Positive selection of the trim family regulatory region in primate genomes

Dan Dan He, Yueer Lu, Rachel Gittelman, Yabin Jin, Fei Ling, Akey Joshua

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Viral selection pressure has acted on restriction factors that play an important role in the innate immune system by inhibiting the replication of viruses during primate evolution. Tripartite motif-containing (TRIM) family members are some of these restriction factors. It is becoming increasingly clear that gene expression differences, rather than protein-coding regions changes, could play a vital role in the anti-retroviral immune mechanism. Increasingly, recent studies have created genome-scale catalogues of DNase I hypersensitive sites (DHSs), which demark potentially functional regulatory DNA. To improve our understanding of the molecular evolution mechanism of antiviral differences between species, we leveraged 14 130 DHSs derived from 145 cell types to characterize the regulatory landscape of the TRIM region. Subsequently, we compared the alignments of the DHSs across six primates and found 375 DHSs that are conserved in non-human primates but exhibit significantly accelerated rates of evolution in the human lineage (haDHSs). Furthermore, we discovered 31 human-specific potential transcription factor motifs within haDHSs, including the KROX and SP1, that both interact with HIV-1. Importantly, the corresponding haDHS was correlated with antiviral factor TRIM23. Thus, our results suggested that some viruses may contribute, through regulatory DNA differences, to organismal evolution by mediating TRIM gene expression to escape immune surveillance.

Original languageEnglish (US)
Article number20161602
JournalProceedings of the Royal Society B: Biological Sciences
Volume283
Issue number1840
DOIs
StatePublished - Oct 12 2016

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Environmental Science(all)
  • Agricultural and Biological Sciences(all)

Keywords

  • DNase i hypersensitive sites
  • Positive selection
  • Primate genome
  • Regulatory variation
  • Tripartite motif-containing protein family

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