Searching protein space for ancient sub-domain segments

Evolutionary processes that formed the current protein universe left their traces, among them homologous segments that recur, or are ‘reused,’ in multiple proteins. These reused segments, called ‘themes,’ can be found at various scales, the best known of which is the domain. Yet, recent studies have begun to focus on the evolutionary insights that can be derived from sub-domain-scale themes, which are candidates for traces of more ancient events. Characterizing these may provide clues to the emergence of domains. Particularly interesting are themes that are reused across dissimilar contexts, that is, where the rest of the protein domain differs. We survey computational studies identifying reused themes within different contexts at the sub-domain level.