Early hominids may have been weed species.

Panid, gorillid, and hominid social structures appear to have diverged as dramatically as did their locomotor patterns as they emerged from a late Miocene last common ancestor (LCA). Despite their elimination of the sectorial canine complex and adoption of bipedality with its attendant removal of their ready access to the arboreal canopy, Australopithecus was able to easily invade novel habitats after florescence from its likely ancestral genus, Ardipithecus sp. Other hominoids, unable to sustain sufficient population growth, began an inexorable decline, culminating in their restriction to modern refugia. Success similar to that of earliest hominids also characterizes several species of macaques, often termed "weed species." We here review their most salient demographic features and find that a key element is irregularly elevated female survival. It is reasonable to conclude that a similar feature characterized early hominids, most likely made possible by the adoption of social monogamy. Reduced female mortality is a more probable key to early hominid success than a reduction in birth space, which would have been physiologically more difficult.

Automated Isoform Diversity Detector (AIDD): a pipeline for investigating transcriptome diversity of RNA-seq data.

BACKGROUND: As the number of RNA-seq datasets that become available to explore transcriptome diversity increases, so does the need for easy-to-use comprehensive computational workflows. Many available tools facilitate analyses of one of the two major mechanisms of transcriptome diversity, namely, differential expression of isoforms due to alternative splicing, while the second major mechanism-RNA editing due to post-transcriptional changes of individual nucleotides-remains under-appreciated. Both these mechanisms play an essential role in physiological and diseases processes, including cancer and neurological disorders. However, elucidation of RNA editing events at transcriptome-wide level requires increasingly complex computational tools, in turn resulting in a steep entrance barrier for labs who are interested in high-throughput variant calling applications on a large scale but lack the manpower and/or computational expertise. RESULTS: Here we present an easy-to-use, fully automated, computational pipeline (Automated Isoform Diversity Detector, AIDD) that contains open source tools for various tasks needed to map transcriptome diversity, including RNA editing events. To facilitate reproducibility and avoid system dependencies, the pipeline is contained within a pre-configured VirtualBox environment. The analytical tasks and format conversions are accomplished via a set of automated scripts that enable the user to go from a set of raw data, such as fastq files, to publication-ready results and figures in one step. A publicly available dataset of Zika virus-infected neural progenitor cells is used to illustrate AIDD's capabilities. CONCLUSIONS: AIDD pipeline offers a user-friendly interface for comprehensive and reproducible RNA-seq analyses. Among unique features of AIDD are its ability to infer RNA editing patterns, including ADAR editing, and inclusion of Guttman scale patterns for time series analysis of such editing landscapes. AIDD-based results show importance of diversity of ADAR isoforms, key RNA editing enzymes linked with the innate immune system and viral infections. These findings offer insights into the potential role of ADAR editing dysregulation in the disease mechanisms, including those of congenital Zika syndrome. Because of its automated all-inclusive features, AIDD pipeline enables even a novice user to easily explore common mechanisms of transcriptome diversity, including RNA editing landscapes.

Locomotor pattern fails to predict foramen magnum angle in rodents, strepsirrhine primates, and marsupials.

Foramen magnum position has traditionally been used as an indicator of bipedality because it has been thought to favor a more "balanced" skull position. Here, we analyzed foramen magnum angle (FMA) in relation to locomotion in three mammalian orders that include bipedal or orthograde species in addition to quadrupedal or pronograde species. In marsupials and strepsirrhine primates, we found that there is no relationship between locomotor pattern and FMA. In rodents, we found that there is a significant difference in FMA between bipedal and quadrupedal rodents. However, when these species are analyzed in the context of enlarged auditory bullae, this relationship is no longer significant. Additionally, we find a significant relationship between relative brain size and FMA in strepsirrhine primates. Taken together, these data indicate that several developmental modules of the cranium influence FMA, but that locomotion does not. We caution that basicranial evolution is a complex phenomenon that must be explored in the context of each taxon's unique evolutionary and developmental history.

Age, adrenal steroids, and cognitive functioning in captive chimpanzees (Pan troglodytes).

Background: Dehydroepiandrosterone-sulfate is the most abundant circulating androgen in humans and other catarrhines. It is involved in several biological functions, such as testosterone production, glucocorticoid antagonist actions, neurogenesis and neuroplasticty. Although the role of dehydroepiandrosterone-sulfate (DHEAS) in cognition remains elusive, the DHEAS/cortisol ratio has been positively associated with a slower cognitive age-decline and improved mood in humans. Whether this relationship is found in nonhuman primates remains unknown. Methods: We measured DHEAS and cortisol levels in serum of 107 adult chimpanzees to investigate the relationship between DHEAS levels and age. A subset of 21 chimpanzees was used to test the potential associations between DHEAS, cortisol, and DHEAS/cortisol ratio in cognitive function, taking into account age, sex, and their interactions. We tested for cognitive function using the primate cognitive test battery (PCTB) and principal component analyses to categorize cognition into three components: spatial relationship tasks, tool use and social communication tasks, and auditory-visual sensory perception tasks. Results: DHEAS levels, but not the DHEAS/cortisol ratio, declined with age in chimpanzees. Our analyses for spatial relationships tasks revealed a significant, positive correlation with the DHEAS/cortisol ratio. Tool use and social communication had a negative relationship with age. Our data show that the DHEAS/cortisol ratio, but not DHEAS individually, is a promising predictor of spatial cognition in chimpanzees.

Upright walking has driven unique vascular specialization of the hominin ilium.

BACKGROUND: A novel physis in hominins modulates broadening and shortening of the ilium. We report analysis of a vascular canal system whose origin may be associated with this physis and which appears to be also unique to hominins. Its presence is potentially identifiable in the fossil record by its association with a highly enlarged foramen that is consistently present in modern humans and hominin fossils. METHODS: We measured the diameter of this foramen in humans, fossil hominins, and African great apes and corrected for body size. RESULTS: The mean relative human foramen diameter is significantly greater than those of either Pan or Gorilla. Moreover, eight of the nine values of the Cohen's d for these differences in ratios are highly significant and support the ordering of magnitudes: Pan < Gorilla < Homo. The relative foramen diameter of A.L. 288-1 is above the 75th percentile of all other hominoids and at the high end of humans. The foramen is also present in ARA-VP-6/500. CONCLUSIONS: We posit that the presence and significant enlargement of this foramen in fossils can reasonably serve as an indicator that its anterior inferior iliac spine emerged via the unique hominin physis. The foramen can therefore serve as an indicator of hominin iliac ontogenetic specialization for bipedality in fossil taxa.

The vertebral formula of the last common ancestor of African apes and humans.

The modal number of lumbar vertebrae in modern humans is five. It varies between three and four in extant African apes (mean=3.5). Because both chimpanzees (Pan troglodytes) and gorillas (Gorilla gorilla) possess the same distributions of thoracic, lumbar, and sacral vertebrae, it has been assumed from parsimony that the last common ancestor (LCA) of African apes and humans possessed a similarly short lower back. This "short-backed LCA" scenario has recently been viewed favorably in an analysis of the intra- and interspecific variation in axial formulas observed among African apes and humans (Pilbeam, 2004. J Exp Zool 302B:241-267). However, the number of bonobo (Pan paniscus) specimens in that study was small (N=17). Here we reconsider vertebral type and number in the LCA in light of an expanded P. paniscus sample as well as evidence provided by the human fossil record. The precaudal (pre-coccygeal) axial column of bonobos differs from those of chimpanzees and gorillas in displaying one additional vertebra as well as significantly different combinations of sacral, lumbar, and thoracic vertebrae. These findings, along with the six-segmented lumbar column of early Australopithecus and early Homo, suggest that the LCA possessed a long axial column and long lumbar spine and that reduction in the lumbar column occurred independently in humans and in each ape clade, and continued after separation of the two species of Pan as well. Such an explanation is strongly congruent with additional details of lumbar column reduction and lower back stabilization in African apes.

Neuron loss associated with age but not Alzheimer's disease pathology in the chimpanzee brain.

In the absence of disease, ageing in the human brain is accompanied by mild cognitive dysfunction, gradual volumetric atrophy, a lack of significant cell loss, moderate neuroinflammation, and an increase in the amyloid beta (Aß) and tau proteins. Conversely, pathologic age-related conditions, particularly Alzheimer's disease (AD), result in extensive neocortical and hippocampal atrophy, neuron death, substantial Aß plaque and tau-associated neurofibrillary tangle pathologies, glial activation and severe cognitive decline. Humans are considered uniquely susceptible to neurodegenerative disorders, although recent studies have revealed Aß and tau pathology in non-human primate brains. Here, we investigate the effect of age and AD-like pathology on cell density in a large sample of postmortem chimpanzee brains (n = 28, ages 12-62 years). Using a stereologic, unbiased design, we quantified neuron density, glia density and glia:neuron ratio in the dorsolateral prefrontal cortex, middle temporal gyrus, and CA1 and CA3 hippocampal subfields. Ageing was associated with decreased CA1 and CA3 neuron densities, while AD pathologies were not correlated with changes in neuron or glia densities. Differing from cerebral ageing and AD in humans, these data indicate that chimpanzees exhibit regional neuron loss with ageing but appear protected from the severe cell death found in AD. This article is part of the theme issue 'Evolution of the primate ageing process'.

The exceptional abandonment of metal tools by North American hunter-gatherers, 3000 B.P.

Most prehistoric societies that experimented with copper as a tool raw material eventually abandoned stone as their primary medium for tool making. However, after thousands of years of experimentation with this metal, North American hunter-gatherers abandoned it and returned to the exclusive use of stone. Why? We experimentally confirmed that replica copper tools are inferior to stone ones when each is sourced in the same manner as their archaeological counterparts and subjected to identical tasks. Why, then, did copper consistently lead to more advanced metallurgy in most other areas of the world? We suggest that it was the unusual level of purity in the North American copper sourced by North American groups, and that naturally occurring alloys yielded sufficiently superior tools to encourage entry into the copper-bronze-iron continuum of tool manufacture in other parts of the world.

Cardiac disease is linked to adiposity in male gorillas (Gorilla gorilla gorilla).

Cardiac disease is a major cause of morbidity and mortality for adult gorillas. Previous research indicates a sex-based difference with predominantly males demonstrating evidence of left ventricular hypertrophy. To evaluate these findings, we analyzed serum markers with cardiac measures in a large sample of gorillas. The study sample included 44 male and 25 female gorillas housed at American Association of Zoo and Aquariums (AZA)-accredited zoos. Serum samples were collected from fasted gorillas during routine veterinary health exams and analyzed to measure leptin, adiponectin, IGF-1, insulin, ferritin, glucose, triglycerides, and cholesterol. Cardiac ultrasonography via transthoracic echocardiogram was performed simultaneously. Three echocardiographic parameters were chosen to assess cardiac disease according to parameters established for captive lowland gorillas: left ventricular internal diameter, inter-ventricular septum thickness, and left ventricular posterior wall thickness. Our data revealed that high leptin, low adiponectin, and lowered cholesterol were significantly and positively correlated with measures of heart thickness and age in males but not in females. Lowered cholesterol in this population would be categorized as elevated in humans. High leptin and low adiponectin are indicative of increased adiposity and suggests a potential parallel with human obesity and cardiovascular disease in males. Interestingly, while females exhibited increased adiposity with age, they did not progress to cardiac disease.

Patterns of correlation and covariation of anthropoid distal forelimb segments correspond to Hoxd expression territories.

Anthropoids in general and hominoids in particular exhibit differential adaptations in forearm and digital skeletal proportions to a diverse array of locomotor modes. Hox genes act as selector genes with spatially regulated expression patterns during development. Their expression in the forelimb appears to define modules that specify differential skeletal growth. Here we explore forelimb skeletal proportions in a large sample of anthropoids from a background provided by Hoxd expression patterns in late-stage murine embryonic forelimbs. Interspecific correlation and principal components analyses of primate forelimb data indicate that morphological variation in anthropoids reflects well-defined developmental modules downstream of Hoxd expression. The phalanges of digit one appear to represent a single growth module, whereas the metacarpals and manual phalanges of the posterior digits correspond to a second, independent, expression territory that extends proximally into the distal zeugopod. In particular, hominoids show very high correlations among the posterior digits and the independence of digit one. In addition, the distal radius is generally highly correlated with the posterior digits and not digit one. Relying on established functional differences among Hox paralogs, we present a model that parsimoniously explains hominoid forearm and digital proportions as a consequence of downstream effects of Hox. We, therefore, suggest that Hox-defined developmental modules have served as evolutionary modules during manual evolution in anthropoids.

Ectocranial suture closure in Pan troglodytes and Gorilla gorilla: pattern and phylogeny.

The order in which ectocranial sutures undergo fusion displays species-specific variation among primates. However, the precise relationship between suture closure and phylogenetic affinities is poorly understood. In this study, we used Guttman Scaling to determine if the modal progression of suture closure differs among Homo sapiens, Pan troglodytes, and Gorilla gorilla. Because DNA sequence homologies strongly suggest that P. troglodytes and Homo sapiens share a more recent common ancestor than either does with G. gorilla, we hypothesized that this phylogenetic relationship would be reflected in the suture closure patterns of these three taxa. Results indicated that while all three species do share a similar lateral-anterior closure pattern, G. gorilla exhibits a unique vault pattern, which, unlike humans and P. troglodytes, follows a strong posterior-to-anterior gradient. P. troglodytes is therefore more like Homo sapiens in suture synostosis.

Microglia changes associated to Alzheimer's disease pathology in aged chimpanzees.

In Alzheimer's disease (AD), the brain's primary immune cells, microglia, become activated and are found in close apposition to amyloid beta (Aß) protein plaques and neurofibrillary tangles (NFT). The present study evaluated microglia density and morphology in a large group of aged chimpanzees (n = 20, ages 37-62 years) with varying degrees of AD-like pathology. Using immunohistochemical and stereological techniques, we quantified the density of activated microglia and morphological variants (ramified, intermediate, and amoeboid) in postmortem chimpanzee brain samples from prefrontal cortex, middle temporal gyrus, and hippocampus, areas that show a high degree of AD pathology in humans. Microglia measurements were compared to pathological markers of AD in these cases. Activated microglia were consistently present across brain areas. In the hippocampus, CA3 displayed a higher density than CA1. Aß42 plaque volume was positively correlated with higher microglial activation and with an intermediate morphology in the hippocampus. Aß42-positive vessel volume was associated with increased hippocampal microglial activation. Activated microglia density and morphology were not associated with age, sex, pretangle density, NFT density, or tau neuritic cluster density. Aged chimpanzees displayed comparable patterns of activated microglia phenotypes as well as an association of increased microglial activation and morphological changes with Aß deposition similar to AD patients. In contrast to human AD brains, activated microglia density was not significantly correlated with tau lesions. This evidence suggests that the chimpanzee brain may be relatively preserved during normal aging processes but not entirely protected from neurodegeneration as previously assumed.

Aged chimpanzees exhibit pathologic hallmarks of Alzheimer's disease.

Alzheimer's disease (AD) is a uniquely human brain disorder characterized by the accumulation of amyloid-beta protein (Aß) into extracellular plaques, neurofibrillary tangles (NFT) made from intracellular, abnormally phosphorylated tau, and selective neuronal loss. We analyzed a large group of aged chimpanzees (n = 20, age 37-62 years) for evidence of Aß and tau lesions in brain regions affected by AD in humans. Aß was observed in plaques and blood vessels, and tau lesions were found in the form of pretangles, NFT, and tau-immunoreactive neuritic clusters. Aß deposition was higher in vessels than in plaques and correlated with increases in tau lesions, suggesting that amyloid build-up in the brain's microvasculature precedes plaque formation in chimpanzees. Age was correlated to greater volumes of Aß plaques and vessels. Tangle pathology was observed in individuals that exhibited plaques and moderate or severe cerebral amyloid angiopathy, a condition in which amyloid accumulates in the brain's vasculature. Amyloid and tau pathology in aged chimpanzees suggests these AD lesions are not specific to the human brain.

Histomorphological and geometric properties of human femoral cortex in individuals over 50: Implications for histomorphological determination of age-at-death.

Cortical area, area moment of inertia, and polar moment of inertia were determined from the midshafts of a series of 62 femurs (34 female and 28 male) from a U. S. white population, ages 51-95. The density of osteons and osteon fragments (per mm2 ) was also determined. Neither osteon nor osteon fragment density was significantly correlated with age. These variables were correlated, however, with normalized cortical and endosteal areas, normalized area moment of inertia, and polar moment of inertia. Osteon fragment numbers alone are not highly correlated with cross-sectional properties. This research suggests that osteon density and osteon fragment density are significantly related to cortical mass and distribution in older people, but are not a direct function of age in persons over 50 years of age. Histological age estimates in older individuals must, therefore, be used with extreme caution. © 1994 Wiley-Liss, Inc.

Humans and great apes share increased neocortical neuropeptide Y innervation compared to other haplorhine primates.

Neuropeptide Y (NPY) plays a role in a variety of basic physiological functions and has also been implicated in regulating cognition, including learning and memory. A decrease in neocortical NPY has been reported for Alzheimer's disease, schizophrenia, bipolar disorder, and depression, potentially contributing to associated cognitive deficits. The goal of the present analysis was to examine variation in neocortical NPY-immunoreactive axon and varicosity density among haplorhine primates (monkeys, apes, and humans). Stereologic methods were used to measure the ratios of NPY-expressing axon length density to total neuron density (ALv/Nv) and NPY-immunoreactive varicosity density to neuron density (Vv/Nv), as well as the mean varicosity spacing in neocortical areas 10, 24, 44, and 22 (Tpt) of humans, African great apes, New World monkeys, and Old World monkeys. Humans and great apes showed increased cortical NPY innervation relative to monkey species for ALv/Nv and Vv/Nv. Furthermore, humans and great apes displayed a conserved pattern of varicosity spacing across cortical areas and layers, with no differences between cortical layers or among cortical areas. These phylogenetic differences may be related to shared life history variables and may reflect specific cognitive abilities.

An enlarged postcranial sample confirms Australopithecus afarensis dimorphism was similar to modern humans.

In a previous study, we introduced the template method as a means of enlarging the Australopithecus afarensis postcranial sample to more accurately estimate its skeletal dimorphism. Results indicated dimorphism to be largely comparable to that of Homo sapiens. Some have since argued that our results were biased by artificial homogeneity in our Au. afarensis sample. Here we report the results from inclusion of 12 additional, newly reported, specimens. The results are consistent with those of our original study and with the hypothesis that early hominid demographic success derived from a reproductive strategy involving male provisioning of pair-bonded females.

Variation in mammalian proximal femoral development: comparative analysis of two distinct ossification patterns.

The developmental anatomy of the proximal femur is complex. In some mammals, including humans, the femoral head and greater trochanter emerge as separate ossification centres within a common chondroepiphysis and remain separate throughout ontogeny. In other species, these secondary centres coalesce within the chondroepiphysis to form a single osseous epiphysis much like the proximal humerus. These differences in femoral ontogeny have not been previously addressed, yet are critical to an understanding of femoral mineralization and architecture across a wide range of mammals and may have key implications for understanding and treating hip abnormalities in humans. We evaluated femora from 70 mammalian species and categorized each according to the presence of a 'separate' or 'coalesced' proximal epiphysis based on visual assessment. We found that ossification type varies widely among mammals: taxa in the 'coalesced' group include marsupials, artiodactyls, perissodactyls, bats, carnivores and several primates, while the 'separate' group includes hominoids, many rodents, tree shrews and several marine species. There was no clear relationship to body size, phylogeny or locomotion, but qualitative and quantitative differences between the groups suggest that ossification type may be primarily an artefact of femoral shape and neck length. As some osseous abnormalities of the human hip appear to mimic the normal morphology of species with coalesced epiphyses, these results may provide insight into the aetiology and treatment of human hip disorders such as femoroacetabular impingement and early-onset osteoarthritis.

Sexual dimorphism in Australopithecus afarensis was similar to that of modern humans.

The substantial fossil record for Australopithecus afarensis includes both an adult partial skeleton [Afar Locality (A.L.) 288-1, "Lucy"] and a large simultaneous death assemblage (A.L. 333). Here we optimize data derived from both to more accurately estimate skeletal size dimorphism. Postcranial ratios derived from A.L. 288-1 enable a significant increase in sample size compared with previous studies. Extensive simulations using modern humans, chimpanzees, and gorillas confirm that this technique is accurate and that skeletal size dimorphism in A. afarensis was most similar to that of contemporary Homo sapiens. These data eliminate some apparent discrepancies between the canine and skeletal size dimorphism in hominoids, imply that the species was not characterized by substantial sexual bimaturation, and greatly increase the probability that the reproductive strategy of A. afarensis was principally monogamy.

The Maka femur and its bearing on the antiquity of human walking: applying contemporary concepts of morphogenesis to the human fossil record.

MAK-VP-1/1, a proximal femur recovered from the Maka Sands (ca. 3.4 mya) of the Middle Awash, Ethiopia, and attributed to Australopithecus afarensis, is described in detail. It represents the oldest skeletal evidence of locomotion in this species, and is analyzed from a morphogenetic perspective. X-ray, CT, and metric data are evaluated, using a variety of methods including discriminant function. The specimen indicates that the hip joint of A. afarensis was remarkably like that of modern humans, and that the dramatic muscle allocation shifts which distinguish living humans and African apes were already present in a highly derived form in this species. Its anatomy provides no indication of any form of locomotion save habitual terrestrial bipedality, which very probably differed only trivially from that of modern humans.