cis versus trans effects - senecio7の日記

Pennisi E 2008 Deciphering the genetics of evolution. Science 321:760-763.

early suggestions that gene regulation could be important to evolution came in the 1970s from work by bacterial geneticists showing a link between gene expression and enzyme activity in bacteria
about the same time, Allan Wilson and Mary-Claire King of the University of California, Berkeley, concluded that genes and proteins of chimps and humans are so similar that our bipedal, hairless existence must be the product of changes in when, where, and to what degree those genes and proteins come into play
the tools to track down the molecular controls on gene expression and protein production didn't yet exist

David Stern, a Princeton University evolutionary biologist, was probing the genetic changes that result in hairless fruit fly larvae
in 2000, Stern found that mutations in genes were not involved and that changes in the regulation of a gene called shavenbaby were the cause
Sean Carroll of the University of Wisconsin (UW), Madison, saw a similar pattern in his group's studies of pigmentation patterns in fruit flies and in 2005 wrote an influential paper in PLoS Biology that helped convince the field that cis-regulatory changes were central to morphological evolution
genes involved in establishing body plans and patterns have such a broad reach
affecting a variety of tissues at multiple stages of development
mutations in their coding regions can be catastrophic
changes in cis elements, several of which typically work in concert to control a particular gene's activity, are likely to have a much more limited effec
each element serves as a docking site for a particular transcription factor, some of which stimulate gene expression and others inhibit it
this modularity makes possible an infinite number of cis-element combinations that finely tune gene activity in time, space, and degree
any one sequence change is unlikely to be broadly disruptive

Coyne and Hoekstra accept only cases in which a mutation in a cis element has been demonstrated to modify a particular trait
not just to be correlated with a difference

furthermore, the duo insist that the modified trait must be shown to be beneficial in the long run
they dismiss the shavenbaby example not only because causative changes in cis-regulatory elements haven't yet been identified
but also because no one really knows whether the fine hairs on fruit fly larvae confer a selective advantage

they point instead to a large body of evidence indicating that so-called structural changes in protein-coding genes play a central role in evolution
they also point out that the small differences between the chimp and human genomes, which led Wilson and King to question whether mutations in coding regions can account for the differences between the species, still add up to plenty of meaningful gene changes
an estimated 60,000

Carroll also doesn't buy into the requirement that the new form needs to be shown to result in a selective advantage

Wray is examining whether there are any patterns in the types of mutations that are associated with different types of genes
Stern has gone a step further
he and Virginie Orgogozo of the Université Pierre et Marie Curie in Paris did a comprehensive literature survey to ferret out any evolutionarily important mutations
unlike Hoekstra and Coyne, they included data on domesticated species and didn't demand that the change be clearly adaptive
overall, cis-regulatory changes represented 22% of the 331 mutations cataloged
in comparisons between species, cis-regulatory mutations caused about 75% of the morphological evolution, they report in an article in press in Evolution

to complicate matters further, mutations in coding regions can themselves alter gene regulation
Wagner and Yale colleague Vincent Lynch make the case in an article published online on 22 May in Trends in Ecology & Evolution that mutations in transcription factors can lead to evolutionarily relevant modifications in gene expression