Compensated pathogenic deviations
Deleterious or ‘disease-associated’ mutations are mutations that lead to disease with high phenotype penetrance: they are inherited in a simple Mendelian manner, or, in the case of cancer, accumulate in somatic cells leading directly to disease. However, in some cases, the amino acid that is substit...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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De Gruyter
2011-08-01
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| Series: | Biomolecular Concepts |
| Subjects: | |
| Online Access: | https://doi.org/10.1515/bmc.2011.025 |
| _version_ | 1818587163906801664 |
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| author | Barešić Anja Martin Andrew C.R. |
| author_facet | Barešić Anja Martin Andrew C.R. |
| author_sort | Barešić Anja |
| collection | DOAJ |
| description | Deleterious or ‘disease-associated’ mutations are mutations that lead to disease with high phenotype penetrance: they are inherited in a simple Mendelian manner, or, in the case of cancer, accumulate in somatic cells leading directly to disease. However, in some cases, the amino acid that is substituted resulting in disease is the wild-type native residue in the functionally equivalent protein in another species. Such examples are known as ‘compensated pathogenic deviations’ (CPDs) because, somewhere in the second species, there must be compensatory mutations that allow the protein to function normally despite having a residue which would cause disease in the first species. Depending on the nature of the mutations, compensation can occur in the same protein, or in a different protein with which it interacts. In principle, compensation can be achieved by a single mutation (most probably structurally close to the CPD), or by the cumulative effect of several mutations. Although it is clear that these effects occur in proteins, compensatory mutations are also important in RNA potentially having an impact on disease. As a much simpler molecule, RNA provides an interesting model for understanding mechanisms of compensatory effects, both by looking at naturally occurring RNA molecules and as a means of computational simulation. This review surveys the rather limited literature that has explored these effects. Understanding the nature of CPDs is important in understanding traversal along fitness landscape valleys in evolution. It could also have applications in treating diseases that result from such mutations. |
| first_indexed | 2024-12-16T09:04:30Z |
| format | Article |
| id | doaj.art-24bcaa2fcb8c448fba3b53279b4739e4 |
| institution | Directory Open Access Journal |
| issn | 1868-5021 1868-503X |
| language | English |
| last_indexed | 2024-12-16T09:04:30Z |
| publishDate | 2011-08-01 |
| publisher | De Gruyter |
| record_format | Article |
| series | Biomolecular Concepts |
| spelling | doaj.art-24bcaa2fcb8c448fba3b53279b4739e42022-12-21T22:37:05ZengDe GruyterBiomolecular Concepts1868-50211868-503X2011-08-012428129210.1515/bmc.2011.025Compensated pathogenic deviationsBarešić Anja0Martin Andrew C.R.1Institute of Structural and Molecular Biology, Division of Biosciences, University College London, Darwin Building, Gower Street, London WC1E 6BT, UKInstitute of Structural and Molecular Biology, Division of Biosciences, University College London, Darwin Building, Gower Street, London WC1E 6BT, UKDeleterious or ‘disease-associated’ mutations are mutations that lead to disease with high phenotype penetrance: they are inherited in a simple Mendelian manner, or, in the case of cancer, accumulate in somatic cells leading directly to disease. However, in some cases, the amino acid that is substituted resulting in disease is the wild-type native residue in the functionally equivalent protein in another species. Such examples are known as ‘compensated pathogenic deviations’ (CPDs) because, somewhere in the second species, there must be compensatory mutations that allow the protein to function normally despite having a residue which would cause disease in the first species. Depending on the nature of the mutations, compensation can occur in the same protein, or in a different protein with which it interacts. In principle, compensation can be achieved by a single mutation (most probably structurally close to the CPD), or by the cumulative effect of several mutations. Although it is clear that these effects occur in proteins, compensatory mutations are also important in RNA potentially having an impact on disease. As a much simpler molecule, RNA provides an interesting model for understanding mechanisms of compensatory effects, both by looking at naturally occurring RNA molecules and as a means of computational simulation. This review surveys the rather limited literature that has explored these effects. Understanding the nature of CPDs is important in understanding traversal along fitness landscape valleys in evolution. It could also have applications in treating diseases that result from such mutations.https://doi.org/10.1515/bmc.2011.025co-adaptationco-evolutiondeleterious mutationsdisease-associated mutationsepistasissingle nucleotide polymorphisms |
| spellingShingle | Barešić Anja Martin Andrew C.R. Compensated pathogenic deviations Biomolecular Concepts co-adaptation co-evolution deleterious mutations disease-associated mutations epistasis single nucleotide polymorphisms |
| title | Compensated pathogenic deviations |
| title_full | Compensated pathogenic deviations |
| title_fullStr | Compensated pathogenic deviations |
| title_full_unstemmed | Compensated pathogenic deviations |
| title_short | Compensated pathogenic deviations |
| title_sort | compensated pathogenic deviations |
| topic | co-adaptation co-evolution deleterious mutations disease-associated mutations epistasis single nucleotide polymorphisms |
| url | https://doi.org/10.1515/bmc.2011.025 |
| work_keys_str_mv | AT baresicanja compensatedpathogenicdeviations AT martinandrewcr compensatedpathogenicdeviations |