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

Nature Genetics volume 32, pages 191–194 (2002)Cite this article

A Corrigendum to this article was published on 01 December 2002

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 evolved more quickly than did genes without redundant networks, 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.

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Figure 1: Distribution of Ka/Ks values for 242 genes encoding proteins in various metabolic pathways.
Figure 2: Schematic for defining networks on the basis of the structure of metabolic pathways.

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Acknowledgements

We thank E. Eichler and S. Rutherford for comments on a draft of this manuscript and J. Bailey and M. Johnson for assistance with the computational analysis. This work was supported by a grant from the US National Institutes of Health and a gift from the Charles B. Wang Foundation.

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Authors and Affiliations

  1. Department of Genetics, Case Western Reserve University, Cleveland, 44106, Ohio, USA

    Toshimori Kitami & Joseph H. Nadeau

  2. Center for Computational Genomics, Case Western Reserve University, Cleveland, 44106, Ohio, USA

    Toshimori Kitami & Joseph H. Nadeau

  3. Center for Human Genetics, University Hospitals of Cleveland, Cleveland, 44106, Ohio, USA

    Toshimori Kitami & Joseph H. Nadeau

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  1. Toshimori Kitami
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  2. Joseph H. Nadeau
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Correspondence to Joseph H. Nadeau.

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Kitami, T., Nadeau, J. Biochemical networking contributes more to genetic buffering in human and mouse metabolic pathways than does gene duplication. Nat Genet 32, 191–194 (2002). https://doi.org/10.1038/ng945

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