Genetic Diversity in Chimpanzee Transcriptomics Does Not Represent Wild Populations.

Navya Shukla,Irene Gallego Romero,Bobbie Shaban,Selene Fernández Valverde

doi:10.1093/gbe/evab247

Abstract

Chimpanzees (Pan troglodytes) are a genetically diverse species, consisting of four highly distinct subspecies. As humans’ closest living relative, they have been a key model organism in the study of human evolution, and comparisons of human and chimpanzee transcriptomes have been widely used to characterize differences in gene expression levels that could underlie the phenotypic differences between the two species. However, the subspecies from which these transcriptomic data sets have been derived is not recorded in metadata available in the public NCBI Sequence Read Archive (SRA). Furthermore, labeling of RNA sequencing (RNA-seq) samples is for the most part inconsistent across studies, and the true number of individuals from whom transcriptomic data are available is difficult to ascertain. Thus, we have evaluated genetic diversity at the subspecies and individual level in 486 public RNA-seq samples available in the SRA, spanning the vast majority of public chimpanzee transcriptomic data. Using multiple population genetics approaches, we find that nearly all samples (96.6%) have some degree of Western chimpanzee ancestry. At the individual donor level, we identify multiple samples that have been repeatedly analyzed across different studies and identify a total of 135 genetically distinct individuals within our data, a number that falls to 89 when we exclude likely first- and second-degree relatives. Altogether, our results show that current transcriptomic data from chimpanzees are capturing low levels of genetic diversity relative to what exists in wild chimpanzee populations. These findings provide important context to current comparative transcriptomics research involving chimpanzees.

Highlights

Chimpanzees (Pan troglodytes) are one of two extant members of the genus Pan, estimated to have diverged from the ancestral human lineage between 6 and 13 Ma (PradoMartinez et al 2013)
We focused on 3,221 samples sequenced by Illumina HiSeq 2000, 2500, and 4000 to reduce biases in the data caused by different sequencing technologies and instruments
Comparisons with chimpanzees are essential for understanding human evolution and the genetic basis of human-specific traits

Summary

Introduction

Chimpanzees (Pan troglodytes) are one of two extant members of the genus Pan, estimated to have diverged from the ancestral human lineage between 6 and 13 Ma (PradoMartinez et al 2013). Over the last 13 years, RNA sequencing (RNA-seq), a relatively low-cost and high-throughput technology, has emerged as one of the leading approaches in this question, with much work having been done to characterize differences in gene expression patterns across humans, chimpanzees, and other primates (Gallego Romero et al 2012). Transcriptomic studies have compared gene expression across organ systems and provided chimpanzee transcriptomes for various tissues (Brawand et al 2011; Cardoso-Moreira et al 2019; Blake et al 2020), often with a focus on the brain and neural development, to identify the molecular basis of cognitive and behavioral differences (Mostajo-Radji et al 2020). In parallel, induced pluripotent stem cells (iPSCs) from chimpanzees, which can be derived from existing cell lines or donor animals through minimally invasive means, are rapidly becoming established as models to study developmental intermediates and other hard-to-sample tissues (Dannemann and Gallego Romero 2021)

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Results

Conclusion