Abstract:
: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.
journal_name
PLoS Genetjournal_title
PLoS geneticsauthors
Hsiao TL,Vitkup Ddoi
10.1371/journal.pgen.1000014subject
Has Abstractpub_date
2008-03-14 00:00:00pages
e1000014issue
3eissn
1553-7390issn
1553-7404journal_volume
4pub_type
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