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MBE Advance Access published online on November 10, 2004
Molecular Biology and Evolution, doi:10.1093/molbev/msi045
Molecular Biology and Evolution © Society for Molecular Biology and Evolution 2004; all rights reserved
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Accepted November 2, 2004

Research Article

Inverse Relationship between Evolutionary Rate and Age of Mammalian Genes

M.Mar Albà 1* and Jose Castresana 2

1 Research Group on Biomedical Informatics, Departament de Ciències Experimentals i de la, Salut, Universitat Pompeu Fabra, 08003 Barcelona, Spain
2 Department of Physiology and Molecular Biodiversity, Institut de Biologia Molecular de, Barcelona, CSIC, 08034 Barcelona, Spain

* To whom correspondence should be addressed.
M.Mar Albà, E-mail: malba{at}imim.es


  Abstract

A large proportion of genes is shared by all living organisms while many others are unique to some specific lineages, indicating their different times of origin. The availability of a growing number of eukaryotic genomes allows us to estimate which mammalian genes are novel genes and, approximately, when they arose. In this work we classify human genes in four different age groups and estimate evolutionary rates in human and mouse orthologues. We show that older genes tend to evolve more slowly than newer ones, that is, proteins that arose earlier in evolution currently have a larger proportion of sites subjected to negative selection. Interestingly, this property is maintained when a fraction of the fastest-evolving genes is excluded, or when only genes belonging to a given functional class are considered. One way to explain this relationship is by assuming that genes maintain their functional constraints along all their evolutionary history but that the nature of more recent evolutionary innovations is such that the functional constraints operating on them are increasingly weaker. Alternatively, our results would also be consistent with a scenario where the functional constraints acting on a gene would not need to be constant through evolution. Instead, starting from weak functional constraints near the time of origin of a gene -as supported by mechanisms proposed for the origin of orphan genes- there would be a gradual increase in selective pressures with time, resulting in fewer accepted mutations in older versus more novel genes.

Keywords: novel genes; non-synonymous substitutions; Gene Ontology.
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