Appropriate Assignment of Fossil Calibration Information Minimizes the Difference between Phylogenetic and Pedigree Mutation Rates in Humans.

Studies that measured mutation rates in human populations using pedigrees have reported values that differ significantly from rates estimated from the phylogenetic comparison of humans and chimpanzees. Consequently, exchanges between mutation rate values across different timescales lead to conflicting divergence time estimates. It has been argued that this variation of mutation rate estimates across hominoid evolution is in part caused by incorrect assignment of calibration information to the mean coalescent time among loci, instead of the true genetic isolation (speciation) time between humans and chimpanzees. In this study, we investigated the feasibility of estimating the human pedigree mutation rate using phylogenetic data from the genomes of great apes. We found that, when calibration information was correctly assigned to the human⁻chimpanzee speciation time (and not to the coalescent time), estimates of phylogenetic mutation rates were statistically equivalent to the estimates previously reported using studies of human pedigrees. We conclude that, within the range of biologically realistic ancestral generation times, part of the difference between whole-genome phylogenetic and pedigree mutation rates is due to inappropriate assignment of fossil calibration information to the mean coalescent time instead of the speciation time. Although our results focus on the human⁻chimpanzee divergence, our findings are general, and relevant to the inference of the timescale of the tree of life.

New cranium of the endemic Caribbean platyrrhine, Antillothrix bernensis, from La Altagracia Province, Dominican Republic.

Recent paleontological collection in submerged caves in the eastern Dominican Republic has yielded new specimens of Antillothrix bernensis. Here we describe a complete cranium of an adult individual (MHD 20) and provide phenetic comparisons to other endemic Caribbean taxa and extant mainland platyrrhines using three-dimensional geometric morphometric methods (3DGM). Qualitative and quantitative comparisons support conclusions based on other recently described fossil material: Antillothrix has a dentition lacking clear dietary specialization, an elongated brain case with strong temporal lines, and a vertically oriented nuchal plane. MHD 20 shares a combination of traits with a previously published subadult specimen (MHD 01) including a deep depression at glabella, dorsoventrally elongated orbits, and a relatively large face. This shared morphology reinforces the taxonomic affinity of the two specimens, with differences between the two likely reflecting the younger ontogenetic age of MHD 01. Comparisons to the extant platyrrhines paint a complicated picture as the results of between-group principal components analyses (bgPCA) indicate that Antillothrix does not share a suite of morphological features exclusively with any one genus. Depending on which bgPC axes are visualized, and which subset of landmarks is included (i.e., only those describing the shape of the face/palate for inclusion of Xenothrix), MHD 20 is most similar in shape to the atelids, Alouatta, Lagothrix, and Brachyteles, or an otherwise "empty" region of shape space. It groups neither with Cebus nor Callicebus, two taxa that Antillothrix has been associated with in previous studies based on much less complete material. The Antillothrix cranium does not exhibit any of the derived characters classically used to diagnose or define any single clade; rather its morphology shares features with multiple platyrrhine groups. This is consistent with the interpretation that Antillothrix preserves a primitive morphology, which accords with the hypothesis positing an early arrival of platyrrhines in the Caribbean.

Multispecies coalescent analysis of the early diversification of neotropical primates: phylogenetic inference under strong gene trees/species tree conflict.

Neotropical primates (NP) are presently distributed in the New World from Mexico to northern Argentina, comprising three large families, Cebidae, Atelidae, and Pitheciidae, consequently to their diversification following their separation from Old World anthropoids near the Eocene/Oligocene boundary, some 40 Ma. The evolution of NP has been intensively investigated in the last decade by studies focusing on their phylogeny and timescale. However, despite major efforts, the phylogenetic relationship between these three major clades and the age of their last common ancestor are still controversial because these inferences were based on limited numbers of loci and dating analyses that did not consider the evolutionary variation associated with the distribution of gene trees within the proposed phylogenies. We show, by multispecies coalescent analyses of selected genome segments, spanning along 92,496,904 bp that the early diversification of extant NP was marked by a 2-fold increase of their effective population size and that Atelids and Cebids are more closely related respective to Pitheciids. The molecular phylogeny of NP has been difficult to solve because of population-level phenomena at the early evolution of the lineage. The association of evolutionary variation with the distribution of gene trees within proposed phylogenies is crucial for distinguishing the mean genetic divergence between species (the mean coalescent time between loci) from speciation time. This approach, based on extensive genomic data provided by new generation DNA sequencing, provides more accurate reconstructions of phylogenies and timescales for all organisms.

The effective population sizes of the anthropoid ancestors of the human-chimpanzee lineage provide insights on the historical biogeography of the great apes.

The recent development of methods that apply coalescent theory to phylogenetic problems has enabled the study of the population-level phenomena that drove the diversification of anthropoid primates. Effective population size, Ne, is one of the main parameters that constitute the theoretical underpinning of these new analytical approaches. For this reason, the ancestral N(e) of selected primate lineages has been thoroughly investigated. However, for some of these lineages, the estimates of ancestral N(e) reported in several studies present significant variation. This is the case for the common ancestor of humans and chimpanzees. Moreover, several ancestral anthropoid lineages have been ignored in the studies conducted so far. Because N(e) is fundamental to understand historic species demography, it is a crucial component of a complete description of the historical scenario of primate evolution. It also provides information that is helpful for differentiating between competing biogeographical hypotheses. In this study, the effective population sizes of the anthropoid ancestors of the human-chimp lineage are inferred using data sets of coding and noncoding sequences. A general pattern of a serial decline of population sizes is found between the ancestral lineage of Anthropoidea and that of Homo and Pan. When the theoretical distribution of gene trees was derived from the parametric estimates obtained, it closely corresponded to the empirical frequency of inferred gene trees along the genome. The most abrupt decrease of N(e) was found between the ancestors of all great apes and those of the African great apes alone. This suggests the occurrence of a genetic bottleneck during the evolution of Homininae, which corroborates the origin of African apes from a Eurasian ancestor.

A retrotransposição de mRNAs como fator de variabilidade genética no genoma humano e de outros primatas / The retrotransposition of mRNAs as a factor of genetic variability in the human and other primates genomes

Duplicação genica é uma das principais forças levando a evolução dos genomas eucarioto. O impacto de duplicações gênicas/genômicas vem sendo investigado a muito tempo em humanos e outros primatas. Um segundo mecanismo de duplicação gênica, a retrotransposição baseada em RNA maduros, vem sendo menos estudada devido ao seu potencial menor de gerar cópias funcionais. No entanto, recentemente, publicações descreveram retrocópias funcionais em humanos, roedores e mosca de fruta. Nesta tese, para investigar sobre retrocópias causando variabilidade genética no genoma de primatas, nós desenvolvemos a implementamos os métodos para detectar estas inserções. Utilizando nove genomas e transcriptomas publicamente disponíveis (sete primatas e dois roedores) nós confirmamos um número similar, porém, com origem independente, de retrocópias em primatas e roedores. Nós também encontramos um enriquecimento de retrocópias no genoma de Platyrrhini, possivelmente explicado pela expansão de L1PA7 e L1P3 nestes genomas. Posteriormente, nós analisamos a ortologia de retrocópias no genoma de primatas e encontramos 127 eventos específicos à linhagem humana. Nós também exploramos dados do projeto 1000 Genomes para detectar retrocópias polimórficas (retroCNVs germinativos) e encontramos 17 eventos, presentes no genoma referência humano, mas ausentes em mais de um indivíduo. Similarmente, nós investigamos novas retroduplicações de mRNAs no genoma humano, detectando 21 eventos ausentes do genoma referência. Finalmente, investigamos a existência de retroCNVs somáticos e descrevemos sete possíveis retrocópias somáticas. Apesar de sua possível insignificância, nós encontramos que algumas retrocópias compartilhadas entre todos os primatas, espécie específicas, e polimórficas podem ser expressas per se ou como transcritos quiméricos com genes hospedeiros. Sobretudo, nós encontramos que retrocópias são um fator importante da variabilidade genética inter-espécie, intra-espécie e intra-indivíduo e podem estar influenciando a evolução de mamíferos ao criar reservatórios de duplicações potencialmente funcionais

Gene duplication is a major driving force of evolution in eukaryotic genome. The impact of gene/genomic duplication has long been investigated in human and other primates. A second mechanism of gene duplication, retrotransposition, which is based on mature RNA, has been traditionally less studied due to their lower potential to generate functional copies. Recently, however, publications described functional retrocopies in humans, murines and drosophila. Here, to gain insights of the genetic variability arising from retrocopies on primate genomes, we developed and implemented the methods to detect these insertions. Using nine publicly available reference genomes and transcriptomes (seven primates and two rodents) we described a similar number independently arisen retrocopies in primates and rodents. We also found an enrichment of retrocopies in Platyrhinni genomes, putatively explained by the expansion of L1PA7 and L1P3 in these genomes. Next, we evaluated the orthology of retrocopies in primate genomes and found 127 events specific to human lineage. We also explored 1000 Genomes Project data to detect polymorphic events (germinative retroCNVs) on human populations and found 17 events, present on the reference genome, absent in more than one individual. Conversely, we also investigated new insertions of mRNA retroduplications in the human genome, detecting 21 events absent to the human reference genome. Finally, we evaluated the existence of somatic retroCNVs and described seven putative somatic retrocopies. Despite their putative insignificance, we found that some of these shared, specie-specific and polymorphic events may be expressed per se and as chimeric transcripts within host genes. Taken together, we found that retrocopies are a great factor of genetic variation interspecie, intraspecie e intraindividual and may be affecting mammal evolution by creating reservoirs of potentially functional duplications

SOME EVOLUTIONARY TENDENCIES OF NEOTROPICAL PRIMATES: Algunas tendencias evolutivas de los primates neotropicales

The evolution of neotropical primates has occurred isolated from other primates of the world, resulting in a distinct evolutionary history. Various characteristics of neotropical primates (Platyrrhini) are quite distinct from those of the Old World (Catarrhini), including the dental formula, the position of cranial plates, the anatomy of the auditory apparatus, much less average body weights, much less terrestrial adaptation, prehensile tails for some, and conservative phenotypes. Additionally monogamous forms of platyrrhini share a tendency for rapid chromosome evolution with one monogamous group of catarrhines (Hylobatids or gibbons). The phyletic history of the platyrrhine monkeys seems to contrast with that of the catarrhine inasmuch as there was a very early division (Miocene) of the New World monkeys into groups that exist today, whereas the appearance of Old World primate family groups seemed to have occurred much more recently in the Plio-Pleistocene. Some of these tendencies can be explained hypothetically, looking at ecological characteristics suggested for the new continent while other tendencies are perhaps the result of random evolutionary pathways taken during the course of evolution such as genetic drift and founder effect. Nevertheless there is still much work to be done to be able to recognize the singularities of the Platyrrines and to appreciate the details of their evolution.

La evolución de los primates neotropicales ha transcurrido aislada o de forma independiente a la de otros primates del mundo, porque poseen una historia evolutiva diferente. Hay varias características de los primates neotropicales (Platirrinos) que son bien distintas a las del viejo mundo (Catarrinos), incluyendo la fórmula dental, el arreglo de las placas craneales, la anatomía del aparato auditivo, pesos corporales menores, una menor adaptación a comportamientos terrestres, algunos poseen colas prensiles y baja diferenciación fenotípica. Formas monógamas de platirrinos comparten una tendencia de evolución cromosómica rápida con un grupo monógamo de Catarrinos (los Hilobátidos o gibones). La historia filogenética de platirrinos, contrasta con la de catarrinos debido a una división filética antigua (mioceno) de los primates del nuevo mundo en dos grupos, con características filogenéticas expresadas en las especies actuales. En contraste, la diferenciación de catarrinos con características que se pueden identificar en especies actuales no sucedió sino hasta el Plio-Pleistoceno. Algunas de estas tendencias, pueden ser explicadas hipotéticamente teniendo en cuenta las características ecológicas planteadas en el nuevo continente; otras tendencias tal vez son el resultado de caminos evolutivos tomados al azar durante la evolución del grupo o, como resultado tanto de deriva genética como de un efecto fundador. Sin embargo, queda mucho trabajo para reconocer la totalidad de las singularidades de los platirrinos y poder apreciar los detalles de su evolución.