Role of duplicate genes in robustness against deleterious human mutations.
It is now widely recognized that robustness is an inherent property of biological systems [1],[2],[3]. The contribution of close sequence homologs to genetic robustness against null mutations has been previously demonstrated in simple organisms [4],[5]. In this paper we investigate in detail the contribution of gene duplicates to back-up against deleterious human mutations. Our analysis demonstrates that the functional compensation by close homologs may play an important role in human genetic disease. Genes with a 90% sequence identity homolog are about 3 times less likely to harbor known disease mutations compared to genes with remote homologs. Moreover, close duplicates affect the phenotypic consequences of deleterious mutations by making a decrease in life expectancy significantly less likely. We also demonstrate that similarity of expression profiles across tissues significantly increases the likelihood of functional compensation by homologs.
Hsiao
Tzu-Lin
TL
Center for Computational Biology and Bioinformatics, Columbia University, New York, New York, United States of America.
Vitkup
Dennis
D
D018628:Gene Dosage; D020440:Gene Duplication; D020869:Gene Expression Profiling; D030342:Genetic Diseases, Inborn / Q000235:genetics; D015894:Genome, Human; D006801:Humans; D008957:Models, Genetic; D015233:Models, Statistical; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution