding of human gene regulation and complex diseases1,2, and measuring the evolutionary sequence constraint can establish the functional relevance of putative regulatory elements in the human genome3-9. Identifying the genomic elements that have become constrained specifically in primates has been hampered by the faster evolution of noncoding DNA compared to protein-coding DNA10, the relatively short timescales separating primate species11, and the previously limited availability of whole-genome sequences12. Here we construct a whole-genome alignment of 239 species, representing nearly half of all extant species in the primate order. Using this resource, we identified human regulatory elements that are under selective constraint across primates and other mammals at a 5% false discovery rate. We detected 111,318 DNase I hypersensitivity sites and 267,410 transcription factor binding sites that are constrained specifically in primates but not across other placental mammals and validate their cis-regulatory effects on gene expression. These regulatory elements are enriched for human genetic variants that affect gene expression and complex traits and diseases. Our results highlight the important role of recent evolution in regulatory sequence elements differentiating primates, including humans, from other placental mammals.

Phylogenomic analyses provide insights into primate evolution.

Comparative analysis of primate genomes within a phylogenetic context is essential for understanding the evolution of human genetic architecture and primate diversity. We present such a study of 50 primate species spanning 38 genera and 14 families, including 27 genomes first reported here, with many from previously less well represented groups, the New World monkeys and the Strepsirrhini. Our analyses reveal heterogeneous rates of genomic rearrangement and gene evolution across primate lineages. Thousands of genes under positive selection in different lineages play roles in the nervous, skeletal, and digestive systems and may have contributed to primate innovations and adaptations. Our study reveals that many key genomic innovations occurred in the Simiiformes ancestral node and may have had an impact on the adaptive radiation of the Simiiformes and human evolution.

Mammalian evolution of human cis-regulatory elements and transcription factor binding sites.

Understanding the regulatory landscape of the human genome is a long-standing objective of modern biology. Using the reference-free alignment across 241 mammalian genomes produced by the Zoonomia Consortium, we charted evolutionary trajectories for 0.92 million human candidate cis-regulatory elements (cCREs) and 15.6 million human transcription factor binding sites (TFBSs). We identified 439,461 cCREs and 2,024,062 TFBSs under evolutionary constraint. Genes near constrained elements perform fundamental cellular processes, whereas genes near primate-specific elements are involved in environmental interaction, including odor perception and immune response. About 20% of TFBSs are transposable element-derived and exhibit intricate patterns of gains and losses during primate evolution whereas sequence variants associated with complex traits are enriched in constrained TFBSs. Our annotations illuminate the regulatory functions of the human genome.

Do zoo-housed primates retreat from crowds? A simple study of five primate species.

An animal's welfare state is directly influenced by the mental state, which is shaped by experiences within the environment throughout the animal's life. For zoo-housed animals, visitors to the zoo are a large part of that environment and a fluctuating influence within it. This study examines the impact of zoo visitors on the space use of five species of zoo-housed primates (Eastern black-and-white colobus monkeys, Colobus guereza, n = 5, Allen's swamp monkeys, Allenopithecus nigroviridis, n = 2, DeBrazza's monkeys, Cercopithecus neglectus, n = 3, Bolivian gray titi monkeys, Callicebus donacophilus, n = 3, and crowned lemurs, Eulemur coronatus, n = 3). Specifically, we considered whether primates' distance from visitor areas changed as crowd sizes increased. Data were collected using the ZooMonitor app. Observers recorded spatial coordinates for each animal over periods ranging from 12 to 32 months. Data were analyzed using two types of regression models (linear and logistic) to examine the influence of visitors on the location of the primates. Both analyses revealed a statistically significant but small decrease in primate distance from visitor viewing glass as the number of visitors increased. Behavioral indicators of welfare were also unaffected by the presence of visitors. These results suggest that, with additional validation, distance from visitors may be one promising, simple way to evaluate the influence of visitors on primate welfare.

Soil-transmitted helminth infections in free-ranging non-human primates from Cameroon and Gabon.

BACKGROUND: Zoonotic diseases are a serious threat to both public health and animal conservation. Most non-human primates (NHP) are facing the threat of forest loss and fragmentation and are increasingly living in closer spatial proximity to humans. Humans are infected with soil-transmitted helminths (STH) at a high prevalence, and bidirectional infection with NHP has been observed. The aim of this study was to determine the prevalence, genetic diversity, distribution and presence of co-infections of STH in free-ranging gorillas, chimpanzees and other NHP species, and to determine the potential role of these NHP as reservoir hosts contributing to the environmental sustenance of zoonotic nematode infections in forested areas of Cameroon and Gabon. METHODS: A total of 315 faecal samples from six species of NHPs were analysed. We performed PCR amplification, sequencing and maximum likelihood analysis of DNA fragments of the internal transcribed spacer 2 (ITS2) nuclear ribosomal DNA to detect the presence and determine the genetic diversity of Oesophagostomum spp., Necator spp. and Trichuris spp., and of targeted DNA fragments of the internal transcribed spacer 1 (ITS1) to detect the presence of Ascaris spp. RESULTS: Necator spp. infections were most common in gorillas (35 of 65 individuals), but also present in chimpanzees (100 of 222 individuals) and in one of four samples from greater spot-nosed monkeys. These clustered with previously described type II and III Necator spp. Gorillas were also the most infected NHP with Oesophagostomum (51/65 individuals), followed by chimpanzees (157/222 individuals), mandrills (8/12 samples) and mangabeys (7/12 samples), with O. stephanostomum being the most prevalent species. Oesophagostomum bifurcum was detected in chimpanzees and a red-capped mangabey, and a non-classified Oesophagostomum species was detected in a mandrill and a red-capped mangabey. In addition, Ternidens deminutus was detected in samples from one chimpanzee and three greater spot-nosed monkeys. A significant relative overabundance of co-infections with Necator and Oesophagostomum was observed in chimpanzees and gorillas. Trichuris sp. was detected at low prevalence in a gorilla, a chimpanzee and a greater spot-nosed monkey. No Ascaris was observed in any of the samples analysed. CONCLUSIONS: Our results on STH prevalence and genetic diversity in NHP from Cameroon and Gabon corroborate those obtained from other wild NHP populations in other African countries. Future research should focus on better identifying, at a molecular level, the species of Necator and Oesophagostomum infecting NHP and determining how human populations may be affected by increased proximity resulting from encroachment into sylvatic STH reservoir habitats.

L1 retrotransposons exploit RNA m6A modification as an evolutionary driving force.

L1 retrotransposons can pose a threat to genome integrity. The host has evolved to restrict L1 replication. However, mechanisms underlying L1 propagation out of the host surveillance remains unclear. Here, we propose an evolutionary survival strategy of L1, which exploits RNA m6A modification. We discover that m6A 'writer' METTL3 facilitates L1 retrotransposition, whereas m6A 'eraser' ALKBH5 suppresses it. The essential m6A cluster that is located on L1 5' UTR serves as a docking site for eukaryotic initiation factor 3 (eIF3), enhances translational efficiency and promotes the formation of L1 ribonucleoprotein. Furthermore, through the comparative analysis of human- and primate-specific L1 lineages, we find that the most functional m6A motif-containing L1s have been positively selected and became a distinctive feature of evolutionarily young L1s. Thus, our findings demonstrate that L1 retrotransposons hijack the RNA m6A modification system for their successful replication.

Interaction between matrix metalloproteinase-9 (MMP-9) and neutrophil gelatinase-associated lipocalin (NGAL): A recent evolutionary event in primates.

Matrix metalloproteases are known to represent an early step in the evolution of the immune system. Similarly, neutrophil gelatinase-associated lipocalin is known to be a key effector in immune response. MMP-9 interacts with NGAL, but their interaction mechanisms remain unclear. Functional interaction between proteins is ensured by coevolution. Protein coevolution was inferred by calculating the linear correlation coefficients between inter-protein distance matrices using MirrorTree. Among examined mammal species, we found a robust signal of MMP-9/NGAL coevolution exclusively within Primates (R = 0.96, p < 1e-06). Owing to the high conservation of these proteins among Mammals, we chose to utilize a recent version of Blocks in Sequences (BIS2) algorithm implemented in BIS2Analyzer webserver. Coevolution clusters between the two proteins were identified in MMP-9 fibronectin and hemopexin domains. Our results suggest that MMP-9/NGAL interaction is a recent evolutionary acquisition in Primates. Furthermore, MMP-9 hemopexin domain would represent a promising target for drug design against these molecules.

A robust alternative to assessing three-dimensional relative enamel thickness for the use in taxonomic assessment.

OBJECTIVE: Three-dimensional relative enamel thickness (3DRET) is important for assessing hypotheses about taxonomy, phylogeny, and dietary reconstruction for primates. However, its weaknesses have not been thoroughly investigated. Here, we analyze its weaknesses and propose an index aiming at better taxonomic discrimination. MATERIALS AND METHODS: The dimensionless 3D index, ratio of enamel-thickness to dentine-thickness (3DRED), which is defined as the cubic root of the ratio of 3D average enamel thickness (3DAET) to 3D average dentine thickness (3DADT), is proposed here. To compare 3DRET and 3DRED and their sensitivity to voxel size, a fossil orangutan molar was scanned 14 times with different resolutions ranging from 10 to 50 µm. Enamel thickness analysis was carried out for each resultant digital model. In addition, enamel thickness measurements of 179 mandibular permanent molars (eight genera) were analyzed, followed by investigating the relationship between 3DRET and 3DAET and between 3DRED and 3DAET. RESULTS: Regarding sensitivity, 3DRED is more robust than 3DRET. In addition, 3DRET is correlated with 3DAET by linear curve with regression coefficients approximating or larger than 0.8 in most cases, while 3DRED shows less correlation with 3DAET. Furthermore, there are clear separations between different taxa in the bivariate plot of 3DRED against 3DAET, indicative of the taxonomic value of 3DRED. CONCLUSION: Under certain conditions, 3DRED promises to be a robust and reliable alternative to 3DRET in taxonomic study.

Total evidence or taxonomic congruence? A comparison of methods for combining biological evidence.

Phylogenetic inference proposes an evolutionary hypothesis for a group of taxa which is usually represented as a phylogenetic tree. The use of several distinct biological evidence has shown to produce more resolved phylogenies than single evidence approaches. Currently, two conflicting paradigms are applied to combine biological evidence: taxonomic congruence (TC) and total evidence (TE). Although the literature recommends the application of these paradigms depending on the congruence of the input data, the resultant evolutionary hypotheses could vary according to the strategy used to combine the biological evidence biasing the resultant topologies of the trees. In this work, we evaluate the ability of different strategies associated with both paradigms to produce integrated evolutionary hypotheses by considering different features of the data: missing biological evidence, diversity among sequences, complexity, and congruence. Using datasets from the literature, we compare the resultant trees with reference hypotheses obtained by applying two inference criteria: maximum parsimony and likelihood. The results show that methods associated with TE paradigm are more robust compared to TC methods, obtaining trees with more similar topologies in relation to reference trees. These results are obtained regardless of (1) the features of the data, (2) the estimated evolutionary rates, and (3) the criteria used to infer the reference evolutionary hypotheses.

Evolution of HLA-F and its orthologues in primate species: a complex tale of conservation, diversification and inactivation.

HLA-F represents one of the nonclassical MHC class I molecules in humans. Its main characteristics involve low levels of polymorphism in combination with a restricted tissue distribution. This signals that the gene product executes a specialised function, which, however, is still poorly understood. Relatively little is known about the evolutionary equivalents of this gene in nonhuman primates, especially with regard to population data. Here we report a comparative genetic analysis of the orthologous genes of HLA-F in various great ape, Old World monkey (OWM), and New World monkey (NWM) species. HLA-F-related transcripts were found in all subjects studied. Low levels of polymorphism were encountered, although the length of the predicted gene products may vary. In most species, one or two transcripts were discovered, indicating the presence of only one active F-like gene per chromosome. An exception was provided by a New World monkey species, namely, the common marmoset. In this species, the gene has been subject to duplication, giving rise to up to six F-like transcripts per animal. In humans, great apes, and OWM, and probably the majority of the NWM species, the evolutionary equivalents of the HLA-F gene experienced purifying selection. In the marmoset, however, the gene was initially duplicated, but the expansion was subjected afterwards to various mechanisms of genetic inactivation, as evidenced by the presence of pseudogenes and an array of genetic artefacts in a section of the transcripts.

Daily Distance Traveled Is Associated with Greater Brain Size in Primates.

Explanations for the brain size increments through primate and, particularly, human evolution are numerous. Commonly, these hypotheses rely on the influence that behavioral and ecological variables have on brain size in extant primates, such as diet quality, social group size, or home range (HR) area. However, HR area does not reflect the time spent moving. As such, it has not been properly addressed whether the effort involved in movement could have affected brain size evolution in primates. This study aimed to test the influence of daily movement on primates' brain sizes, controlling for these other behavioral and ecological factors. We used a large comparative dataset of extant primate species and phylogenetic comparative methods. Our results show a significant correlation between daily movement and brain mass, which is not explained by the influence of diet, social group size, HR, or body mass. Hence, from an evolutionary timescale, a longer daily movement distance is not a constraining factor for the energetic investment in a larger brain. On the contrary, increased mobility could have contributed to brain mass incrementations through evolution.

Rapid evolution of the primate larynx?

Tissue vibrations in the larynx produce most sounds that comprise vocal communication in mammals. Larynx morphology is thus predicted to be a key target for selection, particularly in species with highly developed vocal communication systems. Here, we present a novel database of digitally modeled scanned larynges from 55 different mammalian species, representing a wide range of body sizes in the primate and carnivoran orders. Using phylogenetic comparative methods, we demonstrate that the primate larynx has evolved more rapidly than the carnivoran larynx, resulting in a pattern of larger size and increased deviation from expected allometry with body size. These results imply fundamental differences between primates and carnivorans in the balance of selective forces that constrain larynx size and highlight an evolutionary flexibility in primates that may help explain why we have developed complex and diverse uses of the vocal organ for communication.

Evolution of the mutation rate across primates.

Germline mutations are the source of all heritable variation. In the past few years, whole genome sequencing has allowed direct and comprehensive surveys of mutation patterns in humans and other species. These studies have documented substantial variation in both mutation rates and spectra across primates, the causes of which remain unclear. Here, we review what is currently known about mutation rates in primates, highlight the factors proposed to explain the variation across species, and discuss some implications of these findings on our understanding of the chronology of primate evolution and the process of mutagenesis.

Abundance, Diversity, and Distribution of Primates at Welel Mountain, Kellem Wollega Zone, Oromia Region, Ethiopia.

Primates are the mammals of the order Primate that is characterized by advanced development of binocular vision and enlargement of the cerebral hemispheres. The aim of this study was to investigate the abundance, diversity, and distribution of primates on Welel Mountain. From August 2017 to February 2018, we collected data from different parts of Welel Mountain during wet and dry seasons of the year and analyzed them using SPSS version 20. We identified four primate species: Chlorocebus aethiops, Cercopithecus mitis, Papio anubis, and Colobus guereza. We conducted t-test analysis for abundance and distribution of primates in wet and dry season of the year, and the P value obtained was 0.20. The mean percentages of primates in forest, woodland, and shrubs were 43.16%, 32.26%, and 24.58%, respectively. Shannon-Wiener diversity index (H') value was higher in wet season than in dry season. The current study showed that the species are distributed more evenly in wet season than in dry season, and the number of young individuals is more than that of adults. This indicates that currently the status of primates population on Welel Mountain is good. Therefore, to keep the status of primates in the study area effective, wildlife management and conservation policy should be formulated.

Relaxed constraint and functional divergence of the progesterone receptor (PGR) in the human stem-lineage.

The steroid hormone progesterone, acting through the progesterone receptor (PR), a ligand-activated DNA-binding transcription factor, plays an essential role in regulating nearly every aspect of female reproductive biology. While many reproductive traits regulated by PR are conserved in mammals, Catarrhine primates evolved several derived traits including spontaneous decidualization, menstruation, and a divergent (and unknown) parturition signal, suggesting that PR may also have evolved divergent functions in Catarrhines. There is conflicting evidence, however, whether the progesterone receptor gene (PGR) was positively selected in the human lineage. Here we show that PGR evolved rapidly in the human stem-lineage (as well as other Catarrhine primates), which likely reflects an episode of relaxed selection intensity rather than positive selection. Coincident with the episode of relaxed selection intensity, ancestral sequence resurrection and functional tests indicate that the major human PR isoforms (PR-A and PR-B) evolved divergent functions in the human stem-lineage. These results suggest that the regulation of progesterone signaling by PR-A and PR-B may also have diverged in the human lineage and that non-human animal models of progesterone signaling may not faithfully recapitulate human biology.

Broad-scale morpho-functional traits of the mandible suggest no hard food adaptation in the hominin lineage.

An on-going debate concerning the dietary adaptations of archaic hominins and early Homo has been fuelled by contradictory inferences obtained using different methodologies. This work presents an extensive comparative sample of 30 extant primate species that was assembled to perform a morpho-functional comparison of these taxa with 12 models corresponding to eight fossil hominin species. Finite Element Analysis and Geometric Morphometrics were employed to analyse chewing biomechanics and mandible morphology to, firstly, establish the variation of this clade, secondly, relate stress and shape variables, and finally, to classify fossil individuals into broad ingesta related hardness categories using a support vector machine algorithm. Our results suggest that some hominins previously assigned as hard food consumers (e.g. the members of the Paranthropus clade) in fact seem to rely more strongly on soft foods, which is consistent with most recent studies using either microwear or stable isotope analyses. By analysing morphometric and stress results in the context of the comparative framework, we conclude that in the hominin clade there were probably no hard-food specialists. Nonetheless, the biomechanical ability to comminute harder items, if required as fallback option, adds to their strategy of increased flexibility.

Effect of river size on Amazonian primate community structure: A biogeographic analysis using updated taxonomic assessments.

The mechanisms that underlie the diversification of Neotropical primates remain contested. One mechanism that has found support is the riverine barrier hypothesis (RBH), which postulates that large rivers impede gene flow between populations on opposite riverbanks and promote allopatric speciation. Ayres and Clutton-Brock (1992) demonstrated that larger Amazonian rivers acted as barriers, delineating the distribution limits of primate species. However, profound changes in taxonomy and species concepts have led to the proliferation of Neotropical primate taxa, which may have reduced support for their results. Using the most recent taxonomic assessments and distribution maps, we tested the effect of increasing river size on the similarity of opposite riverbank primate communities in the Amazon. First, we conducted a literature review of primate taxonomy and developed a comprehensive spatial database, then applied geographical information system to query mapped primate ranges against the riverine geography of the Amazon watershed to produce a similarity index for opposite riverbank communities. Finally, we ran models to test how measures of river size predicted levels of similarity. We found that, almost without exception, similarity scores were lower than scores from Ayres and Clutton-Brock (1992) for the same rivers. Our model showed a significant negative relationship between streamflow and similarity in all tests, and found river width significant for the segmented Amazon, but not for multiple Amazon watershed rivers. Our results support the RBH insofar as they provide evidence for the prediction that rivers with higher streamflow act as more substantial barriers to dispersal, and accordingly exhibit greater variation in community composition between riverbanks.

The evolution of the vestibular apparatus in apes and humans.

Phylogenetic relationships among extinct hominoids (apes and humans) are controversial due to pervasive homoplasy and the incompleteness of the fossil record. The bony labyrinth might contribute to this debate, as it displays strong phylogenetic signal among other mammals. However, the potential of the vestibular apparatus for phylogenetic reconstruction among fossil apes remains understudied. Here we test and quantify the phylogenetic signal embedded in the vestibular morphology of extant anthropoids (monkeys, apes and humans) and two extinct apes (Oreopithecus and Australopithecus) as captured by a deformation-based 3D geometric morphometric analysis. We also reconstruct the ancestral morphology of various hominoid clades based on phylogenetically-informed maximum likelihood methods. Besides revealing strong phylogenetic signal in the vestibule and enabling the proposal of potential synapomorphies for various hominoid clades, our results confirm the relevance of vestibular morphology for addressing the controversial phylogenetic relationships of fossil apes.

Humans, gorillas, chimpanzees, orangutans and gibbons all belong to a group known as the hominoids. This 'superfamily' also includes the immediate ancestors and close relatives of these species, however in many instances the evolutionary relationships between these extinct ape species remain controversial. While DNA can help evolutionary biologists to work out how living species are related to one another, fossils are typically the principle source of information for extinct species. Inferring evolutionary relationships from fossils must be done with caution, but the bony cavity that houses the inner ear ­ which is involved in balance and hearing and fairly common in the fossil record ­ has proven useful for tracing the evolution of certain groups of mammals. However, no one had previously looked to see if this structure could give insights into the evolutionary relatedness among living and extinct hominoids. Urciuoli et al. have now used a 3D imaging technique to capture the complex shapes of the inner ear cavities of 27 species of monkeys and apes, including humans and two extinct apes (Oreopithecus and Australopithecus). The results confirmed that the shape of these structures most closely reflected the evolutionary relationships between the species and not, for example, how the animals moved. Urciuoli et al. went on to identify features of these bony chambers that were shared within several hominoid groups, and to estimate what the inner ears of the ancestors of these groups might have looked like. The results for Australopithecus, for example, were consistent with it being most closely related to modern humans than other apes, while those for the enigmatic Oreopithecus supported the view that it was a much older species of ape that converged in some respects with other apes still alive today. The findings highlight the potential of the inner ear for reconstructing the early branches of our family tree. They also offer the prospect of refining the controversial evolutionary relationships within the impressive diversity of extinct ape species.