Abstract
There is increasing evidence in eukaryotic genomes that gene order is not random, even allowing for tandem duplication. Notably, in numerous genomes1,2,3,4,5,6, genes of similar expression tend to be clustered. Are there other reasons for clustering of functionally similar genes? If genes are linked to enable genetic, rather than physical clustering, then we also expect that clusters of certain genes might be associated with blocks of reduced recombination rates. Here we show that, in yeast, essential genes are highly clustered and this clustering is independent of clustering of co-expressed genes and of tandem duplications. Adjacent pairs of essential genes are preferentially conserved through evolution. Notably, we also find that clusters of essential genes are in regions of low recombination and that larger clusters have lower recombination rates. These results suggest that selection acts to modify both the fine-scale intragenomic variation in the recombination rate and the distribution of genes and provide evidence for co-evolution of gene order and recombination rate.
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References
Cohen, B.A., Mitra, R.D., Hughes, J.D. & Church, G.M. A computational analysis of whole-genome expression data reveals chromosomal domains of gene expression. Nat. Genet. 26, 183–186 (2000).
Lercher, M.J., Urrutia, A.O. & Hurst, L.D. Clustering of housekeeping genes provides a unified model of gene order in the human genome. Nat. Genet. 31, 180–183 (2002).
Blumenthal, T. et al. A global analysis of Caenorhabditis elegans operons. Nature 417, 851–854 (2002).
Spellman, P.T. & Rubin, G.M. Evidence for large domains of similarly expressed genes in the Drosophila genome. J. Biol. 1, 5 (2002).
Lercher, M.J., Blumenthal, T. & Hurst, L.D. Co-expression of neighbouring genes in Caenorhabditis elegans is mostly due to operons and duplicate genes. Genome Res. (in the press).
Florens, L. et al. A proteomic view of the Plasmodium falciparum life cycle. Nature 419, 520–526 (2002).
Seoighe, C. et al. Prevalence of small inversions in yeast gene order evolution. Proc. Natl. Acad. Sci. USA 97, 14433–14437 (2000).
Hurst, L.D., Williams, E.J. & Pal, C. Natural selection promotes the conservation of linkage of co-expressed genes. Trends Genet. 18, 604–606 (2002).
Nei, M. Evolutionary change in linkage intensity. Nature 218, 1160–1161 (1968).
Gerton, J.L. et al. Inaugural article: global mapping of meiotic recombination hotspots and coldspots in the yeast Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 97, 11383–11390 (2000).
Nei, M. Modification of linkage intensity by natural selection. Genetics 57, 625–641 (1967).
Jeffreys, A.J., Kauppi, L. & Neumann, R. Intensely punctate meiotic recombination in the class II region of the major histocompatibility complex. Nat. Genet. 29, 217–222 (2001).
Strathern, J.N., Shafer, B.K. & McGill, C.B. DNA-synthesis errors associated with double-strand-break repair. Genetics 140, 965–972 (1995).
Cox, E.C. On the organization of higher chromosomes. Nature 92, 133–134 (1972).
Hirsh, A.E. & Fraser, H.B. Protein dispensability and rate of evolution. Nature 411, 1046–1049 (2001).
Gessler, D.D. & Xu, S. On the evolution of recombination and meiosis. Genet. Res. 73, 119–131 (1999).
Strathern, J.N., Jones, E.W. & Broach, J.R. The molecular biology of the yeast Saccharomyces life cycle and inheritance. (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 1981).
Dickinson, J.R. & Schweizer, M. The metabolism and molecular physiology of Saccharomyces cerevisiae. (Taylor and Francis, London, 1999).
Mortimer, R.K., Romano, P., Suzzi, G. & Polsinelli, M. Genome renewal: a new phenomenon revealed from a genetic study of 43 strains of Saccharomyces cerevisiae derived from natural fermentation of grape musts. Yeast 10, 1543–1552 (1994).
Cooper, D.N. Human Gene Evolution (BIOS Scientific Publishers Limited, Oxford, UK, 1999).
Fraser, A.G. et al. Functional genomic analysis of C. elegans chromosome I by systematic RNA interference. Nature 408, 325–330 (2000).
Ball, C.A. et al. Saccharomyces Genome Database provides tools to survey gene expression and functional analysis data. Nucleic Acids Res. 29, 80–81 (2001).
Costanzo, M.C. et al. YPD, PombePD and WormPD: model organism volumes of the BioKnowledge library, an integrated resource for protein information. Nucleic Acids Res. 29, 75–79 (2001).
Stein, L., Sternberg, P., Durbin, R., Thierry-Mieg, J. & Spieth, J. WormBase: network access to the genome and biology of Caenorhabditis elegans. Nucleic Acids Res. 29, 82–86 (2001).
Winzeler, E.A. et al. Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science 285, 901–906 (1999).
Marais, G., Mouchiroud, D. & Duret, L. Does recombination improve selection on codon usage? Lessons from nematode and fly complete genomes. Proc. Natl. Acad. Sci. USA 98, 5688–5692 (2001).
Steinmetz, L.M. et al. Systematic screen for human disease genes in yeast. Nat. Genet. 31, 400–404 (2002).
Altschul, S.F. et al. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 25, 3389–3402 (1997).
Acknowledgements
We would like to thank F. Kondrashov and B. Papp for comments on an earlier version of the manuscript. C.P is funded by a Royal Society/Nato visiting fellowship and L.D.H. by the UK Biotechnology and Biosciences Research Council.
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Pál, C., Hurst, L. Evidence for co-evolution of gene order and recombination rate. Nat Genet 33, 392–395 (2003). https://doi.org/10.1038/ng1111
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DOI: https://doi.org/10.1038/ng1111
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