Prediction of pathogenic mutations in mitochondrially encoded human tRNAs Journal Article

Author(s): Kondrashov, Fyodor A
Article Title: Prediction of pathogenic mutations in mitochondrially encoded human tRNAs
Abstract: Some mutations in human mitochondrial tRNAs are severely pathogenic. The available computational methods have a poor record of predicting the impact of a tRNA mutation on the phenotype and fitness. Here patterns of evolution at tRNA sites that harbor pathogenic mutations and at sites that harbor phenotypically cryptic polymorphisms were compared. Mutations that are pathogenic to humans occupy more conservative sites, are only rarely fixed in closely related species, and, when located in stem structures, often disrupt Watson-Crick pairing and display signs of compensatory evolution. These observations make it possible to classify ∼90% of all known pathogenic mutations as deleterious together with only ∼30% of polymorphisms. These polymorphisms segregate at frequencies that are more than two times lower than frequencies of polymorphisms classified as benign, indicating that at least ∼30% of known polymorphisms in mitochondrial tRNAs affect fitness negatively.
Journal Title: Human Molecular Genetics
Volume: 14
Issue 16
ISSN: 0964-6906
Publisher: Oxford University Press  
Date Published: 2005-08-15
Start Page: 2415
End Page: 2419
DOI: 10.1093/hmg/ddi243
Notes: The author thanks P. Andolfatto, D. Bachtrog, N. Esipova, S. Makeev, A. Kondrashov, V. Ramensky, V. Tumanyan and P. Vlasov for a critical reading of the manuscript. The author is an NSF Graduate Research Fellow. This work was supported by a Contract of the Russian Ministry of Science and Education (02.434.11.1008) and a grant on Molecular and Cellular Biology from RAS.
Open access: no