Differences in duplication age distributions between human GPCRs and their downstream genes from a network prospective

How gene duplication has influenced the evolution of gene networks is one of the core problems in evolution. Current duplication-divergence theories generally suggested that genes on the periphery of the networks were preferentially retained after gene duplication. However, previous studies were mostly based on gene networks in invertebrate species, and they had the inherent shortcoming of not being able to provide information on how the duplication-divergence process proceeded along the time axis during major speciation events.

In this study, we constructed a model system consisting of human G protein-coupled receptors (GPCRs) and their downstream genes in the GPCR pathways. These two groups of genes offered a natural partition of genes in the peripheral and the backbone layers of the network. Analysis of the age distributions of the duplication events in human GPCRs and "downstream genes" gene families indicated that they both experienced an explosive expansion at the time of early vertebrate emergence. However, we found only GPCR families saw a continued expansion after early vertebrates, mostly prominently in several small subfamilies of GPCRs involved in immune responses and sensory responses.

In general, in the human GPCR model system, we found that the position of a gene in the gene networks has significant influences on the likelihood of fixation of its duplicates. However, for a super gene family, the influence was not uniform among subfamilies. For super families, such as GPCRs, whose gene basis of expression diversity was well established at early vertebrates, continued expansions were mostly prominent in particular small subfamilies mainly involved in lineage-specific functions.