Divergence in paralogous transcription factor specificity affect cell cycle progression in closely related species

Changes in gene expression regulation play a major rule in evolution and phenotypic diversity. Previous studies have systematically shown extensive variation in gene expression between close species, but lack the context of phenotypic variations in the molecular level. Here we study two closely related budding yeast species that differ in cell cycle phase-duration and growth morphology, to decipher how regulation of these processes diverged through evolution.

In this study, we profile divergence in regulatory processes by measuring the transcriptome and in-vivo binding of cycling transcription factors (TFs) in the related species. Analysis of an interspecific hybrid distinguish local mutations (cis) from distant ones (trans). A pair of paralog TFs raise interest, where binding patterns of the two factors are similar in one species but diverge in the other. These duplicate TFs, Ace2 and Swi5, affects the duration of G1 phase and activate the transcription of mitotic exit genes, which expression highly differs between the species. We find that binding of Ace2 has diverged between the species, and is dependent on the activity of other TF pair, Fkh1/2, which mediate its binding to specific promoters that are not shared with its paralog. Our results show that TF binding can rapidly diverge in evolution through trans mutations, tinkering core biological processes such as the cell cycle.