TY - JOUR T1 - Comparative Genomics Search for Losses of Long-Established Genes on the Human Lineage A1 - Zhu, Jingchun A1 - Sanborn, J. Zachary A1 - Diekhans, Mark A1 - Lowe, Craig B A1 - Pringle, Tom H A1 - Haussler, David Y1 - 2007/12/14 N2 -
One of the most important questions in biology is to identify the genetic changes underlying evolution, especially those along the lineage leading to the modern human. Although counterintuitive, losing a gene might actually bring a selective advantage to the organism. This type of gene loss is called adaptive gene loss. Although a few cases have been characterized in the literature, this is the first study to address adaptive gene losses on a scale of the whole human genome and a time period of up to 75 million years. The difficulty of identifying adaptive gene losses is in part the large number of pseudogenes in the human genome. To circumvent this problem, we used two methods to enrich the process for the adaptive candidates. The first is a novel approach for pseudogene detection that is highly sensitive in identifying single-copy pseudogenes that bear no apparent sequence homology to any functional human genes. Second, we used the length of time a gene is functional before loss as a proxy for biological importance, which allows us to differentiate losses of long-established genes from mere losses due to functional redundancy after gene duplication.