Decreased Transcription Factor Binding Levels Nearby Primate Pseudogenes Suggest Regulatory Degeneration

Mol Biol Evol. 2016 Jun;33(6):1478-85. doi: 10.1093/molbev/msw030. Epub 2016 Feb 16.

Abstract

Characteristics of pseudogene degeneration at the coding level are well-known, such as a shift toward neutral rates of nonsynonymous substitutions and gain of frameshift mutations. In contrast, degeneration of pseudogene transcriptional regulation is not well understood. Here, we test two predictions of regulatory degeneration along a pseudogenized lineage: 1) Decreased transcription factor (TF) binding and 2) accelerated evolution in putative cis-regulatory regions.We find evidence for decreased TF binding levels nearby two primate pseudogenes compared with functional liver genes. However, the majority of TF-bound sequences nearby pseudogenes do not show evidence for lineage-specific accelerated rates of evolution. We conclude that decreases in TF binding level could be a marker for regulatory degeneration, while sequence degeneration in primate cis-regulatory modules may be obscured by background rates of TF binding site turnover.

Keywords: ChIP-seq; histone modifications.; neutral evolution; pseudoenhancer; regulatory evolution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Evolution
  • Evolution, Molecular
  • Gene Expression Regulation*
  • Humans
  • Macaca
  • Models, Genetic
  • Primates / genetics*
  • Protein Binding
  • Pseudogenes
  • Regulatory Elements, Transcriptional*
  • Sequence Alignment / methods
  • Sequence Analysis, DNA / methods
  • Transcription Factors / genetics

Substances

  • Transcription Factors