Distinguishing protein-coding and noncoding genes in the human genome

@article{citeulike:1989097, abstract = {Although the Human Genome Project was completed 4 years ago, the catalog of human protein-coding genes remains a matter of controversy. Current catalogs list a total of {approx}24,500 putative protein-coding genes. It is broadly suspected that a large fraction of these entries are functionally meaningless ORFs present by chance in RNA transcripts, because they show no evidence of evolutionary conservation with mouse or dog. However, there is currently no scientific justification for excluding ORFs simply because they fail to show evolutionary conservation: the alternative hypothesis is that most of these ORFs are actually valid human genes that reflect gene innovation in the primate lineage or gene loss in the other lineages. Here, we reject this hypothesis by carefully analyzing the nonconserved ORFsspecifically, their properties in other primates. We show that the vast majority of these ORFs are random occurrences. The analysis yields, as a by-product, a major revision of the current human catalogs, cutting the number of protein-coding genes to {approx}20,500. Specifically, it suggests that nonconserved ORFs should be added to the human gene catalog only if there is clear evidence of an encoded protein. It also provides a principled methodology for evaluating future proposed additions to the human gene catalog. Finally, the results indicate that there has been relatively little true innovation in mammalian protein-coding genes. 10.1073/pnas.0709013104}, author = {Clamp, Michele and Fry, Ben and Kamal, Mike and Xie, Xiaohui and Cuff, James and Lin, Michael F. and Kellis, Manolis and Lindblad-Toh, Kerstin and Lander, Eric S. }, citeulike-article-id = {1989097}, doi = {10.1073/pnas.0709013104}, journal = {Proceedings of the National Academy of Sciences}, keywords = {bioinformatics, gene}, month = {November}, pages = {0709013104+}, posted-at = {2008-03-25 16:29:26}, priority = {2}, title = {Distinguishing protein-coding and noncoding genes in the human genome}, url = {http://dx.doi.org/10.1073/pnas.0709013104}, year = {2007} }

TY - JOUR ID - citeulike:1989097 L3 - citeulike-article-id:1989097 TI - Distinguishing protein-coding and noncoding genes in the human genome JF - Proceedings of the National Academy of Sciences SP - 0709013104 N2 - Although the Human Genome Project was completed 4 years ago, the catalog of human protein-coding genes remains a matter of controversy. Current catalogs list a total of {approx}24,500 putative protein-coding genes. It is broadly suspected that a large fraction of these entries are functionally meaningless ORFs present by chance in RNA transcripts, because they show no evidence of evolutionary conservation with mouse or dog. However, there is currently no scientific justification for excluding ORFs simply because they fail to show evolutionary conservation: the alternative hypothesis is that most of these ORFs are actually valid human genes that reflect gene innovation in the primate lineage or gene loss in the other lineages. Here, we reject this hypothesis by carefully analyzing the nonconserved ORFsspecifically, their properties in other primates. We show that the vast majority of these ORFs are random occurrences. The analysis yields, as a by-product, a major revision of the current human catalogs, cutting the number of protein-coding genes to {approx}20,500. Specifically, it suggests that nonconserved ORFs should be added to the human gene catalog only if there is clear evidence of an encoded protein. It also provides a principled methodology for evaluating future proposed additions to the human gene catalog. Finally, the results indicate that there has been relatively little true innovation in mammalian protein-coding genes. 10.1073/pnas.0709013104 KW - bioinformatics KW - gene AU - Clamp, Michele AU - Fry, Ben AU - Kamal, Mike AU - Xie, Xiaohui AU - Cuff, James AU - Lin, Michael AU - Kellis, Manolis AU - Lindblad-Toh, Kerstin AU - Lander, Eric PY - 2007/11/26/ UR - http://dx.doi.org/10.1073/pnas.0709013104 ER -