Comparative regulomics supports pervasive selection on gene dosage following whole genome duplication

Eric B. Rondeau,Torgeir R. Hvidsten,Manu Kumar Gundappa,Gareth B. Gillard,Lars Grønvold,Daniel J. Macqueen,Øystein Monsen,Ben F. Koop,Rori V. Rohlfs,Matilde Mengkrog Holen,Line L. Røsæg,John Mendoza,Simen R. Sandve

doi:10.1186/s13059-021-02323-0

Abstract

BackgroundWhole genome duplication (WGD) events have played a major role in eukaryotic genome evolution, but the consequence of these extreme events in adaptive genome evolution is still not well understood. To address this knowledge gap, we used a comparative phylogenetic model and transcriptomic data from seven species to infer selection on gene expression in duplicated genes (ohnologs) following the salmonid WGD 80–100 million years ago.ResultsWe find rare cases of tissue-specific expression evolution but pervasive expression evolution affecting many tissues, reflecting strong selection on maintenance of genome stability following genome doubling. Ohnolog expression levels have evolved mostly asymmetrically, by diverting one ohnolog copy down a path towards lower expression and possible pseudogenization. Loss of expression in one ohnolog is significantly associated with transposable element insertions in promoters and likely driven by selection on gene dosage including selection on stoichiometric balance. We also find symmetric expression shifts, and these are associated with genes under strong evolutionary constraints such as ribosome subunit genes. This possibly reflects selection operating to achieve a gene dose reduction while avoiding accumulation of “toxic mutations”. Mechanistically, ohnolog regulatory divergence is dictated by the number of bound transcription factors in promoters, with transposable elements being one likely source of novel binding sites driving tissue-specific gains in expression.ConclusionsOur results imply pervasive adaptive expression evolution following WGD to overcome the immediate challenges posed by genome doubling and to exploit the long-term genetic opportunities for novel phenotype evolution.

Highlights

Whole genome duplication (WGD) events have played a major role in eukaryotic genome evolution, but the consequence of these extreme events in adaptive genome evolution is still not well understood
The crux of this model is that it allows us to evaluate if changes in expression evolution deviate from the null hypothesis of stabilizing selection, and thereby identify putative adaptive shifts in expression regulation. We used this model to analyze the liver transcriptome of four salmonids and three non-salmonid fish species to assess the impact of the 80–100million-year-old salmonid-specific WGD (Ss4R) [24, 25]. We find that this WGD led to a burst of gene expression evolution, leading to rare tissue-specific gains in expression and pervasive tissue non-specific dosage selection, reflecting both adaptive possibilities afforded by genome doubling and immediate challenges that must be overcome to succeed as a polyploid lineage
We find strong evidence for dosage selection following WGD on genes involved in basic cellular maintenance and cell division

Summary

Introduction

Whole genome duplication (WGD) events have played a major role in eukaryotic genome evolution, but the consequence of these extreme events in adaptive genome evolution is still not well understood. Whole genome duplication (WGD) events have played a major role in eukaryotic evolution by increasing genomic complexity and functional redundancy [1] This can allow gene duplicates (referred to as ohnologs) to escape selective constraints and thereby accumulate previously forbidden mutations that may become adaptive [2]. Ohnolog regulatory evolution is mostly asymmetric, with one copy retaining an ancestral-like regulation, and the other copy losing and/or gaining expression in one or more tissue [12] This observation can be reconciled with adaptive evolution of gene regulatory phenotypes following WGD, methodological limitations have made it difficult to distinguish between the outcomes of selection and neutral drift [12, 21]

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Results

Conclusion