Modules, multidomain proteins and organismic complexity

Originally the term ‘protein module’ was coined to distinguish mobile domains that frequently occur as building blocks of diverse multidomain proteins from ‘static’ domains that usually exist only as stand‐alone units of single‐domain proteins. Despite the widespread use of the term ‘mobile domain’, the distinction between static and mobile domains is rather vague as it is not easy to quantify the mobility of domains. In the present work we show that the most appropriate measure of the mobility of domains is the number of types of local environments in which a given domain is present. Ranking of domains with respect to this parameter in different evolutionary lineages highlighted marked differences in the propensity of domains to form multidomain proteins. Our analyses have also shown that there is a correlation between domain size and domain mobility: smaller domains are more likely to be used in the construction of multidomain proteins, whereas larger domains are more likely to be static, stand‐alone domains. It is also shown that shuffling of a limited set of modules was facilitated by intronic recombination in the metazoan lineage and this has contributed significantly to the emergence of novel complex multidomain proteins, novel functions and increased organismic complexity of metazoa.