Comparative genomics at the vertebrate extremes.

@article{citeulike:1206695, address = {DOE Joint Genome Institute, Walnut Creek, California 94598, USA.}, author = {Boffelli, D. and Nobrega, M. A. and Rubin, E. M. }, citeulike-article-id = {1206695}, comment = {This paper tackles a very clear question: can comparative genomics help annotate the human genome (and other genomes) better? With one genome, we will rely on experimental results, gene models or any other models for functional elements (like miRNA) to identify them. However our knowledge is still insufficient for something as well studied as protein coding genes, and even close to 0 for cis-elements, which are made of individual transcription factor binding sites (TFBS). Comparative genomics approach essentially uses evolution process as a sift. Mutations accumulate and get fixed in non-functional regions while most mutations that affect functional regions are purged by natural selection. However this approach has two pitfalls: 1. functional regions evolve between species and thus unconstrained regions may be due to adaptive evolution; 2. regional variation of mutation rate make it difficult to identify real functional elements from sequences conserved by chance; 3. some functional elements, like enhancers, may evolve at sequence level while maintaining its function under stabilizing selection. This is possible because enhancers are made up of redundant, short and degenerate TFBS. Presumably compensatory evolution would be frequent in these regions making sequence similarity melt down pretty fast. several points: * in human and fish, some enhancers can be MB away from the gene being regulated * order of TFBS may be important also. }, doi = {10.1038/nrg1350}, issn = {1471-0056}, journal = {Nat Rev Genet}, keywords = {cis\_regulatory\_elements, cis\_regulatory\_evolution, review}, month = {June}, number = {6}, pages = {456--465}, posted-at = {2008-04-14 05:25:41}, priority = {5}, title = {Comparative genomics at the vertebrate extremes.}, url = {http://dx.doi.org/10.1038/nrg1350}, volume = {5}, year = {2004} }

TY - JOUR ID - citeulike:1206695 L3 - citeulike-article-id:1206695 TI - Comparative genomics at the vertebrate extremes. JF - Nat Rev Genet VL - 5 IS - 6 SP - 456 EP - 465 AD - DOE Joint Genome Institute, Walnut Creek, California 94598, USA. SN - 1471-0056 KW - cis_regulatory_elements KW - cis_regulatory_evolution KW - review N1 - This paper tackles a very clear question: can comparative genomics help annotate the human genome (and other genomes) better? With one genome, we will rely on experimental results, gene models or any other models for functional elements (like miRNA) to identify them. However our knowledge is still insufficient for something as well studied as protein coding genes, and even close to 0 for cis-elements, which are made of individual transcription factor binding sites (TFBS). Comparative genomics approach essentially uses evolution process as a sift. Mutations accumulate and get fixed in non-functional regions while most mutations that affect functional regions are purged by natural selection. However this approach has two pitfalls: 1. functional regions evolve between species and thus unconstrained regions may be due to adaptive evolution; 2. regional variation of mutation rate make it difficult to identify real functional elements from sequences conserved by chance; 3. some functional elements, like enhancers, may evolve at sequence level while maintaining its function under stabilizing selection. This is possible because enhancers are made up of redundant, short and degenerate TFBS. Presumably compensatory evolution would be frequent in these regions making sequence similarity melt down pretty fast. several points: * in human and fish, some enhancers can be MB away from the gene being regulated * order of TFBS may be important also. AU - Boffelli, D AU - Nobrega, MA AU - Rubin, EM PY - 2004/06// UR - http://dx.doi.org/10.1038/nrg1350 ER -