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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Lindblad-toh, Kerstin Clamp, Michele Fry, Ben Lin, Michael F. Kellis, Manolis Xie, Xiaohui Lander, Eric S. Kamal, Mike Cuff, James |
| Description | Author Affiliation: Clamp M ( Broad Institute of Massachusetts Institute of Technology and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA. mclamp@broad.mit.edu); |
| 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 approximately 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 ORFs-specifically, 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 approximately 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 49 |
| Volume Number | 104 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2007-12-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Genetic Code Genome, Human Genetics Genomics Open Reading Frames Proteins Animals DNA Transposable Elements Genes Mice Molecular Sequence Data Pseudogenes Sequence Analysis, DNA Research Support, N.I.H., Extramural Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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