RT Journal Article
SR Electronic
T1 Key role of amino acid repeat expansions in the functional diversification of duplicated transcription factors
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 014910
DO 10.1101/014910
A1 Núria Radó-Trilla
A1 Krisztina Arató
A1 Cinta Pegueroles
A1 Alicia Raya
A1 Susana de la Luna
A1 M.Mar Albà
YR 2015
UL http://biorxiv.org/content/early/2015/02/23/014910.abstract
AB The high regulatory complexity of vertebrates has been related to two closely spaced whole genome duplications (2R-WGD) that occurred before the divergence of the major vertebrate groups. Following these events, many developmental transcription factors (TFs) were retained in multiple copies and subsequently specialized in diverse functions, whereas others reverted to their singleton state. TFs are known to be generally rich in amino acid repeats or low-complexity regions (LCRs), such as polyalanine or polyglutamine runs, which can evolve rapidly and potentially influence the transcriptional activity of the protein. Here we test the hypothesis that LCRs have played a major role in the diversification of TF gene duplicates. We find that nearly half of the TF gene families (107 out of 237) originated during the 2R-WGD contain LCRs, compared to only a small percentage of the non-duplicated TF genes used as a control (15 out of 115). At the individual gene level, we observe that twice as many duplicated TFs have gained LCRs as non-duplicated TFs. In addition, duplicated TFs preferentially accumulate certain LCR types, the most prominent of which are alanine repeats. We experimentally test the role of alanine-rich LCRs in two different TF gene families, PHOX2A/PHOX2B and LHX2/LHX9. In both cases, the presence of the alanine-rich LCR in one of the copies (PHOX2B and LHX2) significantly increases the capacity of the TF to activate transcription. Taken together, the results provide strong evidence that LCRs are important driving forces of evolutionary change in duplicated genes.