PT  - JOURNAL ARTICLE
AU  - Núria Radó-Trilla
AU  - Krisztina Arató
AU  - Cinta Pegueroles
AU  - Alicia Raya
AU  - Susana de la Luna
AU  - M. Mar Albà
TI  - Key role of amino acid repeat expansions in the functional diversification of duplicated transcription factors
AID  - 10.1101/014910
DP  - 2015 Jan 01
TA  - bioRxiv
PG  - 014910
4099  - http://biorxiv.org/content/early/2015/02/05/014910.short
4100  - http://biorxiv.org/content/early/2015/02/05/014910.full
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. Here we investigate the role of amino acid tandem repeat expansions in the functional diversification of TF families originated at the 2R-WGD. We find that the number of low-complexity regions (LCRs) in duplicated gene copies is significantly higher than the number in single-copy TFs evolved during the same period of time. Overall, nearly half of the TF gene families (107 out of 237) have gained novel LCRs in one or more gene copies since the 2R-WGD, compared to only 15 of the 115 non-duplicated genes used as a control. In addition, duplicated TF preferentially accumulate certain repeat types, such as those enriched in alanine or glycine. We experimentally test the role of alanine repeats in two different TF gene families, LHX2/LHX9 and PHOX2A/PHOX2B. In both cases, the gain of the alanine repeat in one of the copies significantly increases the capacity of the protein to activate transcription. Taken together, the results support a key role of LCRs in the functional diversification of duplicated TFs.