Philip L. Reno

Human-specific loss of regulatory DNA and the evolution of human-specific traits

Humans differ from other animals in many aspects of anatomy, physiology, and behaviour; however, the genotypic basis of most human-specific traits remains unknown. Recent whole-genome comparisons have made it possible to identify genes with elevated rates of amino acid change or divergent expression in humans, and non-coding sequences with accelerated base pair changes. Regulatory alterations may be particularly likely to produce phenotypic effects while preserving viability, and are known to underlie interesting evolutionary differences in other species. Here we identify molecular events particularly likely to produce significant regulatory changes in humans: complete deletion of sequences otherwise highly conserved between chimpanzees and other mammals. We confirm 510 such deletions in humans, which fall almost exclusively in non-coding regions and are enriched near genes involved in steroid hormone signalling and neural function. One deletion removes a sensory vibrissae and penile spine enhancer from the human androgen receptor (AR) gene, a molecular change correlated with anatomical loss of androgen-dependent sensory vibrissae and penile spines in the human lineage. Another deletion removes a forebrain subventricular zone enhancer near the tumour suppressor gene growth arrest and DNA-damage-inducible, gamma (GADD45G), a loss correlated with expansion of specific brain regions in humans. Deletions of tissue-specific enhancers may thus accompany both loss and gain traits in the human lineage, and provide specific examples of the kinds of regulatory alterations and inactivation events long proposed to have an important role in human evolutionary divergence.

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.

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.

Adaptationism and the anthropoid postcranium: Selection does not govern the length of the radial neck

The length of the radial neck has been assumed to vary in living and extinct primates in accordance with its role as a moment arm during flexion by the m. biceps brachii. We here use a simple developmental approach to investigate whether or not this trait does, in fact, vary in such a manner. We find, instead, that virtually all variation in radial neck length is explicable as a simple correlate of overall body size, and that there is no evidence to conclude that selection has separately modified radial neck length in response to differing locomotor patterns. Further implications for the interpretation of mammalian skeletal morphology are briefly discussed. J. Morphol. 246:59–67, 2000

Genetic and developmental basis for parallel evolution and its significance for hominoid evolution

Greater understanding of ape comparative anatomy and evolutionary history has brought a general appreciation that the hominoid radiation is characterized by substantial homoplasy.1–4 However, little consensus has been reached regarding which features result from repeated evolution. This has important implications for reconstructing ancestral states throughout hominoid evolution, including the nature of the Pan‐Homo last common ancestor (LCA). Advances from evolutionary developmental biology (evo‐devo) have expanded the diversity of model organisms available for uncovering the morphogenetic mechanisms underlying instances of repeated phenotypic change. Of particular relevance to hominoids are data from adaptive radiations of birds, fish, and even flies demonstrating that parallel phenotypic changes often use similar genetic and developmental mechanisms. The frequent reuse of a limited set of genes and pathways underlying phenotypic homoplasy suggests that the conserved nature of the genetic and developmental architecture of animals can influence evolutionary outcomes. Such biases are particularly likely to be shared by closely related taxa that reside in similar ecological niches and face common selective pressures. Consideration of these developmental and ecological factors provides a strong theoretical justification for the substantial homoplasy observed in the evolution of complex characters and the remarkable parallel similarities that can occur in closely related taxa. Thus, as in other branches of the hominoid radiation, repeated phenotypic evolution within African apes is also a distinct possibility. If so, the availability of complete genomes for each of the hominoid genera makes them another model to explore the genetic basis of repeated evolution.

Metapodial or phalanx? An evolutionary and developmental perspective on the homology of the first ray's proximal segment.

The first mammalian metapodial (MP1) has periodically been argued to actually be a phalanx, because the first ray has one less element than the four posterior rays, and because the MP1 growth plate is proximal like those of all phalanges, rather than distal as in metapodials 2-5. However, growth plates are formed at both ends in non-therian tetrapod metapodials, and phylogenetic analysis demonstrates that growth plate loss is a therian synapomorphy that postdates the establishment of the mammalian phalangeal formula. These data, along with results of developmental and morphological studies, suggest that the MP1 is not a phalanx. The singular, proximal growth plates in MPs 2-5 are likely to be an adaptation to dynamic erect quadrupedal gait which was characterized by conversion of the posterior metapodials into rigid struts with the carpus/tarsus. While the adaptive significance of the reversed ossification of MP1 is less clear, we present three functional/developmental hypotheses.

First steps of bipedality in hominids: evidence from the atelid and proconsulid pelvis

Upright walking absent a bent-hip-bent-knee gait requires lumbar lordosis, a ubiquitous feature in all hominids for which it can be observed. Its first appearance is therefore a central problem in human evolution. Atelids, which use the tail during suspension, exhibit demonstrable lordosis and can achieve full extension of their hind limbs during terrestrial upright stance. Although obviously homoplastic with hominids, the pelvic mechanisms facilitating lordosis appear largely similar in both taxa with respect to abbreviation of upper iliac height coupled with broad sacral alae. Both provide spatial separation of the most caudal lumbar(s) from the iliac blades. A broad sacrum is therefore a likely facet of earliest hominid bipedality. All tailed monkeys have broad alae. By contrast all extant apes have very narrow sacra, which promote “trapping” of their most caudal lumbars to achieve lower trunk rigidity during suspension. The alae in the tailless proconsul Ekembo nyanzae appear to have been quite broad, a character state that may have been primitive in Miocene hominoids not yet adapted to suspension and, by extension, exaptive for earliest bipedality in the hominid/panid last common ancestor. This hypothesis receives strong support from other anatomical systems preserved in Ardipithecus ramidus.

A Penile Spine/Vibrissa Enhancer Sequence Is Missing in Modern and Extinct Humans but Is Retained in Multiple Primates with Penile Spines and Sensory Vibrissae

Previous studies show that humans have a large genomic deletion downstream of the Androgen Receptor gene that eliminates an ancestral mammalian regulatory enhancer that drives expression in developing penile spines and sensory vibrissae. Here we use a combination of large-scale sequence analysis and PCR amplification to demonstrate that the penile spine/vibrissa enhancer is missing in all humans surveyed and in the Neandertal and Denisovan genomes, but is present in DNA samples of chimpanzees and bonobos, as well as in multiple other great apes and primates that maintain some form of penile integumentary appendage and facial vibrissae. These results further strengthen the association between the presence of the penile spine/vibrissa enhancer and the presence of penile spines and macro- or micro- vibrissae in non-human primates as well as show that loss of the enhancer is both a distinctive and characteristic feature of the human lineage.

The Role of Hox in Pisiform and Calcaneus Growth Plate Formation and the Nature of the Zeugopod/Autopod Boundary.

The mesopodium forms at the boundary between the zeugopod and autopod and is composed of short nodular bones that typically lack growth plates. Hoxa11 and Hoxa13 are expressed in mutually exclusive proximal-distal domains that demarcate the zeugopod/autopod boundary. Similarly, Hoxd genes are deployed in two distinct phases during limb development. The early phase corresponds to proximal segments including the zeugopod, and a late phase occurs in the digits. This arrangement produces a gap of low Hoxd expression that is traditionally viewed to correspond to the mesopodium. In contrast to the other mesopodials, the mammalian pisiform and calcaneus form true growth plates. We show that these bones, along with other proximal mesopodials, develop within the Hoxa11 and Hoxd11 expression domains. We also observe that the pisiform growth plate becomes disorganized with Hoxa11 or Hoxd11 loss of function, indicating a direct role for Hox11 in its development. Hoxa13 loss of function has minimal effect on the pisiform and proximal calcaneus as these bones still form secondary centers and undergo longitudinal growth. Consideration of the phenotypes resulting from hypodactyly (Hd) and synpolydactyly homolog (spdh) mutations, which result from altered HOXA13 and HOXD13 proteins, respectively, confirms that Hox13 plays a limited role in the development of the pisiform and calcaneus and suggests that they lie within the early phase of Hox expression. Therefore, with respect to patterns of ossification and gene expression, these bones share much more in common with the zeugopod than the autopod. Such an interpretation fits with the timing of autopod origins during tetrapod evolution.