Monday, July 09, 2007

Genetic determinants of "evolvability"   posted by p-ter @ 7/09/2007 06:43:00 PM

In comments on previous posts, I've alluded to the "mutational target size" of a phenotype-- that is, the number of locations in the genome that affect (or could, in theory, affect) the phenotype in question. If one imagines mutations as darts thrown randomly at a dartboard, the "target size" analogy is self-explanatory. There are a number of reasons why different phenotypes could have different target sizes-- the number of genes underlying the trait is likely an important parameter, and it seems intuitive to suggest that some phenotypes would be selected for robustness (ie. a smaller target size).

Data in this area is hard to come by. Luckily, expression microarrays have put at our disposition the ability to assay thousands of phenotypes-- gene expression profiles-- in parallel. A recent paper takes a look at this question through the use of mutation accumulation lines in yeast. I've mentioned MA lines before-- essentually, they're lines propogated with an extremely small effective population size, such that selection plays a nearly negligible role in the fate of new mutations.

The authors propogated a number of these lines for 4000 generations, then assayed gene expression to see which genes had diverged in expression, and by how much. The results are somewhat intuitive-- they find that gene expression evolvability is correlated with trans-mutational target size (as judged by expression profiling of knockout strains) and the presence of a particular promoter sequence. This is a small step in out understanding of regulatory evolution, but an important one. They conclude:
We show that not all genes are equally sensitive to the effects of random spontaneous mutations and identify structural properties (presence of a TATA box and trans-mutational target sizes) that greatly influence a gene's potential to undergo regulatory change. These determinants provide a mechanistic basis to serve as a foundation for more-realistic models of gene expression evolution that account for levels of polymorphism and divergence in cis and trans gene regulation.

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