Tracing the paths of modular evolution by quantifying rearrangement events of protein domains.

Background: Protein evolution is central to molecular adaptation and largely characterized by modular rearrangements of domains, the evolutionary and structural building blocks of proteins. Genetic events underlying protein rearrangements are relatively rare compared to changes of amino-acids. Therefore, these events can be used to characterize and reconstruct major events of molecular adaptation by comparing large data sets of proteomes.

Results: Here we determine, at unprecedented completeness, the rates of fusion, fission, emergence and loss of domains in five eukaryotic clades (monocots, eudicots, fungi, insects, vertebrates). By characterizing rearrangements that were previously considered "ambiguous" or "complex" we raise the fraction of resolved rearrangement events from previously ca. 60% to around 92%. We exemplify our method by analyzing the evolutionary histories of protein rearrangements in (i) the extracellular matrix, (ii) innate immunity across Eukaryota, Metazoa, and Vertebrata, and (iii) Toll-Like-Receptors in the innate immune system of Eukaryota. In all three cases we can find hot-spots of rearrangement events in their phylogeny which (i) can be related with major events of adaptation and (ii) which follow the emergence of new domains which become integrated into existing arrangements.

Conclusion: Our results demonstrate that, akin to the change at the level of amino acids, domain rearrangements follow a clock-like dynamic which can be well quantified and supports the concept of evolutionary tinkering. While many novel domain emergence events are ancient, emerged domains are quickly incorporated into a great number of proteins. In parallel, the observed rates of emergence of new domains are becoming smaller over time.