Regulatory divergence modifies limb length between mammals

@article{citeulike:2238970, abstract = {Natural selection acts on variation within populations, resulting in modified organ morphology, physiology, and ultimately the formation of new species. Although variation in orthologous proteins can contribute to these modifications, differences in DNA sequences regulating gene expression may be a primary source of variation. We replaced a limb-specific transcriptional enhancer of the mouse Prx1 locus with the orthologous sequence from a bat. Prx1 expression directed by the bat enhancer results in elevated transcript levels in developing forelimb bones and forelimbs that are significantly longer than controls because of endochondral bone formation alterations. Surprisingly, deletion of the mouse Prx1 limb enhancer results in normal forelimb length and Prx1 expression, revealing regulatory redundancy. These findings suggest that mutations accumulating in pre-existing noncoding regulatory sequences within a population are a source of variation for the evolution of morphological differences between species and that cis-regulatory redundancy may facilitate accumulation of such mutations. 10.1101/gad.1620408}, author = {Cretekos, Chris J. and Wang, Ying and Green, Eric D. and Nisc and Martin, James F. and Rasweiler, John J. and Behringer, Richard R. }, citeulike-article-id = {2238970}, doi = {10.1101/gad.1620408}, journal = {Genes Dev.}, keywords = {cis-regulatory, mammals}, month = {January}, number = {2}, pages = {141--151}, posted-at = {2008-05-29 10:25:38}, priority = {2}, title = {Regulatory divergence modifies limb length between mammals}, url = {http://dx.doi.org/10.1101/gad.1620408}, volume = {22}, year = {2008} }

TY - JOUR ID - citeulike:2238970 L3 - citeulike-article-id:2238970 TI - Regulatory divergence modifies limb length between mammals JF - Genes Dev. VL - 22 IS - 2 SP - 141 EP - 151 N2 - Natural selection acts on variation within populations, resulting in modified organ morphology, physiology, and ultimately the formation of new species. Although variation in orthologous proteins can contribute to these modifications, differences in DNA sequences regulating gene expression may be a primary source of variation. We replaced a limb-specific transcriptional enhancer of the mouse Prx1 locus with the orthologous sequence from a bat. Prx1 expression directed by the bat enhancer results in elevated transcript levels in developing forelimb bones and forelimbs that are significantly longer than controls because of endochondral bone formation alterations. Surprisingly, deletion of the mouse Prx1 limb enhancer results in normal forelimb length and Prx1 expression, revealing regulatory redundancy. These findings suggest that mutations accumulating in pre-existing noncoding regulatory sequences within a population are a source of variation for the evolution of morphological differences between species and that cis-regulatory redundancy may facilitate accumulation of such mutations. 10.1101/gad.1620408 KW - cis-regulatory KW - mammals AU - Cretekos, Chris AU - Wang, Ying AU - Green, Eric AU - Nisc AU - Martin, James AU - Rasweiler, John AU - Behringer, Richard PY - 2008/01/15/ UR - http://dx.doi.org/10.1101/gad.1620408 ER -