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Positive selection during the evolution of the blood coagulation factors in the context of their disease-causing mutations.

Rallapalli PM, Orengo CA, Studer RA, Perkins SJ - Mol. Biol. Evol. (2014)

Bottom Line: It was concluded that when a site was under positive selection, it was less likely to be associated with disease-causing mutations.In contrast, sites under negative selection were more likely to be associated with disease-causing mutations and be destabilizing.A residue-by-residue comparison of the FVIII, FIX, and FXI sequence alignments confirmed this.

View Article: PubMed Central - PubMed

Affiliation: Department of Structural and Molecular Biology, University College London, London, United Kingdom.

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Positively selected genes of the coagulation cascade in vertebrates, mammals, and three major clades. The layout of this figure is a simplified representation of figure 1. Genes showing significant positive selection in the LRT calculations are highlighted in red. (a) Positive selection was observed in five genes when all 47 genome sequences (vertebrates) were analyzed as a single group. (b) In the Mammals group (fig. 2), where positive selection is seen for five genes, only the (c) Primates and (d) Laurasiatheria clades are shown with positive selection for two or three genes only, because no positive selection was seen in the Glires clade whereas insufficient sequences were available in the Atlantogenata clade for conclusions to be drawn. (e) Positive selection was seen in the Sauropsida, clade but no positive selection was observed in Fishes (fig. 2).
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msu248-F3: Positively selected genes of the coagulation cascade in vertebrates, mammals, and three major clades. The layout of this figure is a simplified representation of figure 1. Genes showing significant positive selection in the LRT calculations are highlighted in red. (a) Positive selection was observed in five genes when all 47 genome sequences (vertebrates) were analyzed as a single group. (b) In the Mammals group (fig. 2), where positive selection is seen for five genes, only the (c) Primates and (d) Laurasiatheria clades are shown with positive selection for two or three genes only, because no positive selection was seen in the Glires clade whereas insufficient sequences were available in the Atlantogenata clade for conclusions to be drawn. (e) Positive selection was seen in the Sauropsida, clade but no positive selection was observed in Fishes (fig. 2).

Mentions: The overall picture is that a total of nine coagulation factor proteins (out of the 11 of the cascade) underwent positive selection at one or more stages in evolution (fig. 3). The highest number of genes under positive selection within an individual clade is five (for vertebrates and mammals). For Vertebrates, using the LRT M8a-M8, positive selection was found in as many as five of the 14 coagulation genes (table 2). In figure 3a, these included F2, F5, F7, F10, and F13A for all 47 vertebrates. In figure 3b, these included FGA, F3, F5, F8, and F9 for the 30 mammals. In figure 3c–e, these included FGB, F5, and F8 (Primates); FGA and F13B (Laurasiatheria), and F3 (Sauropsida). FG (FG = FGA + FGB + FGG) and F5 were observed to undergo the most extensive positive selection compared with any other coagulation genes. The selective pressure on all the genes in different clades was identified from the LRT values (table 2), except for those of F11 in Laurasiatheria, Sauropsida, and Fishes, F12 in Sauropsida and Fishes, and F13B in Fishes because these genes were absent (supplementary table S1, Supplementary Material online).Fig. 3.


Positive selection during the evolution of the blood coagulation factors in the context of their disease-causing mutations.

Rallapalli PM, Orengo CA, Studer RA, Perkins SJ - Mol. Biol. Evol. (2014)

Positively selected genes of the coagulation cascade in vertebrates, mammals, and three major clades. The layout of this figure is a simplified representation of figure 1. Genes showing significant positive selection in the LRT calculations are highlighted in red. (a) Positive selection was observed in five genes when all 47 genome sequences (vertebrates) were analyzed as a single group. (b) In the Mammals group (fig. 2), where positive selection is seen for five genes, only the (c) Primates and (d) Laurasiatheria clades are shown with positive selection for two or three genes only, because no positive selection was seen in the Glires clade whereas insufficient sequences were available in the Atlantogenata clade for conclusions to be drawn. (e) Positive selection was seen in the Sauropsida, clade but no positive selection was observed in Fishes (fig. 2).
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msu248-F3: Positively selected genes of the coagulation cascade in vertebrates, mammals, and three major clades. The layout of this figure is a simplified representation of figure 1. Genes showing significant positive selection in the LRT calculations are highlighted in red. (a) Positive selection was observed in five genes when all 47 genome sequences (vertebrates) were analyzed as a single group. (b) In the Mammals group (fig. 2), where positive selection is seen for five genes, only the (c) Primates and (d) Laurasiatheria clades are shown with positive selection for two or three genes only, because no positive selection was seen in the Glires clade whereas insufficient sequences were available in the Atlantogenata clade for conclusions to be drawn. (e) Positive selection was seen in the Sauropsida, clade but no positive selection was observed in Fishes (fig. 2).
Mentions: The overall picture is that a total of nine coagulation factor proteins (out of the 11 of the cascade) underwent positive selection at one or more stages in evolution (fig. 3). The highest number of genes under positive selection within an individual clade is five (for vertebrates and mammals). For Vertebrates, using the LRT M8a-M8, positive selection was found in as many as five of the 14 coagulation genes (table 2). In figure 3a, these included F2, F5, F7, F10, and F13A for all 47 vertebrates. In figure 3b, these included FGA, F3, F5, F8, and F9 for the 30 mammals. In figure 3c–e, these included FGB, F5, and F8 (Primates); FGA and F13B (Laurasiatheria), and F3 (Sauropsida). FG (FG = FGA + FGB + FGG) and F5 were observed to undergo the most extensive positive selection compared with any other coagulation genes. The selective pressure on all the genes in different clades was identified from the LRT values (table 2), except for those of F11 in Laurasiatheria, Sauropsida, and Fishes, F12 in Sauropsida and Fishes, and F13B in Fishes because these genes were absent (supplementary table S1, Supplementary Material online).Fig. 3.

Bottom Line: It was concluded that when a site was under positive selection, it was less likely to be associated with disease-causing mutations.In contrast, sites under negative selection were more likely to be associated with disease-causing mutations and be destabilizing.A residue-by-residue comparison of the FVIII, FIX, and FXI sequence alignments confirmed this.

View Article: PubMed Central - PubMed

Affiliation: Department of Structural and Molecular Biology, University College London, London, United Kingdom.

Show MeSH