Abstract
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.