Coexpression of Linked Gene Pairs Persists Long after Their Separation

In many eukaryotes, physically linked gene pairs tend to be coexpressed. However, it is still controversial to what extent this neighbor coexpression is maintained by selection and to what extent it is nonselective, purely mechanistic “leaky expression.” Here, we analyze expression patterns of gene pairs that have lost their linkage in the evolution of Saccharomyces cerevisiae since its last common ancestor with Kluyveromyces waltii or that were never linked in the S. cerevisiae lineage but became neighbors in a related yeast. We demonstrate that coexpression of many linked genes is retained long after their separation and is thus likely to be functionally important. In addition, unlinked gene pairs that recently became neighbors in other yeast species tend to be coexpressed in S. cerevisiae. This suggests that natural selection often favors chromosomal rearrangements in which coexpressed genes become neighbors. Contrary to previous suggestions, selectively favorable coexpression appears not to be restricted to bidirectional promoters.