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Book Summary:
Mobile elements comprise approximately 50% of the human genome and have significant influence on human genomic architecture and stability. SINEs (Short INterspersed Elements) are a class of non-autonomous mobile elements that are usually <500 bp in length and have no open reading frames. As the most successful SINEs in primate, Alu elements have expanded to more than one million copies in the human genome. To understand the biology of Alu family of mobile elements, we first analyzed the AluYd lineage in the human genome. Computational analysis of the AluYd lineage from the human genome draft sequence resulted in the identification of two new AluYd subfamilies, Yd3 and Yd6. Two hundred AluYd3 and Yd6 loci were screened to determine their phylogenetic origin and associated levels of human genomic diversity. Second, we examined the mutation spectra of Alu elements in the human genome. We analyzed the mutation patterns for 5296 Alu elements comprising 20 subfamilies. Our results indicate a relatively constant CpG versus non-CpG substitution ratio of ∼6 for the young ( AluY) and intermediate (AluS) Alu subfamilies and a more complex non-linear relationship when older ( AluJ) subfamilies were included in the analysis. This study provides an updated, more accurate estimate of the disparity in the rate of mutation within Alu elements and provides a better understanding of the CpG decay process during primate evolution. Third, we analyzed the evolutionary history of AluYb lineage. We show that the major AluYb lineage expansion is human specific while the lineage originated in early hominoid evolution. We suggest that the evolutionary success of the Alu family may be driven at least in part by “stealth driver” elements that maintain low retrotranspositional activity over extended periods of time and occasionally produce short-lived hyperactive copies responsible for the formation and remarkable expansion of Alu elements within the genome. Finally, we identified 285 Alu insertion loci that have Alu elements integrated in sixteen different Old World monkey genomes at various time and utilized these elements to construct a phylogenetic tree of old world monkeys. Our study represents one of the most robust Cercopithecid molecular phylogenies reported to date. |
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