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.

Highlights

  • To maintain homeostasis or to undergo specified developmental decisions, an organism must be able to respond rapidly to a variety of environmental changes

  • We identified nine annotated pseudogenes duplicated from protein-coding F-box genes and 21 corresponding homologous DNA regions (Table S2)

  • Lineage-specific gene tandem duplication, mRNA-mediated retrotransposition, and gene loss contributed to F-box gene number variation in the eight organisms examined in this study

Read more

Summary

Introduction

To maintain homeostasis or to undergo specified developmental decisions, an organism must be able to respond rapidly to a variety of environmental changes. Protein ubiquitination is an enzymatic cascade in which ubiquitin is activated by an E1 enzyme, transferred to an E2 ubiquitin-conjugating enzyme and transferred to a substrate selected by an E3 ubiquitin ligase [2]. An E3 ubiquitin ligase must rapidly and uniquely bind to target proteins in response to stimuli. One of the best characterized E3s are the S phase kinase-associated protein 1 (SKP1)–cullin 1 (CUL1)–F-box protein (SCF) type ubiquitin ligase complexes [3]. CUL1 serves as a scaffold for assembling the ubiquitin-conjugating machinery. The C-terminus of CUL1 interacts with the RING-box protein 1 (RBX1), whereas its N- terminus binds to SKP1, which, in turn, binds to an F-box protein

Methods
Results
Discussion
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call