Adaptive evolution in two large families of ubiquitin-ligase adapters in nematodes and plants.

Host-pathogen arms races can result in adaptive evolution (positive selection) of host genes that mediate pathogen recognition and defense. To identify such genes in nematodes, I used maximum-likelihood analysis of codon evolution to survey all paralogous gene groups in Caenorhabditis elegans. This survey found robust evidence of positive selection in two classes of genes not previously implicated in pathogen defense. Both classes of genes encode ubiquitin-dependent proteasome adapters, which recruit diverse substrate proteins for poly-ubiquitination and proteolysis by Cullin-E3 ubiquitin-ligase complexes. The adapter proteins are members of the F-box superfamily and the MATH-BTB family, which consist of a conserved Cullin-binding domain and a variable substrate-binding domain. Further analysis showed that most of the approximately 520 members of the F-box superfamily and approximately 50 members of the MATH-BTB family in C. elegans are under strong positive selection at sites in their substrate-binding domains but not in their Cullin-binding domains. Structural modeling of positively selected sites in MATH-BTB proteins suggests that they are concentrated in the MATH peptide-binding cleft. Comparisons among three Caenorhabditis species also indicate an extremely high rate of gene duplication and deletion (birth-death evolution) in F-box and MATH-BTB families. Finally, I found strikingly similar patterns of positive selection and birth-death evolution in the large F-box superfamily in plants. Based on these patterns of molecular evolution, I propose that most members of the MATH-BTB family and the F-box superfamily are adapters that target foreign proteins for proteolysis. I speculate that this system functions to combat viral pathogens or bacterial protein toxins.

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