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Characterization of the definitive classical calpain family of vertebrates using phylogenetic, evolutionary and expression analyses.

Macqueen DJ, Wilcox AH - Open Biol (2014)

Bottom Line: We reveal that while all vertebrate classical calpains have been subject to persistent purifying selection during evolution, the degree and nature of selective pressure has often been lineage-dependent.This highlighted systematic divergence in expression across vertebrate taxa, with most classic calpain genes from fish and amphibians having more extensive tissue distribution than in amniotes.Our data suggest that classical calpain functions have frequently diverged during vertebrate evolution and challenge the ongoing value of the established system of classifying calpains by expression.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biological and Environmental Sciences, University of Aberdeen, Tillydrone Avenue, Aberdeen AB24 2TZ, UK.

ABSTRACT
The calpains are a superfamily of proteases with extensive relevance to human health and welfare. Vast research attention is given to the vertebrate 'classical' subfamily, making it surprising that the evolutionary origins, distribution and relationships of these genes is poorly characterized. Consequently, there exists uncertainty about the conservation of gene family structure, function and expression that has been principally defined from work with mammals. Here, more than 200 vertebrate classical calpains were incorporated in phylogenetic analyses spanning an unprecedented range of taxa, including jawless and cartilaginous fish. We demonstrate that the common vertebrate ancestor had at least six classical calpains, including a single gene that gave rise to CAPN11, 1, 2 and 8 in the early jawed fish lineage, plus CAPN3, 9, 12, 13 and a novel calpain gene, hereafter named CAPN17. We reveal that while all vertebrate classical calpains have been subject to persistent purifying selection during evolution, the degree and nature of selective pressure has often been lineage-dependent. The tissue expression of the complete classic calpain family was assessed in representative teleost fish, amphibians, reptiles and mammals. This highlighted systematic divergence in expression across vertebrate taxa, with most classic calpain genes from fish and amphibians having more extensive tissue distribution than in amniotes. Our data suggest that classical calpain functions have frequently diverged during vertebrate evolution and challenge the ongoing value of the established system of classifying calpains by expression.

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Reconstruction of selective constraints acting on classical calpains ancestral to jawed vertebrates. Different calpain family members are labelled (a)–(i) in ranked order by the overall strength of purifying selection acting during evolution. For each calpain, an empirical phylogeny is provided with the branches coloured according to five dN/dS ranges: dark blue is 0–0.2; marine blue is 0.2–0.4; yellow is 0.4–1.0; red is >1.0; grey branches, dS saturated. Summary statistics are shown including dN/dS means (x̄), standard deviation (s.d.) and coefficient of variation (COV).
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RSOB130219F4: Reconstruction of selective constraints acting on classical calpains ancestral to jawed vertebrates. Different calpain family members are labelled (a)–(i) in ranked order by the overall strength of purifying selection acting during evolution. For each calpain, an empirical phylogeny is provided with the branches coloured according to five dN/dS ranges: dark blue is 0–0.2; marine blue is 0.2–0.4; yellow is 0.4–1.0; red is >1.0; grey branches, dS saturated. Summary statistics are shown including dN/dS means (x̄), standard deviation (s.d.) and coefficient of variation (COV).

Mentions: To gain insights into how natural selection has acted on different classical calpains, we established dN/dS ratios at every branch in phylogenetic trees for family members ancestral to jawed vertebrates (figure 4). Purifying selection, i.e. selection to remove deleterious changes in protein sequence, has been the predominant force for all the classic calpains, with branch-averaged dN/dS values ranging from 0.11 to 0.37 (figure 4a–i).Figure 4.


Characterization of the definitive classical calpain family of vertebrates using phylogenetic, evolutionary and expression analyses.

Macqueen DJ, Wilcox AH - Open Biol (2014)

Reconstruction of selective constraints acting on classical calpains ancestral to jawed vertebrates. Different calpain family members are labelled (a)–(i) in ranked order by the overall strength of purifying selection acting during evolution. For each calpain, an empirical phylogeny is provided with the branches coloured according to five dN/dS ranges: dark blue is 0–0.2; marine blue is 0.2–0.4; yellow is 0.4–1.0; red is >1.0; grey branches, dS saturated. Summary statistics are shown including dN/dS means (x̄), standard deviation (s.d.) and coefficient of variation (COV).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4043111&req=5

RSOB130219F4: Reconstruction of selective constraints acting on classical calpains ancestral to jawed vertebrates. Different calpain family members are labelled (a)–(i) in ranked order by the overall strength of purifying selection acting during evolution. For each calpain, an empirical phylogeny is provided with the branches coloured according to five dN/dS ranges: dark blue is 0–0.2; marine blue is 0.2–0.4; yellow is 0.4–1.0; red is >1.0; grey branches, dS saturated. Summary statistics are shown including dN/dS means (x̄), standard deviation (s.d.) and coefficient of variation (COV).
Mentions: To gain insights into how natural selection has acted on different classical calpains, we established dN/dS ratios at every branch in phylogenetic trees for family members ancestral to jawed vertebrates (figure 4). Purifying selection, i.e. selection to remove deleterious changes in protein sequence, has been the predominant force for all the classic calpains, with branch-averaged dN/dS values ranging from 0.11 to 0.37 (figure 4a–i).Figure 4.

Bottom Line: We reveal that while all vertebrate classical calpains have been subject to persistent purifying selection during evolution, the degree and nature of selective pressure has often been lineage-dependent.This highlighted systematic divergence in expression across vertebrate taxa, with most classic calpain genes from fish and amphibians having more extensive tissue distribution than in amniotes.Our data suggest that classical calpain functions have frequently diverged during vertebrate evolution and challenge the ongoing value of the established system of classifying calpains by expression.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biological and Environmental Sciences, University of Aberdeen, Tillydrone Avenue, Aberdeen AB24 2TZ, UK.

ABSTRACT
The calpains are a superfamily of proteases with extensive relevance to human health and welfare. Vast research attention is given to the vertebrate 'classical' subfamily, making it surprising that the evolutionary origins, distribution and relationships of these genes is poorly characterized. Consequently, there exists uncertainty about the conservation of gene family structure, function and expression that has been principally defined from work with mammals. Here, more than 200 vertebrate classical calpains were incorporated in phylogenetic analyses spanning an unprecedented range of taxa, including jawless and cartilaginous fish. We demonstrate that the common vertebrate ancestor had at least six classical calpains, including a single gene that gave rise to CAPN11, 1, 2 and 8 in the early jawed fish lineage, plus CAPN3, 9, 12, 13 and a novel calpain gene, hereafter named CAPN17. We reveal that while all vertebrate classical calpains have been subject to persistent purifying selection during evolution, the degree and nature of selective pressure has often been lineage-dependent. The tissue expression of the complete classic calpain family was assessed in representative teleost fish, amphibians, reptiles and mammals. This highlighted systematic divergence in expression across vertebrate taxa, with most classic calpain genes from fish and amphibians having more extensive tissue distribution than in amniotes. Our data suggest that classical calpain functions have frequently diverged during vertebrate evolution and challenge the ongoing value of the established system of classifying calpains by expression.

Show MeSH