Accelerated Evolution of Context-Dependent Gene Expression in Primate Immune Cells

Abstract

Regulatory variation is widely recognized as a driver of evolution within and between species, including in the primate lineage. Evidence for potentially adaptive regulatory evolution in primates comes from both sequence-based tests for selection and cross-species comparisons of gene expression. However, comparative studies of gene expression have tended to focus on baseline cellular states, despite growing evidence that context-dependent gene regulation is important. Here, we investigate the evolution of gene expression in lymphoblastoid cell lines (LCLs) from 6 primate lineages (humans, chimpanzees, bonobos, western gorillas, Sumatran orangutans, and rhesus macaques) using data from both control and 5 perturbed cellular conditions (n=22-25 individuals per condition). Analyzing baseline expression data, we find that genes involved in immunity often exhibit lineage-specific transcriptional shifts, and that these genes occur near regions with lineage-specific sequence acceleration and lineage-specific epigenomic states. However, the subset of genes that respond to in vitro perturbations have evolved at significantly higher rates than environmentally-insensitive genes, a finding we replicate in an independent four-species dataset of primary white blood cells (n=26). Together, our findings support the argument that focusing on baseline states alone provides a biased view of gene regulatory evolution, and suggest that studying gene regulation in dynamic contexts can enrich our understanding of primate evolution.

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BibTeX RIS

BibTeX

@misc{durvasula2026accelerated,
  title = {{Accelerated Evolution of Context-Dependent Gene Expression in Primate Immune Cells}},
  author = {A. Durvasula and A. Longtin and A. M. Arner and K. Köhler and I. Rivas-Gonzalez and J. Tung and G. Housman and A. J. Lea},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.23.753790},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.23.753790v1},
  note = {CC BY-NC-ND},
}

RIS

TY  - UNPB
TI  - Accelerated Evolution of Context-Dependent Gene Expression in Primate Immune Cells
AU  - A. Durvasula
AU  - A. Longtin
AU  - A. M. Arner
AU  - K. Köhler
AU  - I. Rivas-Gonzalez
AU  - J. Tung
AU  - G. Housman
AU  - A. J. Lea
PY  - 2026
DA  - 2026/09/23
PB  - bioRxiv
DO  - 10.64898/2026.09.23.753790
UR  - https://www.biorxiv.org/content/10.64898/2026.09.23.753790v1
AB  - Regulatory variation is widely recognized as a driver of evolution within and between species, including in the primate lineage. Evidence for potentially adaptive regulatory evolution in primates comes from both sequence-based tests for selection and cross-species comparisons of gene expression. However, comparative studies of gene expression have tended to focus on baseline cellular states, despite growing evidence that context-dependent gene regulation is important. Here, we investigate the evolution of gene expression in lymphoblastoid cell lines (LCLs) from 6 primate lineages (humans, chimpanzees, bonobos, western gorillas, Sumatran orangutans, and rhesus macaques) using data from both control and 5 perturbed cellular conditions (n=22-25 individuals per condition). Analyzing baseline expression data, we find that genes involved in immunity often exhibit lineage-specific transcriptional shifts, and that these genes occur near regions with lineage-specific sequence acceleration and lineage-specific epigenomic states. However, the subset of genes that respond to in vitro perturbations have evolved at significantly higher rates than environmentally-insensitive genes, a finding we replicate in an independent four-species dataset of primary white blood cells (n=26). Together, our findings support the argument that focusing on baseline states alone provides a biased view of gene regulatory evolution, and suggest that studying gene regulation in dynamic contexts can enrich our understanding of primate evolution.
ER  -

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