Expansion of signaling genes for adaptive immune system evolution in early vertebrates

The adaptive immune system (AIS) of jawed vertebrates is a sophisticated system mediated by numerous genes in specialized cells. Phylogenetic analysis indicates that emergence of the AIS followed the occurrence of two rounds of whole-genome duplication (2R-WGD) in early vertebrates, but little direct evidence linking these two events is available.

We examined the relationship between 2R-WGD and the gain of AIS-related functions by numerous genes. To analyze the evolution of the many genes related to signal transduction in the AIS (defined as AIS genes), we identified groups of genes (defined as AIS subfamilies) that included at least one human AIS gene, its paralogs (if any), and its Drosophila ortholog(s). Genomic mapping revealed that numerous pairs of AIS genes and their paralogs were part of paralogons - series of paralogous regions that derive from a common ancestor - throughout the human genome, indicating that the genes were retained as duplicates after 2R-WGD. Outgroup comparison analysis revealed that subfamilies in which human and fly genes shared a nervous system-related function were significantly enriched among AIS subfamilies, as compared with the overall incidence of shared nervous system-related functions among all subfamilies in bilaterians. This finding statistically supports the hypothesis that AIS-related signaling genes were ancestrally involved in the nervous system of urbilaterians.

The current results suggest that 2R-WGD played a major role in the duplication of many signaling genes, ancestrally used in nervous system development and function, that were later co-opted for new functions during evolution of the AIS.