Coding region structural heterogeneity and turnover of transcription start sites contribute to divergence in expression between duplicate genes

Background: Gene expression divergence is one manifestation of functional differences between duplicate genes. Although rapid accumulation of expression divergence between duplicate gene copies has been observed, the driving mechanisms behind this phenomenon have not been explored in detail. Results: We examine which factors influence expression divergence between human duplicate genes, utilizing the latest genome-wide data sets. We conclude that the turnover of transcription start sites between duplicate genes occurs rapidly after gene duplication and that gene pairs with shared transcription start sites have significantly higher expression similarity than those without shared transcription start sites. Moreover, we find that most (55%) duplicate gene pairs do not retain the same coding sequence structure between the two duplicate copies and this also contributes to divergence in their expression. Furthermore, the proportion of aligned sequences in cis-regulatory regions between the two copies is positively correlated with expression similarity. Surprisingly, we find no effect of copy-specific transposable element insertions on the divergence of duplicate gene expression. Conclusions: Our results suggest that turnover of transcription start sites, structural heterogeneity of coding sequences, and divergence of cis-regulatory regions between copies play a pivotal role in determining the expression divergence of duplicate genes.