Abstract

BackgroundThe mitogen activated protein kinases (MAPK) family pathway is implicated in diverse cellular processes and pathways essential to most organisms. Its evolution is conserved throughout the eukaryotic kingdoms. However, the detailed evolutionary history of the vertebrate MAPK family is largely unclear.Methodology/Principal FindingsThe MAPK family members were collected from literatures or by searching the genomes of several vertebrates and invertebrates with the known MAPK sequences as queries. We found that vertebrates had significantly more MAPK family members than invertebrates, and the vertebrate MAPK family originated from 3 progenitors, suggesting that a burst of gene duplication events had occurred after the divergence of vertebrates from invertebrates. Conservation of evolutionary synteny was observed in the vertebrate MAPK subfamilies 4, 6, 7, and 11 to 14. Based on synteny and phylogenetic relationships, MAPK12 appeared to have arisen from a tandem duplication of MAPK11 and the MAPK13-MAPK14 gene unit was from a segmental duplication of the MAPK11-MAPK12 gene unit. Adaptive evolution analyses reveal that purifying selection drove the evolution of MAPK family, implying strong functional constraints of MAPK genes. Intriguingly, however, intron losses were specifically observed in the MAPK4 and MAPK7 genes, but not in their flanking genes, during the evolution from teleosts to amphibians and mammals. The specific occurrence of intron losses in the MAPK4 and MAPK7 subfamilies might be associated with adaptive evolution of the vertebrates by enhancing the gene expression level of both MAPK genes.Conclusions/SignificanceThese results provide valuable insight into the evolutionary history of the vertebrate MAPK family.

Highlights

  • The mitogen activated protein kinase (MAPK) cascade consists of three protein kinases, mitogen activated protein kinases (MAPK), MAPK kinase (MAPKK) and MAPKK kinase (MAPKKK) [1]

  • In order to better understand the evolutionary history of the MAPK family in vertebrates, we generated a primary amino acid sequence data set covering mammals, birds, reptiles, amphibians and teleosts

  • We found that vertebrates had substantially more MAPK family members than invertebrates (Table 1), and the vertebrate MAPK family had been formed through multiple duplications at least prior to the diversification of teleosts (Figure 1)

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Summary

Introduction

The mitogen activated protein kinase (MAPK) cascade consists of three protein kinases, MAPK, MAPK kinase (MAPKK) and MAPKK kinase (MAPKKK) [1]. In the classical three-tiered MAPKKK–MAPKK–MAPK cascade, MAPKKKs phosphorylate and activate specific MAPKKs, which further phosphorylate and activate downstream MAPKs [2]. All eukaryotic cells use multiple MAP kinase modules for signal transduction and the MAPK pathways are involved in diverse cellular processes, including cell growth [3,4], migration [5], survival [6], mesoderm differentiation [7], spermatozoa maturation [8], and other essential functions in development [9,10,11,12,13,14,15]. The mitogen activated protein kinases (MAPK) family pathway is implicated in diverse cellular processes and pathways essential to most organisms. The detailed evolutionary history of the vertebrate MAPK family is largely unclear

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