TY - JOUR TI - Evolution of binding preferences among whole-genome duplicated transcription factors AU - Gera, Tamar AU - Jonas, Felix AU - More, Roye AU - Barkai, Naama A2 - Landry, Christian R A2 - Struhl, Kevin A2 - Kuzmin, Elena VL - 11 PY - 2022 DA - 2022/04/11 SP - e73225 C1 - eLife 2022;11:e73225 DO - 10.7554/eLife.73225 UR - https://doi.org/10.7554/eLife.73225 AB - Throughout evolution, new transcription factors (TFs) emerge by gene duplication, promoting growth and rewiring of transcriptional networks. How TF duplicates diverge was studied in a few cases only. To provide a genome-scale view, we considered the set of budding yeast TFs classified as whole-genome duplication (WGD)-retained paralogs (~35% of all specific TFs). Using high-resolution profiling, we find that ~60% of paralogs evolved differential binding preferences. We show that this divergence results primarily from variations outside the DNA-binding domains (DBDs), while DBD preferences remain largely conserved. Analysis of non-WGD orthologs revealed uneven splitting of ancestral preferences between duplicates, and the preferential acquiring of new targets by the least conserved paralog (biased neo/sub-functionalization). Interactions between paralogs were rare, and, when present, occurred through weak competition for DNA-binding or dependency between dimer-forming paralogs. We discuss the implications of our findings for the evolutionary design of transcriptional networks. KW - transcription factors KW - functional divergence KW - whole genome duplication KW - gene regulation KW - DNA binding KW - paralogs JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -