Modern theories of human evolution foreshadowed by Darwin's Descent of Man.

Charles Darwin's The Descent of Man, published 150 years ago, laid the grounds for scientific studies into human origins and evolution. Three of his insights have been reinforced by modern science. The first is that we share many characteristics (genetic, developmental, physiological, morphological, cognitive, and psychological) with our closest relatives, the anthropoid apes. The second is that humans have a talent for high-level cooperation reinforced by morality and social norms. The third is that we have greatly expanded the social learning capacity that we see already in other primates. Darwin's emphasis on the role of culture deserves special attention because during an increasingly unstable Pleistocene environment, cultural accumulation allowed changes in life history; increased cognition; and the appearance of language, social norms, and institutions.

Resources for functional genomic studies of health and development in nonhuman primates.

Primates display a wide range of phenotypic variation underlaid by complex genetically regulated mechanisms. The links among DNA sequence, gene function, and phenotype have been of interest from an evolutionary perspective, to understand functional genome evolution and its phenotypic consequences, and from a biomedical perspective to understand the shared and human-specific roots of health and disease. Progress in methods for characterizing genetic, transcriptomic, and DNA methylation (DNAm) variation is driving the rapid development of extensive omics resources, which are now increasingly available from humans as well as a growing number of nonhuman primates (NHPs). The fast growth of large-scale genomic data is driving the emergence of integrated tools and databases, thus facilitating studies of gene functionality across primates. This review describes NHP genomic resources that can aid in exploration of how genes shape primate phenotypes. It focuses on the gene expression trajectories across development in different tissues, the identification of functional genetic variation (including variants deleterious for protein function and regulatory variants modulating gene expression), and DNAm profiles as an emerging tool to understand the process of aging. These resources enable comparative functional genomics approaches to identify species-specific and primate-shared gene functionalities associated with health and development.

Multiple forms of selection shape reproductive isolation in a primate hybrid zone.

Speciation occurs when populations diverge and become reproductively isolated from each other. Natural selection is commonly accepted to play a large role in this process, and it has been widely assumed that reproductive isolation often results as a by-product of divergence driven by adaptation in allopatry. When such populations come into secondary contact, reinforcement can act to strengthen reproductive isolation, but the frequency and importance of this process are still unknown. Here, we explored genomic signatures of selection in allopatry and sympatry for loci associated with reproductive isolation using a natural primate hybrid zone. By analysing reduced-representation sequencing data, we quantified admixture and population structure across a howler monkey hybrid zone and examined the relationship between locus-specific differentiation and introgression. We detected extensive admixture that was mostly limited to the narrow contact zone. Loci with reduced introgression into the heterospecific genomic background (the pattern expected for loci associated with reproductive isolation due to selection against hybrids) were significantly more differentiated between allopatric parental populations than loci with neutral and increased introgression, supporting the hypothesis that reproductive isolation is a by-product of divergence in allopatry. Further, loci with reduced introgression showed greater differentiation in sympatry than in allopatry, suggesting a role for reinforcement. Thus, our results reflect multiple forms of selection that have shaped reproductive isolation in this system. We conclude that reproductive isolation may have initially been driven by divergence in allopatry, but later reinforced by divergent selection in sympatry.

Do Mid-Crown Enamel Formation Front Angles Reflect Factors Linked to the Pace of Primate Growth and Development?

Enamel formation front (EFF) angles represent the leading edge of enamel matrix secretion at particular points in time. These angles are influenced by rates of enamel extension (the rates at which tooth crowns grow in height), rates of enamel matrix secretion and the angles that prisms make with the enamel-dentine junction. Previous research suggests, but has not yet established, that these angles reflect aspects of primate biology related to their pace of growth and development, most notably brain and body size. The present study tested this possibility on histological sections using phylogenetically-controlled and Bonferroni-corrected analyses spanning a broad taxonomic range. Ten species were represented in the analysis of anterior teeth; 17 in the analysis of posterior (postcanine) teeth (with varying sample sizes). Also, tested was the relationship of EFF angles to striae of Retzius periodicity (long period growth rhythms in enamel) and degree of folivory, as both factors are related to primate developmental rates. Finally, several analyses were conducted to investigate whether tooth size (operationalized as EDJ length) might mediate these relationships. Central results are as follows: (1) Relationships between EFF angles and brain weight (anterior teeth) and between EFF angles and body mass (anterior and posterior teeth) are statistically significant and (2) Mid-crown EFF angles are not statistically significantly related to EDJ lengths. These results suggest that tooth size does not mediate relationships between EFF angles and brain weight/body mass and are discussed with respect to underlying enamel growth variables (especially rates of enamel extension and secretion). Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 301:125-139, 2018. © 2017 Wiley Periodicals, Inc.

Infectious Diseases in Free-Ranging Blonde Capuchins, Sapajus flavius, in Brazil

The main threats to primates worldwide are the degradation, fragmentation,and loss of their habitats; hunting (especially for bushmeat); and illegal trade.For many species, the most important threat is forest fragmentation, resulting in small populations that are restricted to isolated forest patches. In this situation, primates are particularly vulnerable to disease. The Endangered blonde capuchin (Sapajus flavius) is now restricted to a few forest patches in Northeast Brazil. We investigated the occurrence of parasites and bacterial diseases in one of three free-ranging groups of S. flavius in a small forest patch in Paraíba state, Northeast Brazil. We tested for antibodies against Leishmania spp., Trypanosoma cruzi, Toxoplasma gondii, Leptospira spp. (24 strains), and Brucella spp.. We used molecular analysis to detect Plasmodium spp., and evaluated blood smears for the presence of hemoparasites. All individuals tested negative for Leptospira spp. and B. abortus, but 8 of 48 (16%) presented antibodies for both Leishmania spp. and T. cruzi. We identified antibodies to T. gondii in 12% of the individuals tested. Plasmodium brasilianum infection was present in 4% of the individuals tested, and blood smears showed microfilariae parasites in 46% of the individuals tested...

Hormones and Human and Nonhuman Primate Growth.

The aim of this paper was to review information pertaining to the hormonal regulation of nonhuman primate growth, with specific focus on the growth hormone (GH)-insulin-like growth factor (IGF) axis and adrenal androgens. Hormones of the GH-IGF axis are consistently associated with measures of growth - linear, weight, or both - during the growth period; in adulthood, concentrations of IGF-I, IGF-binding protein-3, and GH-binding protein are not associated with any measures of size. Comparing patterns of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) may be especially relevant for understanding whether the childhood stage of growth and development is unique to humans and perhaps other apes. Genetic, hormonal, and morphological data on adrenarche in other nonhuman primate species suggest that this endocrine transition is delayed in humans, chimpanzees, and possibly gorillas, while present very early in postnatal life in macaques. This suggests that although perhaps permitted by an extension of the pre-adolescent growth period, childhood builds upon existing developmental substrates rather than having been inserted de novo into an ancestral growth trajectory. Hormones can provide insight regarding the evolution of the human growth trajectory.

Consequences of early adverse rearing experience(EARE) on development: insights from non-human primate studies.

Early rearing experiences are important in one's whole life, whereas early adverse rearing experience(EARE) is usually related to various physical and mental disorders in later life. Although there were many studies on human and animals, regarding the effect of EARE on brain development, neuroendocrine systems, as well as the consequential mental disorders and behavioral abnormalities, the underlying mechanisms remain unclear. Due to the close genetic relationship and similarity in social organizations with humans, non-human primate(NHP) studies were performed for over 60 years. Various EARE models were developed to disrupt the early normal interactions between infants and mothers or peers. Those studies provided important insights of EARE induced effects on the physiological and behavioral systems of NHPs across life span, such as social behaviors(including disturbance behavior, social deficiency, sexual behavior, etc), learning and memory ability, brain structural and functional developments(including influences on neurons and glia cells, neuroendocrine systems, e.g., hypothalamic-pituitary-adrenal(HPA) axis, etc). In this review, the effects of EARE and the underlying epigenetic mechanisms were comprehensively summarized and the possibility of rehabilitation was discussed.

Human Oocyte-Derived Methylation Differences Persist in the Placenta Revealing Widespread Transient Imprinting.

Thousands of regions in gametes have opposing methylation profiles that are largely resolved during the post-fertilization epigenetic reprogramming. However some specific sequences associated with imprinted loci survive this demethylation process. Here we present the data describing the fate of germline-derived methylation in humans. With the exception of a few known paternally methylated germline differentially methylated regions (DMRs) associated with known imprinted domains, we demonstrate that sperm-derived methylation is reprogrammed by the blastocyst stage of development. In contrast a large number of oocyte-derived methylation differences survive to the blastocyst stage and uniquely persist as transiently methylated DMRs only in the placenta. Furthermore, we demonstrate that this phenomenon is exclusive to primates, since no placenta-specific maternal methylation was observed in mouse. Utilizing single cell RNA-seq datasets from human preimplantation embryos we show that following embryonic genome activation the maternally methylated transient DMRs can orchestrate imprinted expression. However despite showing widespread imprinted expression of genes in placenta, allele-specific transcriptional profiling revealed that not all placenta-specific DMRs coordinate imprinted expression and that this maternal methylation may be absent in a minority of samples, suggestive of polymorphic imprinted methylation.

Prenatal Brain-Body Allometry in Mammals.

Variation in relative brain size among adult mammals is produced by different patterns of brain and body growth across ontogeny. Fetal development plays a central role in generating this diversity, and aspects of prenatal physiology such as maternal relative metabolic rate, altriciality, and placental morphology have been proposed to explain allometric differences in neonates and adults. Primates are also uniquely encephalized across fetal development, but it remains unclear when this pattern emerges during development and whether it is common to all primate radiations. To reexamine these questions across a wider range of mammalian radiations, data on the primarily fetal rapid growth phase (RGP) of ontogenetic brain-body allometry was compiled for diverse primate (np = 12) and nonprimate (nnp = 16) mammalian species, and was complemented by later ontogenetic data in 16 additional species (np = 9; nnp = 7) as well as neonatal proportions in a much larger sample (np = 38; nnp = 83). Relative BMR, litter size, altriciality, and placental morphology fail to predict RGP slopes as would be expected if physiological and life history variables constrained fetal brain growth, but are associated with differences in birth timing along allometric trajectories. Prenatal encephalization is shared by all primate radiations, is unique to the primate Order, and is characterized by: (1) a robust change in early embryonic brain/body proportions, and (2) higher average RGP allometric slopes due to slower fetal body growth. While high slopes are observed in several nonprimate species, primates alone exhibit an intercept shift at 1 g body size. This suggests that primate prenatal encephalization is a consequence of early changes to embryonic neural and somatic tissue growth in primates that remain poorly understood.

Evolutionary modeling and correcting for observation error support a 3/5 brain-body allometry for primates.

The tight brain-body allometry across mammals and primates has motivated and informed many hypotheses about brain evolution in humans and other taxa. While a 2/3 or a 3/4 scaling is often at the core of such research, such exponents are derived from estimates based on particular statistical and evolutionary assumptions without careful consideration of how either may influence findings. Here we quantify primate brain-body allometry using phylogenetic comparative methods based on models of both adaptive and constrained evolution, and estimate and account for observational error in both response and predictor variables. Our results supported an evolutionary model in which brain size is directly constrained to evolve in unison with body size, rather than adapting to changes in the latter. The effects of controlling for phylogeny and observation error were substantial, and our analysis yielded a novel 3/5 scaling exponent for primate brain-body evolutionary allometry. Using this exponent with the latest brain- and body-size estimates to calculate new encephalization quotients for apes, humans, and fossil hominins, we found early hominins were substantially more encephalized than previously thought.

Life history, cognition and the evolution of complex foraging niches.

Animal species that live in complex foraging niches have, in general, improved access to energy-rich and seasonally stable food sources. Because human food procurement is uniquely complex, we ask here which conditions may have allowed species to evolve into such complex foraging niches, and also how niche complexity is related to relative brain size. To do so, we divided niche complexity into a knowledge-learning and a motor-learning dimension. Using a sample of 78 primate and 65 carnivoran species, we found that two life-history features are consistently correlated with complex niches: slow, conservative development or provisioning of offspring over extended periods of time. Both act to buffer low energy yields during periods of learning, and may thus act as limiting factors for the evolution of complex niches. Our results further showed that the knowledge and motor dimensions of niche complexity were correlated with pace of development in primates only, and with the length of provisioning in only carnivorans. Accordingly, in primates, but not carnivorans, living in a complex foraging niche requires enhanced cognitive abilities, i.e., a large brain. The patterns in these two groups of mammals show that selection favors evolution into complex niches (in either the knowledge or motor dimension) in species that either develop more slowly or provision their young for an extended period of time. These findings help to explain how humans constructed by far the most complex niche: our ancestors managed to combine slow development (as in other primates) with systematic provisioning of immatures and even adults (as in carnivorans). This study also provides strong support for the importance of ecological factors in brain size evolution.

Bone morphologies and histories: Life course approaches in bioarchaeology.

The duality of the skeleton as both a biological and cultural entity has formed the theoretical basis of bioarchaeology. In recent years bioarchaeological studies have stretched the early biocultural concept with the adoption of life course approaches in their study design and analyses, making a significant contribution to how we think about the role of postnatal plasticity. Life course theory is a conceptual framework used in several scientific fields of biology and the social sciences. Studies that emphasize life course approaches in the examination of bone morphology in the past are united in their interrogation of human life as a result of interrelated and cumulative events over not only the timeframe of individuals, but also over generations at the community level. This article provides an overview of the theoretical constructs that utilize the life course concept, and a discussion of the different ways these theories have been applied to thinking about trajectories of bone morphology in the past, specifically highlighting key recent studies that have used life course approaches to understand the influence of growth, stress, diet, activity, and aging on the skeleton. The goal of this article is to demonstrate the scope of contemporary bioarchaeological studies that illuminate the importance of environmental and behavioral influence on bone morphology. Understanding how trajectories of bone growth and morphology can be altered and shaped over the life course is critical not only for bioarchaeologists, but also researchers studying bone morphology in living nonhuman primates and fossil primate skeletons.

Dental maturation, eruption, and gingival emergence in the upper jaw of newborn primates.

In this report we provide data on dental eruption and tooth germ maturation at birth in a large sample constituting the broadest array of non-human primates studied to date. Over 100 perinatal primates, obtained from natural captive deaths, were screened for characteristics indicating premature birth, and were subsequently studied using a combination of histology and micro-CT. Results reveal one probable unifying characteristic of living primates: relatively advanced maturation of deciduous teeth and M1 at birth. Beyond this, there is great diversity in the status of tooth eruption and maturation (dental stage) in the newborn primate. Contrasting strategies in producing a masticatory battery are already apparent at birth in strepsirrhines and anthropoids. Results show that dental maturation and eruption schedules are potentially independently co-opted as different strategies for attaining feeding independence. The most common strategy in strepsirrhines is accelerating eruption and the maturation of the permanent dentition, including replacement teeth. Anthropoids, with only few exceptions, accelerate mineralization of the deciduous teeth, while delaying development of all permanent teeth except M1. These results also show that no living primate resembles the altricial tree shrew (Tupaia) in dental development. Our preliminary observations suggest that ecological explanations, such as diet, provide an explanation for certain morphological variations at birth. These results confirm previous work on perinatal indriids indicating that these and other primates telegraph their feeding adaptations well before masticatory anatomy is functional. Quantitative analyses are required to decipher specific dietary and other influences on dental size and maturation in the newborn primate.

Unraveling the Tangled Skein: The Evolution of Transcriptional Regulatory Networks in Development.

The molecular and genetic basis for the evolution of anatomical diversity is a major question that has inspired evolutionary and developmental biologists for decades. Because morphology takes form during development, a true comprehension of how anatomical structures evolve requires an understanding of the evolutionary events that alter developmental genetic programs. Vast gene regulatory networks (GRNs) that connect transcription factors to their target regulatory sequences control gene expression in time and space and therefore determine the tissue-specific genetic programs that shape morphological structures. In recent years, many new examples have greatly advanced our understanding of the genetic alterations that modify GRNs to generate newly evolved morphologies. Here, we review several aspects of GRN evolution, including their deep preservation, their mechanisms of alteration, and how they originate to generate novel developmental programs.

Evo-devo and the primate isocortex: the central organizing role of intrinsic gradients of neurogenesis.

Spatial gradients in the initiation and termination of basic processes, such as cytogenesis, cell-type specification and dendritic maturation, are ubiquitous in developing nervous systems. Such gradients can produce a niche adaptation in a particular species. For example, the high density of photoreceptors and neurons in the 'area centralis' of some vertebrate retinas result from the early maturation of its center relative to its periphery. Across species, regularities in allometric scaling of brain regions can derive from conserved spatial gradients: longer neurogenesis in the alar versus the basal plate of the neural tube is associated with relatively greater expansion of alar plate derivatives in larger brains. We describe gradients of neurogenesis within the isocortex and their effects on adult cytoarchitecture within and across species. Longer duration of neurogenesis in the caudal isocortex is associated with increased neuron number and density per column relative to the rostral isocortex. Later-maturing features of single neurons, such as soma size and dendritic spine numbers reflect this gradient. Considering rodents and primates, the longer the duration of isocortical neurogenesis in each species, the greater the rostral-to-caudal difference in neuron number and density per column. Extended developmental duration produces substantial, predictable changes in the architecture of the isocortex in larger brains, and presumably a progressively changed functional organization, the properties of which we do not yet fully understand. Many features of isocortical architecture previously viewed as species- or niche-specific adaptations can now be integrated as the natural outcomes of spatiotemporal gradients that are deployed in larger brains.

Growth of alveoli during postnatal development in humans based on stereological estimation.

Alveolarization in humans and nonhuman primates begins during prenatal development. Advances in stereological counting techniques allow accurate assessment of alveolar number; however, these techniques have not been applied to the developing human lung. Based on the recent American Thoracic Society guidelines for stereology, lungs from human autopsies, ages 2 mo to 15 yr, were fractionated and isometric uniform randomly sampled to count the number of alveoli. The number of alveoli was compared with age, weight, and height as well as growth between right and left lungs. The number of alveoli in the human lung increased exponentially during the first 2 yr of life but continued to increase albeit at a reduced rate through adolescence. Alveolar numbers also correlated with the indirect radial alveolar count technique. Growth curves for human alveolarization were compared using historical data of nonhuman primates and rats. The alveolar growth rate in nonhuman primates was nearly identical to the human growth curve. Rats were significantly different, showing a more pronounced exponential growth during the first 20 days of life. This evidence indicates that the human lung may be more plastic than originally thought, with alveolarization occurring well into adolescence. The first 20 days of life in rats implies a growth curve that may relate more to prenatal growth in humans. The data suggest that nonhuman primates are a better laboratory model for studies of human postnatal lung growth than rats.

Genes, development, and evolvability in primate evolution.

Development is the process whereby a fertilized cell becomes a mature individual. In metazoans, this complex process involves the differentiation of somatic cells into committed cell and tissue types; the organization and migration of cells, tissues, and anatomical structures relative to one another; and growth. Development matters to evolution in two ways. First, development carries out heritable genetic instructions contained in zygotes to produce functioning yet phenotypically varied individuals. At the population level, this variation in form and function among individuals provides the "raw material" for evolution. Second, the mechanisms of development influence the magnitude, direction, and interdependence of heritable phenotypic variation among traits. Together with phenomena such as genetic drift, organismal development determines the raw material available to selection and thus influences the rate and direction of phenotypic evolution.

The anatomy and ontogeny of the head, neck, pectoral, and upper limb muscles of Lemur catta and Propithecus coquereli (primates): discussion on the parallelism between ontogeny and phylogeny and implications for evolutionary and developmental biology.

Most anatomical studies of primates focus on skeletal tissues, but muscular anatomy can provide valuable information about phylogeny, functional specializations, and evolution. Herein, we present the first detailed description of the head, neck, pectoral, and upper limb muscles of the fetal lemuriforms Lemur catta (Lemuridae) and Propithecus coquereli (Indriidae). These two species belong to the suborder Strepsirrhini, which is often presumed to possess some plesiomorphic anatomical features within primates. We compare the muscular anatomy of the fetuses with that of infants and adults and discuss the evolutionary and developmental implications. The fetal anatomy reflects a phylogenetically more plesiomorphic condition in nine of the muscles we studied and a more derived condition in only two, supporting a parallel between ontogeny and phylogeny. The derived exceptions concern muscles with additional insertions in the fetus which are lost in adults of the same species, that is, flexor carpi radialis inserts on metacarpal III and levator claviculae inserts on the clavicle. Interestingly, these two muscles are involved in movements of the pectoral girdle and upper limb, which are mainly important for activities in later stages of life, such as locomotion and prey capture, rather than activities in fetal life. Accordingly, our findings suggest that some exceptions to the "ontogeny parallels phylogeny" rule are probably driven more by ontogenetic constraints than by adaptive plasticity.