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Meeting Abstract
26.7 Monday, Jan. 5 The Origin of Conserved Protein Domains and Amino Acid Repeats Via Adaptive Competition RORICK, M.M.*; WAGNER, G.P.; Yale University; Yale University molly.rorick@yale.edu
Some proteins, such as homeodomain transcription factors, contain highly conserved regions of sequence. It has been recently suggested that multiple conserved functional domains overlap and together explain the high conservation of these regions. However, we are still left with the question of why so many conserved functions cluster together in one relatively small region of the protein. Is there an evolutionary mechanism that can produce this kind of clustering? Here we have modeled one such mechanism: conserved functional domains get displaced from the more variable parts of the molecule that are undergoing adaptive evolution because poorly optimized novel functions in variable regions generally out-compete conserved functions for control over amino acid identity. We also studied the evolution of single amino acid tandem repeats (a.k.a. homopeptides), which are common in eukaryotic proteins and especially prevalent in transcription factors. Some homopeptides are encoded by nonhomogenous mixtures of synonymous codons, so their presence cannot be explained by a neutral process slippage. Further, Mularoni et al. (2007) find that the most constrained proteins in fact have the greatest number of repeats. Although it is clear that selection is playing a role in the evolution of such repeats, the exact mechanism by which they arise remains unclear. Our model provides two ways to explain their origin, maintenance and over-representation in highly conserved proteins. We demonstrate that either competition between multiple functional domains for space within a sequence, or reuse of a sequence for many functions over time, can cause the evolution of such repeats. Both of these causal processes are especially characteristic of multi-functional proteins such as homeodomain transcription factors.