PT  - JOURNAL ARTICLE
AU  - Gavin M. Douglas
AU  - Michael D. Wilson
AU  - Alan M. Moses
TI  - Decreased transcription factor binding levels nearby primate pseudogenes suggests regulatory degeneration
AID  - 10.1101/024026
DP  - 2015 Jan 01
TA  - bioRxiv
PG  - 024026
4099  - http://biorxiv.org/content/early/2015/08/06/024026.short
4100  - http://biorxiv.org/content/early/2015/08/06/024026.full
AB  - Characteristics of pseudogene degeneration at the coding level are well-known, such as a shift towards 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 the pseudogenized lineage: (1) decreased transcription factor binding and (2) accelerated evolution in putative cis-regulatory regions.We find evidence for decreased TF binding levels nearby two primate pseudogenes compared to functional liver genes. We also find evidence for pseudogene-lineage-specific relaxation of sequence constraint on a fragment of the promoter of the primate pseudogene urate oxidase (Uox) and a nearby cis-regulatory module (CRM). 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 most CRMs may be obscured by background rates of TF binding site turnover.