DOI:10.1038/nrg2153

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Some traits are more evolvable than others — mutations in the underlying genes are more likely to have phe-notypic consequences. A new study looks at what structural features and regulatory interactions of a gene gov-ern the sensitivity of transcriptional phenotypes to mutations.

Looking at natural variation within or between species does not provide an unbiased survey of the effects of mutations, because in these settings most mutations are filtered out by natural selec-tion. Instead, Landry, Lemos and colleagues produced a series of yeast mutation-accumulation lines derived from a common ancestor, each of which was maintained with a small effective population size to ensure that the fate of mutations was the result of genetic drift rather than selection. They chose four of these lines at random and used micro-arrays to assess their gene-expression levels.

The authors found 2,031 genes that were differentially expressed between lines, and for each they calculated the amount of variation in expression caused by mutation. This mutational variance correlated with the trans-mutational target size

of the gene — the number of other genes whose activity affects it — and also the cis-mutational target size — the number of different regulatory sites that are associated with the gene. This implies that those genes that are involved in more network interactions are more sensitive to mutations and are therefore more evolvable. Indeed, the authors also showed that genes with high muta-tional variance tend to be the ones that have high variation in expression between natural populations. They also looked specifically at genes with TATA boxes, as these are often associated with adaptive divergence in experimental evolution and with between-species divergence, and found that they have elevated mutational variance.

Interestingly, the sensitivity of gene-expression levels to mutational perturbation correlated with sensitiv-ity to environmental perturbation and transcriptional noise. This shows that understanding the properties of genetic networks, such as robustness, will be important for understanding phenotypic evolution. Studies such as this are an important step in this direction.

Patrick Goymer

ORIGINAL RESEARCH PAPER Landry, C. R. & Lemos, B. et al. Genetic properties influencing the evolvability of gene expression. Science 24 May 2007 (doi:10.1126/science.1140247)FURTHER READING Boone, C., Bussey, H. & Andrews, B. J. Exploring genetic interactions and networks with yeast. Nature Rev. Genet. 8, 437–449 (2007)

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Interacting genes are more evolvable

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NATURE REVIEWS | GENETICS VOLUME 8 | JULY 2007

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