Evolution of the F-Box Gene Family in Euarchontoglires: Gene Number Variation and Selection Patterns

Abstract

F-box proteins are substrate adaptors used by the SKP1–CUL1–F-box protein (SCF) complex, a type of E3 ubiquitin ligase complex in the ubiquitin proteasome system (UPS). SCF-mediated ubiquitylation regulates proteolysis of hundreds of cellular proteins involved in key signaling and disease systems. However, our knowledge of the evolution of the F-box gene family in Euarchontoglires is limited. In the present study, 559 F-box genes and nine related pseudogenes were identified in eight genomes. Lineage-specific gene gain and loss events occurred during the evolution of Euarchontoglires, resulting in varying F-box gene numbers ranging from 66 to 81 among the eight species. Both tandem duplication and retrotransposition were found to have contributed to the increase of F-box gene number, whereas mutation in the F-box domain was the main mechanism responsible for reduction in the number of F-box genes, resulting in a balance of expansion and contraction in the F-box gene family. Thus, the Euarchontoglire F-box gene family evolved under a birth-and-death model. Signatures of positive selection were detected in substrate-recognizing domains of multiple F-box proteins, and adaptive changes played a role in evolution of the Euarchontoglire F-box gene family. In addition, single nucleotide polymorphism (SNP) distributions were found to be highly non-random among different regions of F-box genes in 1092 human individuals, with domain regions having a significantly lower number of non-synonymous SNPs.

Functional assignment to positively selected sites in the core type III effector RipG7 from Ralstonia solanacearum

“…Co‐immunoprecipitation experiments allowed us to rule out the possibility that the absence of complementation is a result of the absence of interaction with SKP1‐like (MSKa) for all but the phylotype II strain IPO1609. This result is in agreement with the fact that the LRR domains of Fbox proteins are key for the interaction with substrate proteins (Gagne et al ., ; Wang et al ., ). Our selection study on a global diversity set of 16 ripG7 orthologues further emphasizes the importance of this domain, as 10 of the 11 strongest candidate sites for positive selection were located in, or in between, LRR repeats.…”

“…Notably, the latter domains are very different, defining several families, with probably different target recognition, in a given organism (Xu et al, 2011). Among the Fbox proteins with a leucine-rich repeat (LRR) as C-terminal domain, there is evidence of positive selection on the LRR, suggesting diversification of target recognition (Wang et al, 2014). Other plant LRR-containing proteins, related to immunity functions, are also subject to strong evolutionary constraints.…”

“…Site 126 is the only non-LRR-located site and is surprisingly located in the Fbox domain for which the overall selection is, rather, purifying (Wang et al, 2014) (Fig. 4A).…”

Genome-Wide Characterization, Evolution, Structure, and Expression Analysis of the F-box Genes in Caenorhabditis

“…Although the prediction approach used here was di cult to avoid false negative F-box genes, it was widely applied in numerous studies [30][31][32]. In addition, identi cation of F-box genes in human using our approach is highly reliable [27]. Notably, the duplicates of F-box genes identi ed have diverged substantially at corresponding F-box domain region, which may contribute to their functional divergence.…”

“…However, in most of investigated animals, F-box genes are small in number and quite conserved among closely related species. For instance, F-box gene number varies from 66 to 81 in Euarchontoglires [27], and only 42-47 in 12 extant Drosophila species [28]. In contrast, F-box genes are massively expanded in Caenorhabditis, and the number of F-box genes are even more than one thousand [16].…”