Primate Evolution Research Articles

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.

Evolution of a Human-Specific De Novo Open Reading Frame and Its Linked Transcriptional Silencer.

In the human genome, two short open reading frames (ORFs) separated by a transcriptional silencer and a small intervening sequence stem from the gene SMIM45. The two ORFs show different translational characteristics, and they also show divergent patterns of evolutionary development. The studies presented here describe the evolution of the components of SMIM45. One ORF consists of an ultra-conserved 68 amino acid (aa) sequence, whose origins can be traced beyond the evolutionary age of divergence of the elephant shark, ~462 MYA. The silencer also has ancient origins, but it has a complex and divergent pattern of evolutionary formation, as it overlaps both at the 68 aa ORF and the intervening sequence. The other ORF consists of 107 aa. It develops during primate evolution but is found to originate de novo from an ancestral non-coding genomic region with root origins within the Afrothere clade of placental mammals, whose evolutionary age of divergence is ~99 MYA. The formation of the complete 107 aa ORF during primate evolution is outlined, whereby sequence development is found to occur through biased mutations, with disruptive random mutations that also occur but lead to a dead-end. The 107 aa ORF is of particular significance, as there is evidence to suggest it is a protein that may function in human brain development. Its evolutionary formation presents a view of a human-specific ORF and its linked silencer that were predetermined in non-primate ancestral species. The genomic position of the silencer offers interesting possibilities for the regulation of transcription of the 107 aa ORF. A hypothesis is presented with respect to possible spatiotemporal expression of the 107 aa ORF in embryonic tissues.

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.

Evolutionary continuity and divergence of auditory dorsal and ventral pathways in primates revealed by ultra-high field diffusion MRI

Auditory dorsal and ventral pathways in the human brain play important roles in supporting speech and language processing. However, the evolutionary root of the dual auditory pathways in the primate brain is unclear. By parcellating the auditory cortex of marmosets (a New World monkey species), macaques (an Old World monkey species), and humans using the same individual-based analysis method and tracking the pathways from the auditory cortex based on multi-shell diffusion-weighted MRI (dMRI), homologous auditory dorsal and ventral fiber tracks were identified in these primate species. The ventral pathway was found to be well conserved in all three primate species analyzed but extend to more anterior temporal regions in humans. In contrast, the dorsal pathway showed a divergence between monkey and human brains. First, frontal regions in the human brain have stronger connections to the higher-level auditory regions than to the lower-level auditory regions along the dorsal pathway, while frontal regions in the monkey brain show opposite connection patterns along the dorsal pathway. Second, the left lateralization of the dorsal pathway is only found in humans. Moreover, the connectivity strength of the dorsal pathway in marmosets is more similar to that of humans than macaques. These results demonstrate the continuity and divergence of the dual auditory pathways in the primate brains along the evolutionary path, suggesting that the putative neural networks supporting human speech and language processing might have emerged early in primate evolution.

Effects of binocular cue availability on leaping performance in Cheirogaleus medius: implications for primate origins.

Multiple competing hypotheses attribute the evolution of the suite of traits that distinguish primates from their closest relatives, including forward-facing eyes, which create a wide field of binocular vision, to specific behavioral and ecological factors. The grasp-leaping hypothesis suggests that the evolution of these traits in basal primates was driven by the demands of a form of leaping locomotion unique to primates. Whether the grasp-leaping hypothesis provides a viable mechanism for the evolution of primates' forward-facing eyes remains untested. To determine whether grasp-leaping locomotion may have contributed to driving the evolution of primates' forward-facing eyes, the importance of vision within the binocular field for this type of leaping was evaluated experimentally in Cheirogaleus medius, one of the cheirogaleid primate species considered reasonable living analogs of the earliest primates. Availability of binocular visual cues was experimentally restricted using a head-mounted blinder that narrowed the binocular visual field without altering the total visual field. Animals altered their launch behavior, reduced their horizontal leap speed, and were significantly more likely to select paths that offered the shortest available leaps when their binocular field was restricted. Restriction of binocular cue availability also significantly increased the probability of adverse landings even when statistically controlling for potentially confounding variables such as leap distance, horizontal leap speed, learning effects, etc. These results suggest a functional mechanism by which selection for improved grasp-leaping could also have contributed to the evolution of forward-facing eyes in the earliest crown primates.

Effect of binocular visual cue availability on fruit and insect grasping performance in two cheirogaleids: Implications for primate origins hypotheses

Forward-facing eyes with parallel optic axes, which provide a wide field of binocular vision and precise depth perception, are among the diagnostic features of crown primates; however, the adaptive significance of this feature remains contentious. Two of the most prominent primate-origins hypotheses propose that either foraging for fruit or nocturnal predation on insects created selective pressures that led to the evolution of diagnostic primate traits, including a wide binocular field. To determine whether either of these hypotheses provides a viable explanation for the evolution of primates' derived eye orientation, the importance of binocular depth cues for the two tasks invoked by these hypotheses was evaluated experimentally in Microcebus murinus and Cheirogaleus medius, cheirogaleids' considered reasonable living analogs of the earliest euprimates. Performance in grasping insects and fruit was evaluated when the animals made use of their full binocular visual field and when their binocular visual field was restricted using a helmet-mounted blinder. Restriction of the binocular field had no effect on fruit grasping performance; however, restriction of the binocular field resulted in a significant deficit in insect predation performance. Differences in behavioral variables also suggest that insect predation is a more visually demanding task than fruit foraging. These results support the role of insect predation, but not fruit foraging, in contributing to the selective pressures that led to the evolution of parallel optic axes and a wide binocular field in crown primates.

Divergent Evolutionary Rates of Primate Brain Regions as Revealed by Genomics and Transcriptomics.

Although the primate brain contains numerous functionally distinct structures that have experienced diverse genetic changes during the course of evolution and development, these changes remain to be explored in detail. Here we utilize two classic metrics from evolutionary biology, the evolutionary rate index (ERI) and the transcriptome age index (TAI), to investigate the evolutionary alterations that have occurred in each area and developmental stage of the primate brain. We observed a higher evolutionary rate for those genes expressed in the non-cortical areas during primate evolution, particularly in human, with the highest rate of evolution being exhibited at brain developmental stages between late infancy and early childhood. Further, the transcriptome age of the non-cortical areas was lower than that of the cerebral cortex, with the youngest age apparent at brain developmental stages between late infancy and early childhood. Our exploration of the evolutionary patterns manifest in each brain area and developmental stage provides important reference points for further research into primate brain evolution.

Integration-free induced pluripotent stem cells from three endangered Southeast Asian non-human primate species

Advanced molecular and cellular technologies provide promising tools for wildlife and biodiversity conservation. Induced pluripotent stem cell (iPSC) technology offers an easily accessible and infinite source of pluripotent stem cells, and have been derived from many threatened wildlife species. This paper describes the first successful integration-free reprogramming of adult somatic cells to iPSCs, and their differentiation, from three endangered Southeast Asian primates: the Celebes Crested Macaque (Macaca nigra), the Lar Gibbon (Hylobates lar), and the Siamang (Symphalangus syndactylus). iPSCs were also generated from the Proboscis Monkey (Nasalis larvatus). Differences in mechanisms could elicit new discoveries regarding primate evolution and development. iPSCs from endangered species provides a safety net in conservation efforts and allows for sustainable sampling for research and conservation, all while providing a platform for the development of further in vitro models of disease.

Tempo and mode of gene expression evolution in the brain across primates.

Primate evolution has led to a remarkable diversity of behavioral specializations and pronounced brain size variation among species (Barton, 2012; DeCasien and Higham, 2019; Powell et al., 2017). Gene expression provides a promising opportunity for studying the molecular basis of brain evolution, but it has been explored in very few primate species to date (e.g. Khaitovich et al., 2005; Khrameeva et al., 2020; Ma et al., 2022; Somel et al., 2009). To understand the landscape of gene expression evolution across the primate lineage, we generated and analyzed RNA-seq data from four brain regions in an unprecedented eighteen species. Here, we show a remarkable level of variation in gene expression among hominid species, including humans and chimpanzees, despite their relatively recent divergence time from other primates. We found that individual genes display a wide range of expression dynamics across evolutionary time reflective of the diverse selection pressures acting on genes within primate brain tissue. Using our samples that represent a 190-fold difference in primate brain size, we identified genes with variation in expression most correlated with brain size. Our study extensively broadens the phylogenetic context of what is known about the molecular evolution of the brain across primates and identifies novel candidate genes for the study of genetic regulation of brain evolution.

Quantitative assessment of grasping strength in platyrrhine monkeys.

Despite the longstanding importance of grasping adaptations in theories of primate evolution, quantitative data on primate grasping strength remain rare. We present the results of two studies testing the prediction that callitrichines-given their comparative retreat from a small-branch environment and specialization for movement and foraging on tree trunks and large boughs-should be characterized by weaker grasping forces and underdeveloped digital flexor muscles relative to other platyrrhines. First, we directly measured manual grasping strength in marmosets (Callithrix jacchus) and squirrel monkeys (Saimiri boliviensis), using a custom-constructed force transducer. Second, we reanalyzed existing datasets on the fiber architecture of forearm and leg muscles in 12 platyrrhine species, quantifying digital flexor muscle physiological cross-sectional area (i.e., PCSA, a morphometric proxy of muscle strength) relative to the summed PCSA across all forearm or leg muscles. Callithrix was characterized by lower mean and maximum grasping forces than Saimiri, and callitrichines as a clade were found to have relatively underdeveloped manual digital flexor muscle PCSA. However, relative pedal digital flexor PCSA did not significantly differ between callitrichines and other platyrrhines. We found partial support for the hypothesis that variation in predominant substrate usage explains variation in empirical measurements of and morphological correlates of grasping strength in platyrrhines. Future research should extend the work presented here by (1) collecting morphological and empirical metrics of grasping strength in additional primate taxa and (2) extending performance testing to include empirical measures of primate pedal grasping forces as well.

Scaling patterns of cortical folding and thickness in early human brain development in comparison with primates.

Across mammalia, brain morphology follows specific scaling patterns. Bigger bodies have bigger brains, with surface area outpacing volume growth, resulting in increased foldedness. We have recently studied scaling rules of cortical thickness, both local and global, finding that the cortical thickness difference between thick gyri and thin sulci also increases with brain size and foldedness. Here, we investigate early brain development in humans, using subjects from the Developing Human Connectome Project, scanned shortly after pre-term or full-term birth, yielding magnetic resonance images of the brain from 29 to 43 postmenstrual weeks. While the global cortical thickness does not change significantly during this development period, its distribution does, with sulci thinning, while gyri thickening. By comparing our results with our recent work on humans and 11 non-human primate species, we also compare the trajectories of primate evolution with human development, noticing that the 2 trends are distinct for volume, surface area, cortical thickness, and gyrification index. Finally, we introduce the global shape index as a proxy for gyrification index; while correlating very strongly with gyrification index, it offers the advantage of being calculated only from local quantities without generating a convex hull or alpha surface.

Deciphering the Role of Rapidly Evolving Conserved Elements in Primate Brain Development and Exploring Their Potential Involvement in Alzheimer's Disease.

Although previous studies have identified human-specific accelerated regions as playing a key role in the recent evolution of the human brain, the characteristics and cellular functions of rapidly evolving conserved elements (RECEs) in ancestral primate lineages remain largely unexplored. Here, based on large-scale primate genome assemblies, we identify 888 RECEs that have been highly conserved in primates that exhibit significantly accelerated substitution rates in the ancestor of the Simiiformes. This primate lineage exhibits remarkable morphological innovations, including an expanded brain mass. Integrative multiomic analyses reveal that RECEs harbor sequences with potential cis-regulatory functions that are activated in the adult human brain. Importantly, genes linked to RECEs exhibit pronounced expression trajectories in the adult brain relative to the fetal stage. Furthermore, we observed an increase in the chromatin accessibility of RECEs in oligodendrocytes from individuals with Alzheimer's disease (AD) compared to that of a control group, indicating that these RECEs may contribute to brain aging and AD. Our findings serve to expand our knowledge of the genetic underpinnings of brain function during primate evolution.

Deciphering Gorilla gorilla gorilla immunoglobulin loci in multiple genome assemblies and enrichment of IMGT resources.

Through the analysis of immunoglobulin genes at the IGH, IGK, and IGL loci from four Gorilla gorilla gorilla genome assemblies, IMGT® provides an in-depth overview of these loci and their individual variations in a species closely related to humans. The similarity between gorilla and human IG gene organization allowed the assignment of gorilla IG gene names based on their human counterparts. This study revealed significant findings, including variability in the IGH locus, the presence of known and new copy number variations (CNVs), and the accurate estimation of IGHG genes. The IGK locus displayed remarkable homogeneity and lacked the gene duplication seen in humans, while the IGL locus showed a previously unconfirmed CNV in the J-C cluster. The curated data from these analyses, available on the IMGT website, enhance our understanding of gorilla immunogenetics and provide valuable insights into primate evolution.

Guidelines and considerations for capturing and collaring wild primates: a case study with capuchin monkeys (Sapajus nigritus cucullatus).

Many aspects of the ecology, evolution and social behavior of wild-living primates remain un-explored and require further investigation. While long-term field studies are crucial for addressing conservation concerns for many primates' species, acquiring the necessary data is often challenging, often due to difficulties in locating study groups. Radio-telemetry has significantly facilitated the study of primates and other animals living in tropical forests. However, there are important practical challenges in the process of capturing and releasing animals after placement of telemetry collars. In this study, we report guidelines and considerations for capturing and collaring wild capuchin monkeys, Sapajus nigritus cucullatus, in the Atlantic Forest of Argentina. Our ultimate goal is to contribute to making captures safer, preventing harm and stress to animals when using radio-telemetry in monitoring strategies for conservation of this primate species. These methods can be useful for researchers using field capture and radio-telemetry for monitoring groups or populations of wild primates, specifically wild Sapajus.

Structural Evolution of Primate Glutamate Dehydrogenase 2 as Revealed by In Silico Predictions and Experimentally Determined Structures.

Glutamate dehydrogenase (GDH) interconverts glutamate to a-ketoglutarate and ammonia, interconnecting amino acid and carbohydrate metabolism. In humans, two functional GDH genes, GLUD1 and GLUD2, encode for hGDH1 and hGDH2, respectively. GLUD2 evolved from retrotransposition of the GLUD1 gene in the common ancestor of modern apes. These two isoenzymes are involved in the pathophysiology of human metabolic, neoplastic, and neurodegenerative disorders. The 3D structures of hGDH1 and hGDH2 have been experimentally determined; however, no information is available about the path of GDH2 structure changes during primate evolution. Here, we compare the structures predicted by the AlphaFold Colab method for the GDH2 enzyme of modern apes and their extinct primate ancestors. Also, we analyze the individual effect of amino acid substitutions emerging during primate evolution. Our most important finding is that the predicted structure of GDH2 in the common ancestor of apes was the steppingstone for the structural evolution of primate GDH2s. Two changes with a strong functional impact occurring at the first evolutionary step, Arg443Ser and Gly456Ala, had a destabilizing and stabilizing effect, respectively, making this step the most important one. Subsequently, GDH2 underwent additional modifications that fine-tuned its enzymatic properties to adapt to the functional needs of modern-day primate tissues.

The successive emergence ofERVL-MaLRs inprimates.

Although the ERVL-mammalian-apparent LTR retrotransposons (MaLRs) are the fourth largest family of transposable elements in the human genome, their evolutionary history and relationship have not been thoroughly studied. In this study, through RepeatMasker annotations of some representative species and construction of phylogenetic tree by sequence similarity, all primate-specific MaLR members are found to descend from MLT1A1 retrotransposon. Comparative genomic analysis, transposition-in-transposition inference, and sequence feature comparisons consistently show that each MaLR member evolved from its predecessor successively and had a limited activity period during primate evolution. Accordingly, a novel MaLR member was discovered as successor of MSTB1 in Tarsiiformes. At last, the identification of candidate precursor and intermediate THE1A elements provides further evidence for the previously proposed arms race model between ZNF430/ZNF100 and THE1B/THE1A. Taken together, this study sheds light on the evolutionary history of MaLRs and can serve as a foundation for future research on their interactions with zinc finger genes, gene regulation, and human health implications.

The relativity of ontogenetic time on primate evolution and the emergence of language

Most reviews on primatology focus on the similarities between the species of Pan (chimpanzees and bonobos) and Homo (sapiens) genera. In this paper, however, we review the literature on heterochronic differences in ontogenetic development of species in order to raise a discussion about their behavioral differences, particularly in relation to the human communication system. A key concept discussed here is neoteny, which refers to the slowed rate of species development. Human biology exhibits high levels of neoteny, resulting in a prolonged period of development during the first decade of postnatal life. Human neoteny enables the brain to develop in conjunction with physical and social environments, emphasizing that biology and society should not be perceived as distinct perspectives of the same process, but rather as interdependent processes that collaborate for the normal development of human beings. In order to identify biological concepts that may have contributed to the emergence of language, throughout this paper we explore how neoteny can be a potential explanatory concept to some of the behavioral differences between species, and how this may relate to cognitive systems such as language acquisition in Homo sapiens.

The evolution of bitter taste receptor gene in primates: Gene duplication and selection.

Bitter taste perception plays an important role in preventing animals from digesting poisonous and harmful substances. In primates, especially the Cercopithecidae species, most species feed on plants; thus, it is reasonable to speculate that most of the bitter taste receptor genes (T2Rs) of primates are under purifying selection to maintain the functional stability of bitter taste perception. Gene duplication has happened in T2Rs frequently, and what will be the fate of T2Rs copies is another question we are concerned about. To answer these questions, we selected the T2Rs of primates reported in another study and conducted corresponding selective pressure analyses to determine what kind of selective pressure was acting on them. Further, we carried out selective pressure analyses on gene copies and their corresponding ancestors by considering several possible situations. The results showed that among the 25 gene groups examined here, 15 groups are subject to purifying selection and others are under relaxed selection, with many positively selected sites detected. Gene copies existed in several groups, but only some groups (clade1_a1-b2, clade1_c-c2, clade1_d1-d3, clade1_f1-f2, T2R10, T2R13, and T2R42) have positively selected sites, inferring that they may have some relation to functional divergence. Taken together, T2Rs in primates are under diverse selective pressures, and most gene copies are subject to the same selective pressures. In such cases, the copies may be just to keep the function conservative, and more copies can increase the quantity of the bitter taste receptor, raise the efficiency of bitter substance recognition, and finally enhance the fitness of feeding during the evolutionary course of primates. This study can improve our understanding of T2Rs evolution in primates.

The macroevolutionary dynamics of activity pattern in mammals: Primates in context

Activity pattern has played a prominent role in discussions of primate evolutionary history. Most primates are either diurnal or nocturnal, but a small number are active both diurnally and nocturnally. This pattern—cathemerality—also occurs at low frequency across mammals. Using a large sample of mammalian species, this study evaluates two macroevolutionary hypotheses proposed to explain why cathemerality is less common than diurnality and nocturnality: 1) that cathemeral lineages have higher extinction probabilities (differential diversification) and 2) that transitions out of cathemerality are more frequent, making it a less persistent state (differential state persistence). Rates of speciation, extinction, and transition between character states were estimated using hidden-rates models applied to a phylogenetic tree containing 3013 mammals classified by activity pattern. The models failed to detect consistent differences in diversification dynamics among activity patterns, but there is strong support for differential state persistence. Transition rates out of cathemerality tend to be much higher than transition rates out of nocturnality. Transition rates out of diurnality are similar to those for cathemerality in most clades, with two important exceptions: diurnality is unusually persistent in anthropoid primates and sciurid rodents. These two groups combine very low rates of transition out of diurnality with high speciation rates. This combination has no parallels among cathemeral lineages, explaining why diurnality has become more common than cathemerality in mammals. Similarly, the combination of rates found in anthropoids is sufficient to explain the low relative frequency of cathemerality in primates, making it unnecessary to appeal to high extinction probabilities in cathemeral lineages in this clade. These findings support the hypothesis that the distribution of activity patterns across mammals has been influenced primarily by differential state persistence, whereas the effect of differential diversification appears to have been more idiosyncratic.