Inter- and intra-domain horizontal gene transfer, gain-loss asymmetry and positive selection mark the evolutionary history of the CBM14 family.

Protein-carbohydrate interactions are ubiquitous in nature and at the core of many physiological processes of profound importance to health and disease. Specificity in protein-carbohydrate interactions is conferred by carbohydrate-binding modules (CBMs) that can accurately discriminate among the multitude of saccharides found in nature, thus targeting proteins to their particular substrates. Family 14 carbohydrate-binding modules (CBM14s), more specifically, are short modules that bind explicitly to chitin, the second most abundant carbohydrate in nature. Although considerable effort has been placed in elucidating protein-carbohydrate interactions at the molecular level for biological and biotechnological applications, in contrast the evolutionary relationships among these modules are minimally understood. Using the CBM14 family as an example, here we describe one of the first global molecular evolutionary analyses of a CBM family across all domains of life, with an emphasis on its origin, taxonomic distribution and pattern of diversification as a result of gene and module duplication, and positive selection. Our genome-wide searches recovered an impressive number of CBM14s from diverse lineages across nearly all domains of life. However, their highly disseminated distribution in taxa outside the Opisthokonta group strongly suggests a later evolutionary origin and elevated rates of inter- and intra-domain horizontal gene transfer. Moreover, accelerated rates of asymmetric gains and losses reveal a dynamic mode of birth-and-death evolution, whereas positive selection acting on paralogous CBM14-containing proteins suggest changes in substrate specificity and an increase in the functional promiscuity of this ancient CBM family. The importance of these results is discussed.