Primate Evolution Research Articles

A transposable element prevents severe hemophilia B and provides insights into the evolution of new- and old world primates.

Alu-elements comprise a large part of the human genome and some insertions have been shown to cause diseases. Here, we illuminate the protective role of an Alu-element in the 3'UTR of the human Factor 9 gene and its ability to ameliorate a poly(A) site mutation in a hemophilia B patient, preventing him from developing a severe disease. Using a minigene, we examined the disease-causing mutation and the modifying effect of the transposon in cellulo. Further, we simulated evolutionary scenarios regarding alternative polyadenylation before and after Alu insertion. A sequence analysis revealed that Old World monkeys displayed a highly conserved polyadenylation sites in this Alu-element, whereas New World monkeys lacked this motif, indicating a selective pressure. We conclude that this transposon has inserted shortly before the separation of Old and New World monkeys and thus also serves as a molecular landmark in primate evolution.

Sexual Dimorphism and Divergent Evolutionary Pathways in Primate Cranial Biomechanics: Insights From a Theoretical Morphology Framework.

The mammalian order Primates is known for widespread sexual dimorphism in size and phenotype. Despite repeated speculation that primate sexual size dimorphism either facilitates or is in part driven by functional differences in how males and females interact with their environments, few studies have directly assessed the influence of sexual dimorphism on performance traits. Here, we use a theoretical morphology framework to show that sexual dimorphism in primate crania is associated with divergent biomechanical performance traits. The degree of dimorphism is a significant covariate in biomechanical trait divergence between sexes. Males exhibit less efficient but stiffer cranial shapes and significant evolutionary allometry in biomechanical performance, whereas females maintain performance stability across their size spectrum. Evolutionary rates are elevated for efficiency in females whereas males emphasize size-dependent cranial stiffness. These findings support a hypothesis of sex-linked bifurcation in masticatory system performance: larger male crania and faster size evolution partially compensate for low efficiency and reflect a de-emphasis of mechanical leverage, whereas female crania maintain higher mechanical efficiency overall and evolve more rapidly in molar-based masticatory performance. The evolutionary checks-and-balances between size dimorphism and cranial mechanical performance may be a more important driver of primate phenotypic evolution than has been hitherto appreciated.

A coati conundrum: how variation in levels of arboreality influences gait mechanics among three musteloid species.

The gait characteristics associated with arboreal locomotion have been frequently discussed in the context of primate evolution, wherein they present as a trio of distinctive features: a diagonal-sequence, diagonal-couplet gait pattern; a protracted arm at forelimb touchdown; and a hindlimb-biased weight support pattern. The same locomotor characteristics have been found in the woolly opossum, a fine-branch arborealist similar in ecology to some small-bodied primates. To further our understanding of the functional link between arboreality and primate-like locomotion, we present comparative data collected in the laboratory for three musteloid taxa. Musteloidea represents an ecologically diverse superfamily spanning numerous locomotor specializations that includes the highly arboreal kinkajou (Potos flavus), mixed arboreal/terrestrial red pandas (Ailurus fulgens) and primarily terrestrial coatis (Nasua narica). This study applies a combined kinetic and kinematic approach to compare the locomotor behaviors of these three musteloid taxa, representing varying degrees of arboreal specialization. We observed highly arboreal kinkajous to share many locomotor traits with primates. In contrast, red pandas (mixed terrestrial/arborealist) showed gait characteristics found in most non-primate mammals. Coatis, however, demonstrated a unique combination of locomotor traits, combining a lateral-sequence, lateral-couplet gait pattern typical of long-legged, highly terrestrial mammals, varying degrees of arm protraction, and a hindlimb-biased weight support pattern typical of most primates and woolly opossums. We conclude that the three gait characteristics traditionally used to describe arboreal walking in primates can occur independently from one another and not necessarily as a suite of interdependent characteristics, a phenomenon that has been reported for some primates.

Evolution of translational control and the emergence of genes and open reading frames in human and non-human primate hearts.

Evolutionary innovations can be driven by changes in the rates of RNA translation and the emergence of new genes and small open reading frames (sORFs). In this study, we characterized the transcriptional and translational landscape of the hearts of four primate and two rodent species through integrative ribosome and transcriptomic profiling, including adult left ventricle tissues and induced pluripotent stem cell-derived cardiomyocyte cell cultures. We show here that the translational efficiencies of subunits of the mitochondrial oxidative phosphorylation chain complexes IV and V evolved rapidly across mammalian evolution. Moreover, we discovered hundreds of species-specific and lineage-specific genomic innovations that emerged during primate evolution in the heart, including 551 genes, 504 sORFs and 76 evolutionarily conserved genes displaying human-specific cardiac-enriched expression. Overall, our work describes the evolutionary processes and mechanisms that have shaped cardiac transcription and translation in recent primate evolution and sheds light on how these can contribute to cardiac development and disease.

Technical note: A biological anthropologist's guide for applying microbiome science to studies of human and non-human primates.

A central goal of biological anthropology is connecting environmental variation to differences in host physiology, biology, health, and evolution. The microbiome represents a valuable pathway for studying how variation in host environments impacts health outcomes. While there are many resources for learning about methods related to microbiome sample collection, laboratory analyses, and genetic sequencing, there are fewer dedicated to helping researchers navigate the dense portfolio of bioinformatics and statistical approaches for analyzing microbiome data. Those that do exist are rarely related to questions in biological anthropology and instead are often focused on human biomedicine. To address this gap, we expand on existing tutorials and provide a "road map" to aid biological anthropologists in understanding, selecting, and deploying the data analysis and visualization methods that are most appropriate for their specific research questions. Leveraging an existing dataset of fecal samples and survey data collected from wild geladas living in Simien Mountains National Park in Ethiopia (Baniel et al., 2021), this paper guides researchers toward answering three questions related to variation in the gut microbiome across host and environmental factors. By providing explanations, examples, and a reproducible workflow for different analytic methods, we move beyond the theoretical benefits of considering the microbiome within anthropological research and instead present researchers with a guide for applying microbiome science to their work. This paper makes microbiome science more accessible to biological anthropologists and paves the way for continued research into the microbiome's role in the ecology, evolution, and health of human and non-human primates.

Commemorating the monkey bars, catalyst of debate at the intersection of human evolutionary biology and public health.

Play is an essential part of childhood, and growing attention has focused on the potential health benefits of 'risky' or 'thrill-seeking' play. Such play behavior is readily observed on any playground, where it can sometimes lead to injuries--most often from fall impacts--that require medical attention. Monkey bars account for ~7% of childhood arm fractures in the USA, an alarming statistic that raises difficult questions over its costs and benefits. Many authors view monkey bars as a public health hazard, but it is plausible that our childhood impulse toward thrill-seeking play is a result of selective pressures throughout our primate evolutionary history. Indeed, emerging evidence suggests that the developmental benefits of thrill-seeking play extend into adulthood, outweighing the occasional costs of injury. Disparate and consequential, these dueling perspectives have fueled debate among health professionals and policymakers, but with little attention to the work of biological anthropologists. Here we call attention to the hominin fossil record and play behaviors of non-human primates, providing a novel perspective that bolsters arguments for the adaptive significance of thrill-seeking play. The moment for such a review is timely, for it commemorates the centennial anniversaries of two playground icons: the jungle gym and monkey bars.

The primate-specific presence of interferon regulatory factor-5 pseudogene 1.

Interferon regulatory factor 5 (IRF5) is a key transcription factor in inflammatory and immune responses, with its dysregulation linked to autoimmune diseases. Using bioinformatic approaches, including Basic Local Alignment Search Tool (BLAST) for sequence similarity searches, BLAST-Like Alignment Tool (BLAT) for genome-wide alignments, and several phylogenetics software, such as Multiple Alignment using Fast Fourier Transform (MAFFT), for phylogenetic analyses, we characterized the structure, origin, and evolutionary history of the human IRF5 pseudogene 1 (IRF5P1). Our analyses reveal that IRF5P1 is a chimeric processed pseudogene containing sequences derived from multiple sources, including IRF5-like sequences from disparate organisms. We find that IRF5P1 is specific to higher primates, likely originating through an ancient retroviral integration event approximately 60 million years ago. Interestingly, IRF5P1 resides within the triple QxxK/R motif-containing (TRIQK) gene, and its antisense strand is predominantly expressed as part of the TRIQK pre-messenger RNA (mRNA). Analysis of publicly available RNA-seq data suggests potential expression of antisense IRF5P1 RNA. We hypothesize that this antisense RNA may regulate IRF5 expression through complementary binding to IRF5 mRNA, with human genetic variants potentially modulating this interaction. The conservation of IRF5P1 in the primate lineage suggests its positive effects on primate evolution and innate immunity. This study highlights the importance of investigating pseudogenes and their potential regulatory roles in shaping lineage-specific immune adaptations.

Epigenetic regulation of HERVs: Implications for cancer immunotherapy.

Human endogenous retroviruses (HERVs), integrated into the human genome during primate evolution, constitute approximately 8% of the human genome. Although most HERVs are non-protein-coding owing to mutations, insertions, deletions, and truncations, recent research has revealed their diverse roles in biological processes, including disease pathogenesis. Although many HERVs remain inactive, they have been implicated in various diseases, particularly cancer, prompting an increased interest in harnessing HERVs for therapeutic purposes. This review explores the recent advancements in our understanding of the biological roles of HERVs, emphasizing their clinical relevance in cancer treatment. Here, we discuss how the detection of transposable elements (TEs), including HERVs, by the immune system triggers innate immune responses in human cancers. Additionally, we outline recent progress in elucidating the implications of HERV activation in cancer and how targeting HERVs holds promise for anti-cancer treatments by modulating epigenetic plasticity and disrupting cancer initiation and progression.

Hippocampal connectivity patterns echo macroscale cortical evolution in the primate brain

While the hippocampus is key for human cognitive abilities, it is also a phylogenetically old cortex and paradoxically considered evolutionarily preserved. Here, we introduce a comparative framework to quantify preservation and reconfiguration of hippocampal organisation in primate evolution, by analysing the hippocampus as an unfolded cortical surface that is geometrically matched across species. Our findings revealed an overall conservation of hippocampal macro- and micro-structure, which shows anterior-posterior and, perpendicularly, subfield-related organisational axes in both humans and macaques. However, while functional organisation in both species followed an anterior-posterior axis, we observed a marked reconfiguration in the latter across species, which mirrors a rudimentary integration of the default-mode-network in non-human primates. Here we show that microstructurally preserved regions like the hippocampus may still undergo functional reconfiguration in primate evolution, due to their embedding within heteromodal association networks.

The origin and evolution of primates

The origin and evolution of primates

Ecological and genetic variables co-vary with social group identity to shape the gut microbiome of a pair-living primate.

Primates exhibit diverse social systems that are intricately linked to their biology, behavior, and evolution, all of which influence the acquisition and maintenance of their gut microbiomes (GMs). However, most studies of wild primate populations focus on taxa with relatively large group sizes, and few consider pair-living species. To address this gap, we investigate how a primate's social system interacts with key environmental, social, and genetic variables to shape the GMin pair-living, red-bellied lemurs (Eulemur rubriventer). Previous research on this species suggests that social interactions within groups influence interindividual microbiome similarity; however, the impacts of other nonsocial variables and their relative contributions to gut microbial variation remain unclear. We sequenced the 16S ribosomal RNA hypervariable V4-V5 region to characterize the GM from 26 genotyped individuals across 11social groups residing in Ranomafana National Park, Madagascar. We estimated the degree to which sex, social group identity, genetic relatedness, dietary diversity, and home range proximity were associated with variation in the gut microbial communities residing in red-bellied lemurs. All variables except sex played a significant role in predicting GM composition. Our model had high levels of variance inflation, inhibiting our ability to determine which variables were most predictive of gut microbial composition. This inflation is likely due to red-bellied lemurs' pair-living, pair-bonded social system that leads to covariation among environmental, social, and genetic variables. Our findings highlight some of the factors that predict GMcomposition in a tightly bonded, pair-living species and identify variables that require further study. We propose that future primate microbiome studies should simultaneously consider environmental, social, and genetic factors to improve our understanding of the relationships among sociality, the microbiome, and primate ecology and evolution.

Comprehensive Identification and Characterization of HML-9 Group in Chimpanzee Genome.

Endogenous retroviruses (ERVs) are related to long terminal repeat (LTR) retrotransposons, comprising gene sequences of exogenous retroviruses integrated into the host genome and inherited according to Mendelian law. They are considered to have contributed greatly to the evolution of host genome structure and function. We previously characterized HERV-K HML-9 in the human genome. However, the biological function of this type of element in the genome of the chimpanzee, which is the closest living relative of humans, largely remains elusive. Therefore, the current study aims to characterize HML-9 in the chimpanzee genome and to compare the results with those in the human genome. Firstly, we report the distribution and genetic structural characterization of the 26 proviral elements and 38 solo LTR elements of HML-9 in the chimpanzee genome. The results showed that the distribution of these elements displayed a non-random integration pattern, and only six elements maintained a relatively complete structure. Then, we analyze their phylogeny and reveal that the identified elements all cluster together with HML-9 references and with those identified in the human genome. The HML-9 integration time was estimated based on the 2-LTR approach, and the results showed that HML-9 elements were integrated into the chimpanzee genome between 14 and 36 million years ago and into the human genome between 18 and 49 mya. In addition, conserved motifs, cis-regulatory regions, and enriched PBS sequence features in the chimpanzee genome were predicted based on bioinformatics. The results show that pathways significantly enriched for ERV LTR-regulated genes found in the chimpanzee genome are closely associated with disease development, including neurological and neurodevelopmental psychiatric disorders. In summary, the identification, characterization, and genomics of HML-9 presented here not only contribute to our understanding of the role of ERVs in primate evolution but also to our understanding of their biofunctional significance.

Multidimensional primate niche space sheds light on interspecific competition in primate evolution

Characterising how the totality of primate diversity is distributed across the order, and how it evolved, is challenging because diversity in individual traits often show opposing phylogenetic patterns. A species’ combination of traits can be conceptualised as its ‘niche’. Here, we describe and analyse seven-dimensional niche space, comprising 11 traits, for 191 primate species. Multifaceted diversity is distributed unequally among taxonomic groups. Cercopithecoidea and Hominidae occupy the largest areas of niche space, and are the most diverse families; platyrrhine families occupy small areas, and this space overlaps with strepsirrhines. The evolution of species’ locations in niche space is regulated by selection for adaptive optima in trait combinations. Given that niche similarity results in interspecific competition, we quantify two measures of species’ niche locations relative to others. We find that omnivores, frugivores, and species tolerating higher temperatures experience stronger interspecific competition. Hominidae occupation of niche space suggests competitive exclusion from niches by Cercopithecoidea over evolutionary time; but living great apes experience the lowest levels of interspecific competition. Callitrichids experience the highest levels of interspecific competition. Our results provide a standardised measure of primate niches that sheds light on the partitioning and evolution of primate diversity, and how this is driven by interspecific competition.

New records of early Paleocene (earliest Torrejonian) plesiadapiforms from northeastern Montana, USA, provide a window into the diversification of stem primates

Plesiadapiforms (putative stem primates) appear in the fossil record shortly after the Cretaceous/Paleogene boundary and subsequently radiated throughout the Paleocene into a taxonomically and ecomorphologically diverse group. The oldest known plesiadapiforms come from early Puercan (the oldest North American Land Mammal ‘age’ [NALMA] of the Cenozoic) deposits in northeastern Montana, and all records of Puercan plesiadapiforms are taxonomically restricted to members of the Purgatoriidae and the enigmatic genus Pandemonium. Plesiadapiform diversity substantially increased in the following Torrejonian NALMA, but the sparse record of faunas between the Puercan and the well-known middle and late Torrejonian has hampered our understanding of this important interval in early primate evolution. Here we report new plesiadapiform dental fossils from early Torrejonian (To1) deposits from the Tullock Member of the Fort Union Formation in northeastern Montana that record several poorly known taxa including members of the Purgatoriidae, Paromomyidae and Pandemonium, and that document the largest and most diverse assemblage of To1 plesiadapiforms known. We describe a new species of the purgatoriid Ursolestes (Ursolestes blissorum, sp. nov.) that represents the largest plesiadapiform known from the early Paleocene and, among other taxa, provides additional evidence that the temporal range of purgatoriids extended into the Torrejonian. Large sample sizes of the oldest known paromomyid, Paromomys farrandi, allowed us to document intraspecific variability and one undescribed tooth locus. Our observations illuminate changes in dental morphology of some taxa that occurred in To1 and may inform the acquisition of certain diagnostic plesiadapiform dental characters. We evaluate plesiadapiform species richness, mean body mass and body-mass disparity through the Paleocene and reveal unrecognized levels of richness in To1 and a general trend of stable body mass and body-mass disparity. Our findings contribute to documented patterns of plesiadapiform provincialism in the early Paleocene and shed light on the early stages of their Torrejonian radiation.

Terrestriality across the primate order: A review and analysis of ground use in primates.

Terrestriality is relatively rare in the predominantly arboreal primate order. How frequently, and when, terrestriality appears in primate evolution, and the factors that influence this behavior, are not well understood. To investigate this, we compiled data describing terrestriality in 515 extant nonhuman primate taxa. We describe the geographic and phylogenetic distribution of terrestriality, including an ancestral state reconstruction estimating the frequency and timing of evolutionary transitions to terrestriality. We review hypotheses concerning the evolution of primate terrestriality and test these using data we collected pertaining to characteristics including body mass and diet, and ecological factors including forest structure, food availability, weather, and predation pressure. Using Bayesian analyses, we find body mass and normalized difference vegetation index are the most reliable predictors of terrestriality. When considering subsets of taxa, we find ecological factors such as forest height and rainfall, and not body mass, are the most reliable predictors of terrestriality for platyrrhines and lemurs.

An unusual configuration of two anomalies in the extensor digitorum profundus complex in a human.

The extensor digitorum profundus complex underwent degeneration of the ulnar segments during primate adaptation and evolution. This process resulted in the preservation of only the extensor pollicis longus and extensor indicis in some apes, including humans. Consequently, anatomical variations within the digitorum profundus complex in modern humans have been well-documented, with detailed reports on their frequency and patterns in previous studies. Here, we report an unusual arrangement involving two anomalies in the extensor digitorum profundus complex, identified in a 66-year-old Japanese male cadaver. In this cadaver, two accessory muscles differentiated from both the extensor pollicis longus and extensor indicis. Notably, the latter muscle featured a tendon bifurcating towards both the thumb and index fingers, referred to as the extensor pollicis et indicis communis. Under the extensor retinaculum, the tendon of the accessory extensor pollicis longus passed through an independent compartment, whereas that of the extensor pollicis et indicis communis traversed a compartment shared by the extensor indicis and the extensor digitorum communis. Both muscles were innervated by the posterior interosseous nerve. Previous studies have reported that the accessory slip of the extensor pollicis longus and extensor pollicis et indicis communis appear at frequencies of 0.6% and 0.4-1.4%, respectively. However, to the best of our knowledge, a configuration in which both appear simultaneously has not been reported. The data from this case could provide essential insights into the variations in the extensor digitorum profundus complex in humans and non-human primates.

Relationships between Bitter Taste Receptor Gene Evolution, Diet, and Gene Repertoire in Primates.

Bitter taste perception plays a critical role in deterring animals from consuming harmful and toxic substances. To characterize the evolution of primate Tas2r, test the generality of Tas2r duplication in Cercopithecidae species, and examine whether dietary preferences have shaped the Tas2r repertoire of primate species, we identified Tas2r in the genomes of 35 primate species, including 16 Cercopithecidae, 6 Hominidae, 4 Cebidae, 3 Lemuridae, and 6 other species. The results showed that the total number of primate Tas2r ranged from 27 to 51, concentrating on 2 to 4 scaffolds of each species. Closely related genes were tandemly duplicated in the same scaffold. Phylogenetic construction revealed that Tas2r can be divided into 21 clades, including anthropoid-, Strepsirrhini-, and Cercopithecidae-specific Tas2r duplications. Phylogenetically independent contrast analysis revealed that the number of intact Tas2r significantly correlated with feeding preferences. Altogether, our data support diet as a driver of primate Tas2r evolution, and Cercopithecidae species have developed some specific Tas2r duplication during evolution. These results are probably because most Cercopithecidae species feed on plants containing many toxins, and it is necessary to develop specialized Tas2r to protect them from poisoning.

Conservation of a Chromosome 8 Inversion and Exon Mutations Confirm Common Gulonolactone Oxidase Gene Evolution Among Primates, Including H. Neanderthalensis

Ascorbic acid functions as an antioxidant and facilitates other biochemical processes such as collagen triple helix formation, and iron uptake by cells. Animals which endogenously produce ascorbic acid have a functional gulonolactone oxidase gene (GULO); however, humans have a GULO pseudogene (GULOP) and depend on dietary ascorbic acid. In this study, the conservation of GULOP sequences in the primate haplorhini suborder were investigated and compared to the GULO sequences belonging to the primates strepsirrhini suborder. Phylogenetic analysis suggested that the conserved GULOP exons in the haplorhini primates experienced a high rate of mutations following the haplorhini/strepsirrhini divergence. This high mutation rate has decreased during the evolution of the haplorhini primates. Additionally, indels of the haplorhini GULOP sequences were conserved across the suborder. A separate analysis for GULO sequences and well-conserved GULOP sequences focusing on placental mammals identified an in-frame GULO sequence in the Brazilian guinea pig, and a potential GULOP sequence in the pika. Similar to haplorhini primates, the guinea pig and lagomorph species have experienced a high substitution rate when compared to the mammals used in this study. A shared synteny to examine the conservation of local genes near GULO/GULOP identified a conserved inversion around the GULO/GULOP locus between the haplorhini and strepsirrhini primates. Fischer’s exact test did not support an association between GULOP and the chromosomal inversion. Mauve alignment showed that the inversion of the length of the syntenic block that the GULO/GULOP genes belonged to was variable. However, there were frequent rearrangements around ~ 2 million base pairs adjacent to GULOP involving the KIF13B and MSRA genes. These data may suggest that genes acquiring deleterious mutations in the coding sequence may respond to these deleterious mutations with rapid substitution rates.

Evolutionary Changes in Primate Glutamate Dehydrogenases 1 and 2 Influence the Protein Regulation by Ligands, Targeting and Posttranslational Modifications.

There are two paralogs of glutamate dehydrogenase (GDH) in humans encoded by the GLUD1 and GLUD2 genes as a result of a recent retroposition during the evolution of primates. The two human GDHs possess significantly different regulation by allosteric ligands, which is not fully characterized at the structural level. Recent advances in identification of the GDH ligand binding sites provide a deeper perspective on the significance of the accumulated substitutions within the two GDH paralogs. In this review, we describe the evolution of GLUD1 and GLUD2 after the duplication event in primates using the accumulated sequencing and structural data. A new gibbon GLUD2 sequence questions the indispensability of ancestral R496S and G509A mutations for GLUD2 irresponsiveness to GTP, providing an alternative with potentially similar regulatory features. The data of both GLUD1 and GLUD2 evolution not only confirm substitutions enhancing GLUD2 mitochondrial targeting, but also reveal a conserved mutation in ape GLUD1 mitochondrial targeting sequence that likely reduces its transport to mitochondria. Moreover, the information of GDH interactors, posttranslational modification and subcellular localization are provided for better understanding of the GDH mutations. Medically significant point mutations causing deregulation of GDH are considered from the structural and regulatory point of view.

Comparative kinetics of humans and non-human primates during vertical climbing.

Climbing represents a critical behavior in the context of primate evolution. However, anatomically modern human populations are considered ill-suited for climbing. This adaptation can be attributed to the evolution of striding bipedalism, redirecting anatomical traits away from efficient climbing. Although prior studies have speculated on the kinetic consequences of this anatomical reorganization, there is a lack of data on the force profiles of human climbers. This study utilized high-speed videography and force plate analysis to assess single limb forces during climbing from 44 human participants of varying climbing experience and compared these data with climbing data from eight species of non-human primates (anthropoids and strepsirrhines). Contrary to expectations, experience level had no significant effect on the magnitude of single limb forces in humans. Experienced climbers did, however, demonstrate a predictable relationship between center of mass position and peak normal forces, suggesting a better ability to modulate forces during climbing. Humans exhibited significantly higher peak propulsive forces in the hindlimb compared with the forelimb and greater hindlimb dominance overall compared with non-human primates. All species sampled demonstrated exclusively tensile forelimbs and predominantly compressive hindlimbs. Strepsirrhines exhibited a pull-push transition in normal forces, while anthropoid primates, including humans, did not. Climbing force profiles are remarkably stereotyped across humans, reflecting the universal mechanical demands of this form of locomotion. Extreme functional differentiation between forelimbs and hindlimbs in humans may help to explain the evolution of bipedalism in ancestrally climbing hominoids.