Abstract
Homopolymeric amino acid repeats (AARs) like polyalanine (polyA) and polyglutamine (polyQ) in some developmental proteins (DPs) regulate certain aspects of organismal morphology and behavior, suggesting an evolutionary role for AARs as developmental “tuning knobs.” It is still unclear, however, whether these are occasional protein-specific phenomena or hints at the existence of a whole AAR-based regulatory system in DPs. Using novel approaches to trace their functional and evolutionary history, we find quantitative evidence supporting a generalized, combinatorial role of AARs in developmental processes with evolutionary implications. We observe nonrandom AAR distributions and combinations in HOX and other DPs, as well as in their interactomes, defining elements of a proteome-wide combinatorial functional code whereby different AARs and their combinations appear preferentially in proteins involved in the development of specific organs/systems. Such functional associations can be either static or display detectable evolutionary dynamics. These findings suggest that progressive changes in AAR occurrence/combination, by altering embryonic development, may have contributed to taxonomic divergence, leaving detectable traces in the evolutionary history of proteomes. Consistent with this hypothesis, we find that the evolutionary trajectories of the 20 AARs in eukaryotic proteomes are highly interrelated and their individual or compound dynamics can sharply mark taxonomic boundaries, or display clock-like trends, carrying overall a strong phylogenetic signal. These findings provide quantitative evidence and an interpretive framework outlining a combinatorial system of AARs whose compound dynamics mark at the same time DP functions and evolutionary transitions.
Highlights
The evolutionary emergence of novel morphological and behavioral features in organisms constitutes a central biological problem (Gould 2002; Kirschner 2013), but the underlying genetic dynamics are only partially understood
We investigated the preferential associations of amino acid repeats (AARs) with specific developmental proteins (DPs) functions by determining whether protein sets associated with a specific developmental gene ontology (GO) term, or with a cluster of semantically related GO terms, contained a significant overrepresentation of AAR-containing proteins, as assessed by means of v2 tests on 2 Â 2 contingency tables followed by a Benjamini-Hochberg correction for multiple testing (FDR 1⁄4 0.05; Benjamini and Hochberg 1995)
Because the known AARs with regulatory roles in development are in transcription factors (TFs) belonging to the HOX, POU, and other families (Treier et al 1989; Galant and Carroll 2002; Fondon and Garner 2004; Anan et al 2007; O’Malley and Banks 2008; Chew et al 2012; Nasu et al 2014; Hashizume et al 2018), we focused our investigation on a set of TFs with known developmental roles and belonging to relatively large and functionally characterized families
Summary
The evolutionary emergence of novel morphological and behavioral features in organisms constitutes a central biological problem (Gould 2002; Kirschner 2013), but the underlying genetic dynamics are only partially understood. Replication slippage or unequal crossing-over in the coding part of developmental genes can induce the expansion or contraction of triplet repeats coding for homopolymeric amino acid repeats (AARs; Gemayel et al 2010; Haerty and Golding 2010a, 2010b). Despite their abundance especially in developmental and nervous system proteins, often in pairwise or more complex combination (Green and Wang, 1994; Karlin and Burge 1996; Alba et al 2007; Pelassa et al 2014), their structures and possible functions are only partially understood.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
