Project description:Understanding the evolutionary mechanisms underlying expansion and reorganization of the human brain is essential to comprehend the emergence of the cognitive abilities typical of our species. Comparative analyses of neuronal phenotypes in closely related species (Homo sapiens; human, Pan troglodytes; chimpanzees and Pan paniscus; bonobos) can shed light onto neuronal changes occurring during evolution, the timing of their appearance and the role of evolutionary mechanisms favoring a particular type of cortical organization in humans. The availability of post-mortem brains of endangered primates is limited and often does not represent important species-specific developmental hallmarks. We used induced pluripotent stem cell (iPSC) technology to model neural progenitor cell migration in Homo and Pan and early development of cortical pyramidal neurons in humans and chimpanzees after following cells grafted in vivo. We present results suggesting differential migration patterns in human neural progenitor cells compared to those of chimpanzees and bonobos in vitro and in vivo. Additionally, we reveal morphometric and functional differences that are suggestive of heterochronic changes in developing human neurons compared to chimpanzees. This report provides a comprehensive analysis of comparative neural development in closely related hominids. The strategy proposed here lays the groundwork for further comparative analysis between human and non-human primates and opens new avenues for understanding the differences in the neural underpinnings of cognition and neurological disease susceptibility between species.
Project description:Comparative analyses of neuronal phenotypes in closely related species can shed light on neuronal changes occurring during evolution. The study of post-mortem brains of nonhuman primates (NHPs) has been limited and often does not recapitulate important species-specific developmental hallmarks. We utilize induced pluripotent stem cell (iPSC) technology to investigate the development of cortical pyramidal neurons following migration and maturation of cells grafted in the developing mouse cortex. Our results show differential migration patterns in human neural progenitor cells compared to those of chimpanzees and bonobos both in vitro and in vivo, suggesting heterochronic changes in human neurons. The strategy proposed here lays the groundwork for further comparative analyses between humans and NHPs and opens new avenues for understanding the differences in the neural underpinnings of cognition and neurological disease susceptibility between species.
Project description:RNA-Seq from lymphoblastoid cell lines for Gorilla, chimpanzee and bonobo species. This RNA-Seq data has been described in the following article: Scally et al., Nature 2012;483;7388;169-75, DOI: 10.1038/nature10842, and its further analysis can be freely submitted for publication. For information on the proper use of data shared by the Wellcome Trust Sanger Institute (including information on acknowledgement), please see http://www.sanger.ac.uk/datasharing/>
Project description:Data from bonobo fibroblast cell lines described in Genome Research paper "Comparative analysis of gene expression patterns in human and African great ape cultured fibroblasts" Keywords = African Great Ape, Human Evolution, Fibroblast, Bonobo, Gorilla, Human Keywords: ordered
Project description:Single-nucleus RNA sequencing (snRNA-seq) was used to profile the transcriptome of 9,887 nuclei in bonobo adult testis. This dataset includes two samples from two different individuals. This dataset is part of a larger evolutionary study of adult testis at the single-nucleus level (97,521 single-nuclei in total) across mammals including 10 representatives of the three main mammalian lineages: human, chimpanzee, bonobo, gorilla, gibbon, rhesus macaque, marmoset, mouse (placental mammals); grey short-tailed opossum (marsupials); and platypus (egg-laying monotremes). Corresponding data were generated for a bird (red junglefowl, the progenitor of domestic chicken), to be used as an evolutionary outgroup.
Project description:Human accelerated regions (HARs) are evolutionarily conserved sequences that acquired human-specific nucleotide changes and reside in genomic regions associated with unique human traits and disease. The majority of HARs (96%) are noncoding, a few of which have been shown to be functional enhancers. Here, we comprehensively tested human and chimpanzee sequences of HARs (N=714) for enhancer activity using a lentivirus-based massively parallel reporter assay (lentiMPRA) in human and chimpanzee iPSC derived neural progenitors at two differentiation time points. We found that 43% (306/714) function as enhancers and over two-thirds (204/306) showed consistent differences in activity between human and chimpanzee sequences across conditions. We also tested all possible permutations of substitutions in seven HARs and found significant positive and negative interactions. Our study provides a comprehensive resource of functional neurodevelopmental HAR enhancers and shows that multiple interacting sites drive evolutionary activity differences.
Project description:Single-nucleus RNA sequencing (snRNA-seq) was used to profile the transcriptome of 12,352 nuclei in chimpanzee adult testis. This dataset includes three samples from three different individuals. This dataset is part of a larger evolutionary study of adult testis at the single-nucleus level (97,521 single-nuclei in total) across mammals including 10 representatives of the three main mammalian lineages: human, chimpanzee, bonobo, gorilla, gibbon, rhesus macaque, marmoset, mouse (placental mammals); grey short-tailed opossum (marsupials); and platypus (egg-laying monotremes). Corresponding data were generated for a bird (red junglefowl, the progenitor of domestic chicken), to be used as an evolutionary outgroup.