Generation of transgenic monkeys with human inherited genetic disease

Modeling human diseases using nonhuman primates including chimpanzee, rhesus, cynomolgus, marmoset and squirrel monkeys has been reported in the past decades. Due to the high similarity between nonhuman primates and humans, including genome constitution, cognitive behavioral functions, anatomical structure, metabolic, reproductive, and brain functions; nonhuman primates have played an important role in understanding physiological functions of the human body, clarifying the underlying mechanism of human diseases, and the development of novel treatments for human diseases. However, nonhuman primate research has been restricted to cognitive, behavioral, biochemical and pharmacological approaches of human diseases due to the limitation of gene transfer technology in nonhuman primates. The recent advancement in transgenic technology that has led to the generation of the first transgenic monkey in 2001 and a transgenic monkey model of Huntington’s disease (HD) in 2008 has changed that focus. The creation of transgenic HD monkeys that replicate key pathological features of human HD patients further suggests the crucial role of nonhuman primates in the future development of biomedicine. These successes have opened the door to genetic manipulation in nonhuman primates and a new era in modeling human inherited genetic disorders. We focused on the procedures in creating transgenic Huntington’s disease monkeys, but our work can be applied to transgenesis in other nonhuman primate species.     

Locomotor adaptations within the Cercopithecus Genus: a multivariate approach.

Multivariate analysis as a technique for investigating locomotor differentiation among primates has proven its power and usefulness in many studies on various skeletal dimensions. In these analyses primate genera were distributed and sometimes clustered in a manner that was interpretable based on current knowledge of gross locomotor differences. In an effort to advance our understanding of arboreality and terrestriality in primates, the present research involves a careful look for the most subtle morphological differences in locomotor behavior. It is believed that by looking at such subtle shape differences an understanding of what it means morphologically for a primate to be either more or less arboreal may be achieved. The species within the primate genus Cercopithecus were analyzed. This genus includes species which may be placed along a habitat (ground-living to tree-dwelling) or activity spectrum. The different habitats or activity patterns clearly require slight variations in patterns of movement, which in turn may require subtle structural adaptations. Multivariate analyses of 67 postcranial variables on seven species within the genus allowed detection of slight degrees of morphological variation. However, when morphological differences are small, size variance among specimens may take on an inflated importance. A substantial amount of work was devoted to finding the least biased method of removing size variance from the variables while incorporating a discrete size variable into the study. Using these transformed skeletal variables, interspecific groupings were discovered. Much of this infrastructure is then related to differing locomotor behavior and provides an insight into the fine structure of primate locomotor adaptation in an arboreal habitat.     

Timing and tempo of primate speciation

Published molecular clocks for primates are used to estimate typical divergence times for phylogroups (1.6 Ma), species (3.3 Ma), sister species (2.7 Ma), genera (8.9 Ma) and sister genera (8.6 Ma). Significant median differences exist between major groups (infraorders and superfamilies) for various divergence times. These data are employed to estimate typical maximum duration of speciation. Typical primate values (1.1 Ma) suggest this process to be faster than is characteristic of many vertebrates. However, after considering divergence times for hybridizing congeneric and confamilial primates, this value is likely only to estimate the commencement of prezygotic isolating mechanisms, rather than the completion of reproductive isolation. Thus, speciation typically takes around 1.0 Ma to more than 4.0 Ma to occur, depending on whether prezygotic or post-zygotic isolating mechanisms are emphasized. Typical primate genus age is around 5.3 Ma, but we note differences among major groups. In light of these estimates, the classification of humans and chimpanzees is reconsidered using a molecular yardstick approach. Three taxonomic frameworks may flow from molecular analyses, all of them having major implications for understanding the evolution of humans and chimpanzees.     

Primate vocal communication: a useful tool for understanding human speech and language evolution?

Language is a uniquely human trait, and questions of how and why it evolved have been intriguing scientists for years. Nonhuman primates (primates) are our closest living relatives, and their behavior can be used to estimate the capacities of our extinct ancestors. As humans and many primate species rely on vocalizations as their primary mode of communication, the vocal behavior of primates has been an obvious target for studies investigating the evolutionary roots of human speech and language. By studying the similarities and differences between human and primate vocalizations, comparative research has the potential to clarify the evolutionary processes that shaped human speech and language. This review examines some of the seminal and recent studies that contribute to our knowledge regarding the link between primate calls and human language and speech. We focus on three main aspects of primate vocal behavior: functional reference, call combinations, and vocal learning. Studies in these areas indicate that despite important differences, primate vocal communication exhibits some key features characterizing human language. They also indicate, however, that some critical aspects of speech, such as vocal plasticity, are not shared with our primate cousins. We conclude that comparative research on primate vocal behavior is a very promising tool for deepening our understanding of the evolution of human speech and language, but much is still to be done as many aspects of monkey and ape vocalizations remain largely unexplored.     

Estimating the phylogeny and divergence times of primates using a supermatrix approach

Background  

The primates are among the most broadly studied mammalian orders, with the published literature containing extensive analyses of their behavior, physiology, genetics and ecology. The importance of this group in medical and biological research is well appreciated, and explains the numerous molecular phylogenies that have been proposed for most primate families and genera. Composite estimates for the entire order have been infrequently attempted, with the last phylogenetic reconstruction spanning the full range of primate evolutionary relationships having been conducted over a decade ago.     

Characterization of the fecal microbiome from non-human wild primates reveals species specific microbial communities

Background

Host-associated microbes comprise an integral part of animal digestive systems and these interactions have a long evolutionary history. It has been hypothesized that the gastrointestinal microbiome of humans and other non-human primates may have played significant roles in host evolution by facilitating a range of dietary adaptations. We have undertaken a comparative sequencing survey of the gastrointestinal microbiomes of several non-human primate species, with the goal of better understanding how these microbiomes relate to the evolution of non-human primate diversity. Here we present a comparative analysis of gastrointestinal microbial communities from three different species of Old World wild monkeys.

Methodology/Principal Findings

We analyzed fecal samples from three different wild non-human primate species (black-and-white colobus [Colubus guereza], red colobus [Piliocolobus tephrosceles], and red-tailed guenon [Cercopithecus ascanius]). Three samples from each species were subjected to small subunit rRNA tag pyrosequencing. Firmicutes comprised the vast majority of the phyla in each sample. Other phyla represented were Bacterioidetes, Proteobacteria, Spirochaetes, Actinobacteria, Verrucomicrobia, Lentisphaerae, Tenericutes, Planctomycetes, Fibrobacateres, and TM7. Bray-Curtis similarity analysis of these microbiomes indicated that microbial community composition within the same primate species are more similar to each other than to those of different primate species. Comparison of fecal microbiota from non-human primates with microbiota of human stool samples obtained in previous studies revealed that the gut microbiota of these primates are distinct and reflect host phylogeny.

Conclusion/Significance

Our analysis provides evidence that the fecal microbiomes of wild primates co-vary with their hosts, and that this is manifested in higher intraspecies similarity among wild primate species, perhaps reflecting species specificity of the microbiome in addition to dietary influences. These results contribute to the limited body of primate microbiome studies and provide a framework for comparative microbiome analysis between human and non-human primates as well as a comparative evolutionary understanding of the human microbiome.     

Moving primate genomics beyond the chimpanzee genome

The comparative DNA sequence data that already exist on individual genomic loci depict the phylogenetic relationships of nearly all extant primate genera. Such a phylogenetic representation of the primates, validated by many sequenced primate genomes, and encompassing the full adaptive diversity of the order, is a prerequisite for identifying the genetic basis of humankind, and for testing the proposed human uniqueness of these traits. Some of these traits have been discovered recently, particularly in genes encoding proteins that are important for brain function.     

The social structure of primates

A comprehensive comparative study of the social structure of primates revealed: There is no social structure which can be considered typical and discriminative for primates. The varying social structures of the extant primate genera cannot be derived from each other: In contrast it seems that the basic, ancestral condition was that of solitary living animals, loosely aggregated. It can be assumed that the development to a gregarious society took place in two entirely different ways. In terms of primate phylogeny this different development can be shown for the prosimians as well as for the old world and new world monkeys as independently occurring processes. One way of behavioral specialization resulted in close pair bonds or in small family groups, whereas the other led to female groups. The presupposition for the forming of a society based on female groups is the close contact between the individuals and in addition to this, a remarkable social tolerance of females to each other. Social specializations which can be considered transitional from the basic condition are frequently found in prosimians. The kinds of social structures of the particular genera are in close relation to their taxonomic positions in the phylogenetic scala. The number of males in larger social groups of primates is substantially irrelevant as the groups are socially most dependent on the females. The protecting males are socially peripheral. The social units of most of the primate species are matrilocal and endure for several generations. In contrast, the social units of the gibbons and of the pongids are patrilocal and are established anew by the females in each generation. Consequently the social unit disintegrates on the death of the male. In all genera studied, male and female individuals present considerable behavioral differences which can be found even in juveniles. Primates are able to discriminate well known and confident individuals from other less confident; they prefer more confident individuals to less confident ones, and less confident to non-confident. As a consequence of this discriminative ability there is a clear preference for near when compared to distant relatives. The complexity of the social relations is brought about by this ability to discriminate combined with the longevity of primates. This is a characteristic and discriminative feature of the primate order. Dominance relations occur in every social group of primates. Linear hierarchies of dominance have been developed only once in prosimians (Lemur) and also once in simians (Cercopithecinae). Therefore, liner hierarchies are not typical for primates.     

The Implications of Primate Behavioral Flexibility for Sustainable Human–Primate Coexistence in Anthropogenic Habitats

People are an inescapable aspect of most environments inhabited by nonhuman primates today. Consequently, interest has grown in how primates adjust their behavior to live in anthropogenic habitats. However, our understanding of primate behavioral flexibility and the degree to which it will enable primates to survive alongside people in the long term remains limited. This Special Issue brings together a collection of papers that extend our knowledge of this subject. In this introduction, we first review the literature to identify past and present trends in research and then introduce the contributions to this Special Issue. Our literature review confirms that publications on primate behavior in anthropogenic habitats, including interactions with people, increased markedly since the 2000s. Publications concern a diversity of primates but include only 17% of currently recognized species, with certain primates overrepresented in studies, e.g., chimpanzees and macaques. Primates exhibit behavioral flexibility in anthropogenic habitats in various ways, most commonly documented as dietary adjustments, i.e., incorporation of human foods including agricultural crops and provisioned items, and as differences in activity, ranging, grouping patterns, and social organization, associated with changing anthropogenic factors. Publications are more likely to include information on negative rather than positive or neutral interactions between humans and primates. The contributions to this Special Issue include both empirical research and reviews that examine various aspects of the human–primate interface. Collectively, they show that primate behavior in shared landscapes does not always conflict with human interests, and demonstrate the value of examining behavior from a cost–benefit perspective without making prior assumptions concerning the nature of interactions. Careful interdisciplinary research has the potential to greatly improve our understanding of the complexities of human–primate interactions, and is crucial for identifying appropriate mechanisms to enable sustainable human–primate coexistence in the 21st century and beyond.     

The strange blood: natural hybridization in primates

Hybridization between two closely related species is a natural evolutionary process that results in an admixture of previously isolated gene pools. The exchange of genes between species may accelerate adaptation and lead to the formation of new lineages. Hybridization can be regarded as one important evolutionary mechanism driving speciation processes. Although recent studies have highlighted the taxonomic breadth of natural hybridization in the primate order, information about primate hybridization is still limited compared to that about the hybridization of fish, birds, or other mammals. In primates, hybridization has occurred mainly between subspecies and species, but has also been detected between genera and even in the human lineage. Here we provide an overview of cases of natural hybridization in all major primate radiations. Our review emphasizes a phylogenetic approach. We use the data presented to discuss the impact of hybridization on taxonomy and conservation.     

Primate sociality in evolutionary context

Much work has been done to further our understanding of the mechanisms that underlie the diversity of primate social organizations, but none has addressed the limits to that diversity or the question of what causes species to either form or not form social networks. The fact that all living primates typically live in social networks makes it highly likely that the last common ancestor of living primates already lived in social networks, and that sociality formed an integral part of the adaptive nature of primate origins. A characterization of primate sociality within the wider mammalian context is therefore essential to further our understanding of the adaptive nature of primate origins. Here we determine correlates of sociality and nonsociality in rodents as a model to infer causes of sociality in primates. We found sociality to be most strongly associated with large-bodied arboreal species that include a significant portion of fruit in their diet. Fruits and other plant products, such as flowers, seeds, and young leaves, are patchily distributed in time and space and are therefore difficult to find. These food resources are, however, predictable and dependable when their location is known. Hence, membership in a social unit can maximize food exploitation if information on feeding sites is shared. Whether sociality evolved in the primate stem lineage or whether it was already present earlier in the evolution of Euarchontoglires remains uncertain, although tentative evidence points to the former scenario. In either case, frugivory is likely to have played an important role in maintaining the presence of a social lifestyle throughout primate evolution.     

Ecological correlates of trophic status and frugivory in neotropical primates

Primates are among the most observable and best studied vertebrate order in tropical forest regions, with widespread attention dedicated to the feeding ecology of wild populations. In particular, primates play a key role as frugivores and seed‐dispersal agents for a myriad of tropical plants. Sampling effort by primatologists, however, has been unequally distributed, hampering quantitative comparisons of primate diets. We provide the first systematic review of primate diets, with an emphasis on frugivory, using a comprehensive compilation of 290 unique primate dietary studies from 164 localities in 17 countries across the entire Neotropical realm. We account for sampling effort (standardised as hours) in comparing the richness of fruiting plants recorded in primate diets, and the relative contribution of frugivory to the overall diet in relation to key life‐history traits, such as body mass. We find strong support for the long‐held hypothesis, based on Kay's Threshold, that body size imposes an upper limit on insectivory and a lower limit on folivory, and therefore that frugivory is most important at intermediate body sizes. However, the upper body mass limit of extant neotropical primates, truncated by the post‐Pleistocene megafaunal overkill, has implications for the extent of the frugivory–folivory continuum in extinct lineages. Contemporary threats faced by the largest primates serve as a further warning that the feeding ecology and diet of all neotropical primates remain severely undersampled with regard to the composition and richness of fruits consumed. Indeed, frugivorous primates expected to have the most species‐rich plant diets are amongst those most poorly sampled, exposing implications for our current understanding of primate–plant interaction networks.     

Parent–Offspring Conflict in Primates

Parent–offspring conflict (POC) theory (Trivers, 1974) has stimulated controversy in evolutionary biology and behavioral ecology. The theory has been criticized by some primate behavioral researchers on both conceptual and empirical grounds. First, it has been argued that it would be more advantageous to mothers and offspring to agree over the allocation of parental investment and to cooperate rather than to disagree and engage in conflict. Second, some studies have provided data suggesting that primate mothers and offspring engage in behavioral conflict over the scheduling of their activities rather than parental investment. In reality, parent–offspring interactions are likely to involve both cooperation and conflict, and the hypothesis that mothers and infants squabble over the scheduling of their activities is not incompatible with POC theory. Furthermore, the predictions of POC theory are supported by a number of empirical studies of primates. POC theory has enhanced our understanding of the dynamics of parent–offspring relationships in many animal species, and it is very likely that future studies of primates will continue to benefit from using POC theory as an explanatory framework.     

The energetic cost of locomotion: humans and primates compared to generalized endotherms

A wide range of selective pressures have been advanced as possible causes for the adoption of bipedalism in the hominin lineage. One suggestion has been that because modern human walking is relatively efficient compared to that of a typical quadruped, the ancestral quadruped may have reaped an energetic advantage when it walked on two legs. While it has become clear that human walking is relatively efficient and human running inefficient compared to "generalized endotherms", workers differ in their opinion of how the cost of human bipedal locomotion compares to that of a generalized primate walking quadrupedally. One view is that human walking is particularly efficient in comparison to other primates. The present study addresses this by comparing the cost of human walking and running to that of the eight primate species for which data are available and by comparing cost in primates to that of a "generalized endotherm". There is no evidence that primate locomotion is more costly than that of a generalized endotherm, although more data on adult Old World monkeys and apes would be useful. Further, human locomotion does not appear to be particularly efficient relative to that of other primates.     

Rethinking Primate Origins Again

In 1974, Cartmill introduced the theory that the earliest primate adaptations were related to their being visually oriented predators active on slender branches. Given more recent data on primate‐like marsupials, nocturnal prosimians, and early fossil primates, and the context in which these primates first appeared, this theory has been modified. We hypothesize that our earliest primate relatives were likely exploiting the products of co‐evolving angiosperms, along with insects attracted to fruits and flowers, in the slender supports of the terminal branch milieu. This has been referred to as the primate/angiosperm co‐evolution theory. Cartmill subsequently posited that: “If the first euprimates had grasping feet and blunt teeth adapted for eating fruit, but retained small divergent orbits…” then the angiosperm coevolution theory would have support. The recent discovery of Carpolestes simpsoni provides this support. In addition, new field data on small primate diets, and a new theory concerning the visual adaptations of primates, have provided further evidence supporting the angiosperm coevolution theory.Am. J. Primatol. 75:95‐106, 2013. © 2012 Wiley Periodicals, Inc.     

The Fayum primate forest: Did it exist?

The primates have the reputation of being essentially arboreal, forest-adapted animals. Yet there are many genera and species that inhabit an extremely wide array of non-forest habitats. Nevertheless, palaeoprimatologists often tend to depict fossil primate habitats as being more arboreal and more forest-like than is justified by the facts. It is worthwhile, therefore, to reconsider some current interpretations. In this paper, evidence of the Fayum Oligocene primate deposits are reviewed and discussed. The following conclusions emerge:(1) The large number of primate species indicates that the Fayum ecosystem was an optimum or near-optimum habitat for primates. (2) The lithological characteristics point to a sahélien type of climate. (3) The calcified and silicified root systems, having diameters up to 4 cm, suggest a sahélien type of shrub, bushland and/or small-tree vegetation. (4) The large fossilized logs cannot have grown on the spot and apparently represent driftwood from a more humid climatic belt in the south, as is indicated by damage resulting from fluvial transportation and by palaeobotanical data. (5) There may have been some minor patches or strips of medium-height forests and/or wood-lands in the Fayum delta, but there is no evidence of these.Thus the tall forest in which the earliest known African primates are currently supposed to have lived probably never existed. Grounds for this conclusion were presented by Unger 121 years ago, by Beadnell 75 years ago and by Kräusel 41 years ago, but sank into oblivion. The classic image of the primates as arboreal specialists seems to have interfered with seeing the facts. However, more extensive verification of the evidence by means of palaeobotanical research is still required. The fossil material to do so is readily available.     

Ecogeographic size variation in small-bodied subfossil primates from Ankilitelo, southwestern Madagascar

Variation in body size is well documented for both extant and extinct Malagasy primates, and appears to be correlated with geographic patterns of resource seasonality. Less attention has been paid to extant lemurs in subfossil collections, although it has been suggested that subfossil forms of extant species are characterized by greater size than their modern counterpart. This trend of phyletic size change has been related to climate change, habitat fragmentation, or human hunting. However, space- and time-averaging in the subfossil samples of previous studies may have obscured more general ecogeographic patterns underlying these size differences. Our objective is to examine size variation in subfossil still-extant primates within a regional comparative context to determine if subfossil and living forms conform to similar ecogeographic patterns. We report on the subfossil still-extant primate assemblage from Ankilitelo, southwestern Madagascar (approximately 500 yr BP) to test this hypothesis. The Ankilitelo primates were compared with museum specimens of known locality. Extant taxa were assigned to one of five distinct ecogeographic regions, including spiny thicket, dry deciduous forest, succulent woodland, lowland and subhumid rainforest. Comparisons of tooth size in extant lemurs reveal significant geographical patterns of variation within genera. In general, the primates from Ankilitelo are indeed larger than their modern counterpart. However, these differences fit an ecoregional model of size variation, whereby Ankilitelo species are comparable in size to living forms inhabiting ecoregions present near the cave today. This suggests that Malagasy primates have been subjected to similar patterns of resource seasonality for at least 500 years.     

Bioenergetic Constraints on Primate Abundance

Explaining variation in primate population densities is central to understanding primate ecology, evolution, and conservation. Yet no researchers to date have successfully explained variation in primate population density across dietary class and phylogeny. Most previous work has focused on measures of food availability, as access to food energy likely constrains the number of individuals supported in a given area. However, energy output may provide a measure of energy constraints on population density that does not require detailed data on food availability for a given taxon. Across mammals, many studies have shown that population densities generally scale with body mass^−0.75. Because individual energy expenditures scale with body mass^0.75, population energy use (the product of population density and individual energy use) does not change with body mass, which suggests the existence of energy constraints on population density across body sizes, i.e., taxa are limited to a given amount of energy use, constraining larger taxa to lower densities. We examined population energy use and individual energy expenditure in primates and tested this energy equivalence across body mass. We also used a residual analysis to remove the effects of body mass on primate population densities and energy expenditures using basal metabolic rates (BMR; kcal/d) as a proxy for total daily energy expenditure. After taking into account phylogeny, population energy use did not significantly correlate with body mass. Larger primates, which use more energy per day, live at lower population densities than smaller primates. In addition, we found a significant negative correlation between residuals of BMR from body mass and residuals of population density from body mass after taking phylogeny into account. Thus, energy costs constrain population density across a diverse sample of primates at a given body mass, and primate species that have relatively low BMRs exist at relatively high densities. A better understanding of the determinants of primate energy costs across geography and phylogeny will ultimately help us explain and predict primate population densities.     

Primates got personality,too: Toward an integrative primatology of consistent individual differences in behavior

In recent years, research on animal personality has exploded within the field of behavioral ecology. Consistent individual differences in behavior exist in a wide range of species, and these differences can have fitness consequences and influence several aspects of a species' ecology. In comparison to studies of other animals, however, there has been relatively little research on the behavioral ecology of primate personality. This is surprising given the large body of research within psychology and biomedicine showing that primate personality traits are heritable and linked to health and life history outcomes. In this article, I bring together theoretical perspectives on the ecology and evolution of animal personality with an integrative review of what we know about primate personality from studies conducted on captive, free‐ranging, and wild primates. Incorporating frameworks that emphasize consistency in behavior into primate behavioral ecology research holds promise for improving our understanding of primate behavioral evolution.