|Liu, Ge - George|
Submitted to: Genome Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/30/2008
Publication Date: 5/1/2009
Publication URL: http://hdl.handle.net/10113/36273
Citation: Liu, G., Alkan, C., Zhao, S., Eichler, E.E. 2009. Comparative Analysis of Alu Repeats in Primate Genomes. Genome Research. 19(5):876-885. Interpretive Summary: We previously did a large-scale comparative genome analysis on high-quality finished genomic sequence from cattle, dog, and human. We estimated the pattern, frequency, and nature of repetitive sequences and their contribution to the whole genome size. Differential turn-over patterns of lineage-specific or ancestral repetitive sequences were found to account for the overall size differences among cattle, dog and human genomes. In this study, we used one of the short intersperse repetitive elements -- Alu as an example to estimate their contributions to the primate genome architecture. With large-scale randomly sampled genome sequences now available, we performed an unbiased characterization of Alu repeats using these representative sequence data. We found that different distribution patterns exist in closely related primate species. We identified lineage specific Alu elements in nonhuman species which contain diagnostic mutations distinct from human counterparts. Our results supported that a burst of Alu activities occurred during the emergence of simians (35 million years ago) after the divergence of prosimians (55 million years ago), which confirmed the master genes hypothesis for Alu amplifications with individual lineage. These new lineage specific Alu subfamilies expand our understanding of Alu evolution and their contributions to primate genome architecture. This work provided us an established software platform to further analyze the transposable elements and their contribution in the emerging bovine genome assembly.
Technical Abstract: Background: Alu repeats are SINEs (Short intersperse repetitive elements) which enjoy a successful application in genome evolution, population biology, phylogenetics and forensics. Human Alu consensus sequences were widely used as surrogates in nonhuman primate studies with an assumption that all primates share the same Alu elements. With large-scale randomly sampled genome sequences becoming available, it is worthwhile to perform an unbiased characterization of Alu repeats in nonhuman primates using these representative sequence data. Results: Using BAC (Bacteria Artificial Chromosome) end sequences and genomic sequences, we did a global assess of the divergence distributions, phylogenies and consensus sequences for both ancestral and lineage specific Alu elements in primates including lemur, marmoset, macaque, baboon, chimpanzee as compared to human. We found that in prosimians like lemur, Alu elements had a more broad and symmetric distribution and displayed a slower decline in recent Alu activity. While in simians, Alu elements had skewed distributions shifting to the ancient elements and accelerated declining rates in recent Alu activities. Lineage specific Alu elements in lemur, marmoset, macaque and baboon contain diagnostic mutations distinct from human counterparts – Alu J, S and Y subfamilies, respectively. These lineage specific Alu elements were estimated to emerge 15-27 mya (million years ago) and might be still active in their hosts. Conclusions: Our results supported that a burst of Alu activities occurred during the emergence of simians (35 mya) after the divergence of prosimians (55 mya), which confirmed the master genes hypothesis for Alu amplifications with individual primate lineage. These new lineage specific Alu subfamilies expand our understanding of Alu evolution and their contributions to primate and mammalian genome architecture.