ArticleMolecular biology and evolution2014
Positive selection during the evolution of the blood coagulation factors in the context of their disease-causing mutations.
Article in Molecular biology and evolution, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 27 citations in OpenAlex.
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- Genome-Wide DNA Methylation Profile Indicates Potential Epigenetic Regulation of Aging in the Rhesus Macaque Thymus.International journal of molecular sciences · 2022Article
- Genetic duplication of tissue factor reveals subfunctionalization in venous and arterial hemostasis.PLoS genetics · 2022Article
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- Standardization of Coagulation Factor V Reference Intervals, Prothrombin Time, and Activated Partial Thromboplastin Time in Mice for Use in Factor V Deficiency Pathological Models.Frontiers in veterinary science · 2022Article
- High Mutational Heterogeneity, and New Mutations in the Human Coagulation Factor V Gene. Future Perspectives for Factor V Deficiency Using Recombinant and Advanced Therapies.International journal of molecular sciences · 2021Article
- Molecular mechanisms of growth depression in broiler chickens (Gallus Gallus domesticus) mediated by immune stress: a hepatic proteome study.Journal of animal science and biotechnology · 2021Article
- Genome-wide ancestry and introgression in a Zambian baboon hybrid zone.Molecular ecology · 2021Article
- Chromosome X-wide Analysis of Positive Selection in Human Populations: Common and Private Signals of Selection and its Impact on Inactivated Genes and Enhancers.Frontiers in genetics · 2021Article
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- Statistical Validation of Rare Complement Variants Provides Insights into the Molecular Basis of Atypical Hemolytic Uremic Syndrome and C3 Glomerulopathy.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- The phenotypic legacy of admixture between modern humans and Neandertals.Science (New York, N.Y.) · 2016Article
- Evolutionary insights into host-pathogen interactions from mammalian sequence data.Nature reviews. Genetics · 2015Review
- New functional and structural insights from updated mutational databases for complement factor H, Factor I, membrane cofactor protein and C3.Bioscience reports · 2014Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Blood coagulation occurs through a cascade of enzymes and cofactors that produces a fibrin clot, while otherwise maintaining hemostasis. The 11 human coagulation factors (FG, FII-FXIII) have been identified across all vertebrates, suggesting that they emerged with the first vertebrates around 500 Ma. Human FVIII, FIX, and FXI are associated with thousands of disease-causing mutations. Here, we evaluated the strength of selective pressures on the 14 genes coding for the 11 factors during vertebrate evolution, and compared these with human mutations in FVIII, FIX, and FXI. Positive selection was identified for fibrinogen (FG), FIII, FVIII, FIX, and FX in the mammalian Primates and Laurasiatheria and the Sauropsida (reptiles and birds). This showed that the coagulation system in vertebrates was under strong selective pressures, perhaps to adapt against blood-invading pathogens. The comparison of these results with disease-causing mutations reported in FVIII, FIX, and FXI showed that the number of disease-causing mutations, and the probability of positive selection were inversely related to each other. 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. This improved understanding of evolutionary changes in FVIII, FIX, and FXI provided greater insight into disease-causing mutations, and better assessments of the codon sites that may be mutated in applications of gene therapy.
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