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Biochemical networking contributes more to genetic buffering in human and mouse metabolic pathways than does gene duplication.

Abstract：

:During evolution different genes evolve at unequal rates, reflecting the varying functional constraints on phenotype. An important contributor to this variation is genetic buffering, which reduces the potential detrimental effects of mutations. We studied whether gene duplication and redundant metabolic networks affect genetic buffering by comparing the evolutionary rate of 242 human and mouse orthologous genes involved in metabolic pathways. A gene with a redundant network is defined as one for which the structural layout of metabolic pathways provides an alternative metabolic route that can, in principle, compensate for the loss of a protein function encoded by the gene. We found that genes with redundant networks evolve at similar rates as did genes without redundant networks, [corrected] but no significant difference was detected between single-copy genes and gene families. This implies that redundancy in metabolic networks provides significantly more genetic buffering than do gene families. We also found that genes encoding proteins involved in glycolysis and gluconeogenesis showed as a group a distinct pattern of variation, in contrast to genes involved in other pathways. These results suggest that redundant networks provide genetic buffering and contribute to the functional diversification of metabolic pathways.

journal_name

Nat Genet

journal_title

Nature genetics

authors

Kitami T,Nadeau JH

doi

10.1038/ng945

keywords:

subject

Has Abstract

pub_date

2002-09-01 00:00:00

pages

191-4

issue

1

eissn

1061-4036

issn

1546-1718

pii

ng945

journal_volume

32

pub_type

杂志文章

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