Quantifying the mechanisms of domain gain in animal proteins

Here we show that the major mechanism for gains of new domains in metazoan proteins is likely to be gene fusion through joining of exons from adjacent genes, possibly mediated by non-allelic homologous recombination. Retroposition and insertion of exons into ancestral introns through intronic recombination are, in contrast to previous expectations, only minor contributors to domain gains and have accounted for less than 1% and 10% of high confidence domain gain events, respectively. Additionally, exonization of previously non-coding regions appears to be an important mechanism for addition of disordered segments to proteins. We observe that gene duplication has preceded domain gain in at least 80% of the gain events.The interplay of gene duplication and domain gain demonstrates an important mechanism for fast neofunctionalization of genes.Protein domains are fundamental and largely independent units of protein structure and function that occur in a number of different combinations or domain architectures [1]. Most proteins have two or more domains [2] and, interestingly, more complex organisms have more complex domain architectures, as well as a greater variety of domain combinations [2-4]. A possible implication of this phenomenon is that new domain architectures have acted as drivers of the evolution of organismal complexity [3]. This is supported by a recent study that experimentally showed that recombination of domains encoded by genes that belong to the yeast mating pathway had a major influence on phenotype [5]. While there is evidence that in prokaryotes new domains are predominantly acquired through fusions of adjacent genes [6,7], determining the predominant molecular mechanisms that underlie gains of new domains in animals has been more challenging [3].The question of what mechanisms underlie domain gains is related to the question of what mechanisms underlie novel gene creation [3,8,9]. The recent increased availability of animal genome and transcriptome