The effects of de novo mutation on gene expression and the consequences for fitness in Chlamydomonas reinhardtii

Abstract

AbstractMutation is the ultimate source of genetic variation, the bedrock of evolution, but predicting the consequences of new mutations remains a challenge in biology. Gene expression provides a potential link between genotype and phenotype with growing interest in the influence of mutation on expression expanding our understanding of evolutionary changes and disease. Yet, the total amount of expression variation created by mutations; the aspects of buffering in the regulatory network or specific genes against mutation; and the fitness consequences of mutational changes to expression remain relatively unexplored. Here, we investigate the effects of >2600 de novo mutations on gene expression across the transcriptomes of 28 mutation accumulation lines derived from two independent wild-type genotypes of the green algae Chlamydomonas reinhardtii. We found a much larger number of differentially expressed genes than mutations implying large effect trans-acting mutations, but also show evidence for some smaller effect cis-acting mutations. The larger influence of trans-acting mutations likely eliminated any correlation between the number of mutations and the extent of expression divergence in each line. We also found that the per generation increase in expression variance is substantially higher in C. reinhardtii than other species, which is in part due to the lower number of mutations per generation seen in unicellular organisms. Finally, we also demonstrate that the extent of expression divergence negatively correlates with overall fitness, providing direct evidence of stabilizing selection on gene expression.