Gene expression variability in human and chimpanzee populations share common determinants

Abstract

Inter-individual variation in gene expression has been shown to be heritable and is often associated with differences in disease susceptibility between individuals. Many studies focused on mapping associations between genetic and gene regulatory variation, yet much less attention has been paid to the evolutionary processes that shape the observed differences in gene regulation between individuals in humans or any other primate. To begin addressing this gap, we performed a comparative analysis of gene expression variability and expression quantitative trait loci (eQTLs) in humans and chimpanzees, using gene expression data from primary heart samples. We found that expression variability in both species is often determined by non-genetic sources, such as cell-type heterogeneity. However, we also provide evidence that inter-individual variation in gene regulation can be genetically controlled, and that the degree of such variability is generally conserved in humans and chimpanzees. In particular, we found a significant overlap of orthologous genes associated with eQTLs in both species. We conclude that gene expression variability in humans and chimpanzees often evolves under similar evolutionary pressures.

Genetic diversity in chimpanzee transcriptomics does not represent wild populations

“…Thus we filtered our data to a final set of 135 genetically unique individuals (see methods), and computed pairwise identity-by-descent (IBD) metrics for these individuals. We first analysed only the 38 samples from S31, which contains 8 known pairs of first-degree (all parent/offspring) relatives [28]. All 8 of the known pairs had IDB Z1 > 0.60, and 7 had IBD Z1 > 0.70.…”

“…As half of these samples are derived from the National Chimpanzee Brain Resource at George Washington University, a post mortem brain bank, it is likely that these studies are repeatedly sequencing the same brain sample. Similarly, of the 60 heart/muscle samples, 40 have been used more than once, 17 only for heart/muscle purposes - all 17 have been used by both S31 [28] and S28 [31], which were conducted by the same research group using partly overlapping collections of individuals/cell lines. This finding has implications about how much unique transcriptomic information is actually available.…”

Genetic Diversity in Chimpanzee Transcriptomics Does Not Represent Wild Populations

“…Using these values as a guide, we took advantage of known relationships in our data set to define thresholds specific to our data. We first analyzed only the 38 samples from S31, which contains eight known pairs of first-degree (all parent/offspring) relatives ( Fair et al 2020 ). All eight of the known pairs had IDB Z1 > 0.60, and seven had IBD Z1 > 0.70.…”

“…As half of these samples are derived from the National Chimpanzee Brain Resource at George Washington University, a post-mortem brain bank, it is likely that these studies are repeatedly sequencing the same brain sample. Similarly, of the 60 heart/muscle samples, 40 have been used more than once, 17 only for heart/muscle purposes—all 17 have been used by both S31 ( Fair et al 2020 ) and S28 ( Pavlovic et al 2018 ), which were conducted by the same research group using partly overlapping collections of individuals/cell lines. This finding has implications about how much unique transcriptomic information is actually available.…”

“…However, multiple lines of evidence argue that poor sampling is likely to lead to incomplete inferences. Although they had modest sample sizes and featured primarily individuals of Western ancestry, the two largest studies of gene expression in chimpanzees, Pavlovic et al (2018) and Fair et al (2020) , have both shown that inter-individual differences in gene expression have a clear genetic component in both humans and chimpanzees. In parallel, genomic studies of all four chimpanzee subspecies have identified multiple highly differentiated loci that show strong evidence of hard adaptive sweeps in response to the local environment, especially in immune-associated genes in Eastern chimpanzees ( Schmidt et al 2019 ), which are the worst represented in our data.…”