Null mutations in human and mouse orthologs frequently result in different phenotypes.

ABSTRACT: One-to-one orthologous genes of relatively closely related species are widely assumed to have similar functions and cause similar phenotypes when deleted from the genome. Although this assumption is the foundation of comparative genomics and the basis for the use of model organisms to study human biology and disease, its validity is known only from anecdotes rather than from systematic examination. Comparing documented phenotypes of null mutations in humans and mice, we find that >20% of human essential genes have nonessential mouse orthologs. These changes of gene essentiality appear to be associated with adaptive evolution at the protein-sequence, but not gene-expression, level. Proteins localized to the vacuole, a cellular compartment for waste management, are highly enriched among esse

SUBMITTER: Liao BY 

PROVIDER: S-EPMC2383943 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature