title: Reassessing the "duon" hypothesis of protein evolution.
abstract: There are two distinct types of DNA sequences, namely coding sequences and regulatory sequences, in a genome. A recent study of the occupancy of transcription factors (TFs) in human cells suggested that protein-coding sequences also serve as the codes of TF occupancy, and proposed a "duon" hypothesis in which up to 15% of codons of human protein genes are constrained by the additional coding requirements that regulate gene expression. This hypothesis challenges our basic understanding on the human genome. We reanalyzed the data and found that the previous study was confounded by ascertainment bias related to base composition. Using an unbiased comparison in which G/C and A/T sites are considered separately, we reveal a similar level of conservation between TF-bound codons and TF-depleted codons, suggesting largely no extra purifying selection provided by the TF occupancy on the codons of human genes. Given the generally short binding motifs of TFs and the open chromatin structure during transcription, we argue that the occupancy of TFs on protein-coding sequences is mostly passive and evolutionarily neutral, with to-be-determined functions in the regulation of gene expression.
authors.affiliation: State Key Laboratory of Biocontrol, Cooperative Innovation Center for High Performance Computing, College of Ecology and Evolution, Sun Yat-sen University, Guangzhou, China Guangdong Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-Sen University, Guangzhou, China xingk@mail.sysu.edu.cn.
authors.forename: Ke
authors.initials: K
authors.lastname: Xing
authors.affiliation: State Key Laboratory of Biocontrol, Cooperative Innovation Center for High Performance Computing, College of Ecology and Evolution, Sun Yat-sen University, Guangzhou, China Guangdong Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Xionglei
authors.initials: X
authors.lastname: He
mesh_terms: D000818:Animals; D001483:Base Sequence; D003062:Codon; D019143:Evolution, Molecular; D005091:Exons; D006801:Humans; D011506:Proteins / Q000235:genetics*; D050436:Regulatory Elements, Transcriptional; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D003062:Codon; D011506:Proteins; D014157:Transcription Factors
keywords: TF occupancy; dual-used codons; protein evolution