Chimpanzee photo11/22/2023 Comparative studies in apes must therefore rely on opportunistic collection of post-mortem tissues. While in vivo studies are permitted in some primates, ethical considerations forcefully apply to studies of apes, particularly to studies involving chimpanzees - our closest extant evolutionary relatives. įor obvious ethical and practical reasons, only a small number of tissue types can be accessed from live humans, and direct experimentation in vivo is impossible. Yet, more than two decades after the first genome-scale comparison of gene expression in humans and chimpanzees, comparative genomic data from apes remains limited to just a handful of tissue types. Comparative genomic studies are not typically hypothesis-driven rather, they aim to build comprehensive comparative catalogs that can be used to infer function, explore the evolution of different regulatory mechanisms, and establish hypotheses based on causal inference between genotypes and phenotypes. One goal of comparative genomic studies in primates has been to characterize gene regulatory variation across a wide range of tissue types. The inference of fitness-related molecular function is profoundly important, not only to studies that attempt to understand the mechanisms of evolutionary change, but also to studies of the genetic and gene regulatory basis for complex traits and diseases in humans. Such patterns suggest functional importance and point to regulatory phenotypes that may affect fitness. Comparative inter-species studies also allow us to identify patterns of regulatory variation that are consistent with the action of natural selection. In particular, studies of gene expression in humans and other apes allow us to identify regulatory changes that may be associated with human-specific adaptations. Here, we present the most comprehensive dataset of comparative gene expression from humans and chimpanzees to date, including a catalog of regulatory mechanisms associated with inter-species differences.Ĭomparative functional genomic studies in primates reveal insight into the evolution of gene regulation and help us identify genes and pathways that are associated with species-specific traits. Using the cis/ trans inference and an analysis of transcription factor binding sites, we identify dozens of transcription factors whose inter-species differences in expression are affecting expression differences between humans and chimpanzees in hundreds of target genes. Using embryoid bodies from a human-chimpanzee fused cell line, we also infer the proportion of inter-species regulatory differences due to changes in cis and trans elements between the species. ![]() ![]() We find hundreds of genes whose regulation is conserved across cell types, as well as genes whose regulation likely evolves under directional selection in one or a handful of cell types. Here, we used single-cell RNA sequencing of embryoid bodies to collect transcriptomic data from over 70 cell types in three humans and three chimpanzees. Comparative gene expression studies in apes are fundamentally limited by the challenges associated with sampling across different tissues.
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