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. 2011;6(10):e26999.
doi: 10.1371/journal.pone.0026999. Epub 2011 Oct 26.

Evolutionary history of the vertebrate mitogen activated protein kinases family

Meng Li  1 , Jun Liu, Chiyu Zhang
Affiliations

Evolutionary history of the vertebrate mitogen activated protein kinases family

Meng Li et al. PLoS One. 2011.

Abstract

Background: The 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 findings: The 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/significance: These results provide valuable insight into the evolutionary history of the vertebrate MAPK family.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Maximum likelihood (ML) phylogenetic tree of the vertebrate MAPK family.
The ML tree was constructed based on the protein sequences of the MAPK family using PHYML v2.4 with 100 bootstrap replications. The tree is unrooted and only the bootstrap values >70% are shown at interior nodes. The MAPK protein sequences from mammals, amphibians/reptiles and teleosts are marked in blue, green and red, respectively. The scale bar indicates the branch length that corresponds to 0.2 substitutions per site. The species and accession numbers are listed in Table S1. The corresponding amino acid sequence alignment is provided in Figure S2. The abbreviations used are as follows: Hsa, Homo sapiens; Mamu, Macaca mulatta; Ptr, Pan troglodytes; Mumu, Mus musculus; Rno, Rattus norvegicus; Oan, Ornithorhynchus anatinus; Mdo, Monodelphis domestica; Bta, Bos taurus; Clu, Canis lupus familiaris; Eca, Equus caballus; Oar, Ovis aries; Ssc, Sus scrofa; Dre, Danio rerio; Gga, Gallus gallus; Tgu, Taeniopygia guttata; Gac, Gasterosteus aculeatus; Orl, Oryzias latipes; Tru, Takifugu rubripes; Tni, Tetraodon nigroviridis; Aca, Anolis carolinensis; Xtr, Xenopus tropicalis; Ttr, Tursiops truncatus; Cin, Ciona intestinalis; Csa, Ciona savignyi; Spu, Strongylocentrotus purpuratus.
Figure 2
Figure 2. Bayesian phylogenetic tree of the MAPK protein sequences from vertebrates, tunicates, echinoderm, nematodes, arthropods and plants.
The red stars indicate 3 earlier progenitors of the MAPK family. The tree is unrooted and Bayesian posterior probability values (>70%) are shown at interior nodes. The scale bar corresponds to 0.1 substitutions per site. The branches that correspond to vertebrates, echinoderm and tunicates, nematodes, arthropods, and plants are marked in black, red, green, blue, and purple, respectively. The species and accession numbers are listed in Table S1. The corresponding amino acid sequence alignment is provided in Figure S3. The abbreviations used are as follows: Isc, Ixodes scapularis; Aae, Aedes aegypti; Ame, Apis mellifera; Dme, Drosophila melanogaster; Api, Acyrthosiphon pisum; Cbr, Caenorhabditis brenneri; Cre, Caenorhabditis remanei; Cel, Caenorhabditis elegans.
Figure 3
Figure 3. Order and orientation of genes syntenic to (A): MAPK11 and MAPK12, (B): MAPK13 and MAPK14, and (C): MAPK7.
Genes are intentionally aligned in columns to facilitate visualization of synteny. For other details, please see text.
Figure 4
Figure 4. Exon numbers of the vertebrate MAPK subfamilies.
The average exon numbers of 13 vertebrate MAPK subfamilies are shown in panel (A). The comparisons of MAPK4, MAPK7, and MAPK6 with their flanking genes in average exon numbers are shown in panels (B), (C), and (D), respectively. In panel (B), only MAPK4 and its right-flanking (ME2) genes were taken into account due to a difference of its left-flanking genes between teleosts and amphibians (Figure S4), and in panel (D), only MAPK6 and its left-flanking (LEO1) genes were taken into account due to a difference of its right-flanking genes between teleosts and amphibians (Figure S4). In panel (C), only MAPK7 and its left-flanking (MFAP4) genes from amphibians and mammals were taken into account due to differences of both its left- and right-flanking genes between teleosts and other taxa, and of its right-flanking genes between amphibians and mammals (Figure 3). One asterisk indicates P<0.05 and two asterisks P<0.01 (one-way ANOVA followed by the Bonferroni test).
Figure 5
Figure 5. Pairwise comparison plots of dN and dS values for each MAPK subfamily.
The dN and dS values were calculated with MEGA4.0. The transition/transversion ratios used for each subfamily are: MAPK1: 2.398; MAPK3: 4.008; MAPK4: 1.428; MAPK6: 2.183; MAPK7: 1.167; MAPK8: 1.132; MAPK9: 1.745; MAPK10: 2.126; MAPK11: 1.706; MAPK12: 1.552; MAPK13: 0.809; MAPK14: 1.803; MAPK15: 1.361.
Figure 6
Figure 6. Motif distributions of the 13 vertebrate MAPK subfamiles.
The protein kinase domains are drawn as grey boxes. The motifs lost in teleosts are drawn as blue and other motifs as green. The LXXLL1-LXXLL2 motifs are marked in purple. The motifs, especially the protein kinase domains, are not drawn to scale. The sequences of these motifs are given in Table S3.
Figure 7
Figure 7. Sequence logos of some specific motifs identified in this study.
(A), the motifs shared by at least two vertebrate MAPK subfamilies. (B), the motifs specially found in higher vertebrate taxa. The character and size of each logo represent the proportion of an amino acid at the specific site. The sequence logos were generated by the web-based program WEBLOGO 3. The sequence logos of other motifs are shown in Figure S6.
See this image and copyright information in PMC

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