title: Decreased Transcription Factor Binding Levels Nearby Primate Pseudogenes Suggest Regulatory Degeneration.
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.
authors.affiliation: Department of Ecology and Evolutionary Biology, University of Toronto, Toronto, ON, Canada.
authors.forename: Gavin M
authors.initials: GM
authors.lastname: Douglas
authors.affiliation: Genetics and Genome Biology Program, SickKids Research Institute, Toronto, ON, Canada Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Wilson
authors.affiliation: Department of Ecology and Evolutionary Biology, University of Toronto, Toronto, ON, Canada Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada alan.moses@utoronto.ca.
authors.forename: Alan M
authors.initials: AM
authors.lastname: Moses
mesh_terms: D000818:Animals; D005075:Biological Evolution; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D006801:Humans; D008251:Macaca; D008957:Models, Genetic; D011323:Primates / Q000235:genetics*; D011485:Protein Binding; D011544:Pseudogenes; D050436:Regulatory Elements, Transcriptional; D016415:Sequence Alignment / Q000379:methods; D017422:Sequence Analysis, DNA / Q000379:methods; D014157:Transcription Factors / Q000235:genetics
chemical_list: D014157:Transcription Factors
keywords: ChIP-seq; histone modifications.; neutral evolution; pseudoenhancer; regulatory evolution