Genomics: Analysis of Pseudogenes and Intergenic Regions
We were the first group to assign pseudogenes comprehensively to the human genome and, for comparison, to the genomes of other organisms. Collectively, these studies enable us to determine the common "pseudofamilies" in various genomes and to address important evolutionary questions about the type of proteins that were present in the past history of an organism. In particular, they enabled us to show that there are dramatic differences in the repertoire of pseudogenes in the human genome versus those of other organisms with the human having many more processed pseudogenes (associated with highly transcribed genes such as those of the ribosome), whereas the genomes of other organisms have many more pseudogenes associated with environmental response proteins and horizontal transfer events. Our large scale assignment of pseudogenes also enabled us to precisely calibrate neutral rates of mutation in the genome. Finally, we were able to couple our pseudogene assignments with results of tiling array experiments probing the activity of intergenic regions. These studies enabled us to suggest that pseudogenes might not actually be dead at all, but that many of them are quite alive and actively transcribed. Our work with pseudogenes, and tiling arrays, and intergenic analysis has required the development of many novel technologies such as automatic assignment pipelines and statistical scoring schemes.
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