Genetic drift dominates genome-wide regulatory evolution following an ancient whole genome duplication in Atlantic salmon

Abstract

Whole genome duplications (WGD) have been considered as springboards that potentiate lineage diversification through increasing functional redundancy. Divergence in gene regulatory elements is a central mechanism for evolutionary diversification, yet the patterns and processes governing regulatory divergence following events that lead to massive functional redundancy, such as WGD, remain largely unknown. We studied the patterns of divergence and strength of natural selection on regulatory elements in the Atlantic salmon (Salmo salar) genome, which has undergone WGD 100-80 Mya. Using ChIPmentation, we first show that H3K27ac, a histone modification typical to enhancers and promoters, is associated with genic regions, tissue specific transcription factor binding motifs, and with gene transcription levels in immature testes. Divergence in transcription between duplicated genes from WGD (ohnologs) correlated with difference in the number of proximal regulatory elements, but not with promoter elements, suggesting that functional divergence between ohnologs after WGD is mainly driven by enhancers. By comparing H3K27ac regions between duplicated genome blocks, we further show that a longer polyploid state post-WGD has constrained asymmetric regulatory evolution. Patterns of genetic diversity across natural populations inferred from re-sequencing indicate that recent evolutionary pressures on H3K27ac regions are dominated by largely neutral evolution. In sum, our results suggest that post-WGD functional redundancy in regulatory elements continues to have an impact on the evolution of the salmon genome, promoting largely neutral evolution of regulatory elements despite their association with transcription levels. These results highlight a case where genome-wide regulatory evolution following an ancient WGD is dominated by genetic drift. Significance statementRegulatory evolution following whole genome duplications (WGD) has been investigated at the gene expression level, but studies of the regulatory elements that control expression have been lacking. By investigating regulatory elements in the Atlantic salmon genome, which has undergone a whole genome duplication 100-80 million years ago, we discovered patterns suggesting that neutral divergence is the prevalent mode of regulatory element evolution post-WGD. Our results suggest mechanisms for explaining the prevalence of asymmetric gene expression evolution following whole genome duplication, as well as the mismatch between evolutionary rates in enhancers versus that of promoters.