PT - JOURNAL ARTICLE AU - Jian-Rong Yang AU - Calum Maclean AU - Chungoo Park AU - Huabin Zhao AU - Jianzhi Zhang TI - Intra- and inter-specific variations of gene expression levels in yeast are largely neutral AID - 10.1101/089995 DP - 2016 Jan 01 TA - bioRxiv PG - 089995 4099 - http://biorxiv.org/content/early/2016/11/28/089995.short 4100 - http://biorxiv.org/content/early/2016/11/28/089995.full AB - It is commonly, although not universally, accepted that most intra- and inter-specific genome sequence variations are more or less neutral, whereas a large fraction of organism-level phenotypic variations are adaptive. Gene expression levels are molecular phenotypes that bridge the gap between genotypes and corresponding organism-level phenotypes. Yet, it is unknown whether natural variations in gene expression levels are mostly neutral or adaptive. Here we address this fundamental question by genome-wide profiling and comparison of gene expression levels in nine yeast strains belonging to three closely related Saccharomyces species and originating from five different ecological environments. We find that the transcriptome-based clustering of the nine strains approximates the genome sequence-based phylogeny irrespective of their ecological environments. Remarkably, only ∼0.5% of genes exhibit similar expression levels among strains from a common ecological environment, no greater than that among strains with comparable phylogenetic relationships but different environments. These and other observations strongly suggest that most intra- and inter-specific variations in yeast gene expression levels result from the accumulation of random mutations rather than environmental adaptations. This finding has profound implications for understanding the driving force of gene expression evolution, genetic basis of phenotypic adaptation, and general role of stochasticity in evolution.