Potential Gene Conversion and Source Genes for Recently Integrated Alu Elements

Abstract

Alu elements comprise >10% of the human genome. We have used a computational biology approach to analyze the human genomic DNA sequence databases to determine the impact of gene conversion on the sequence diversity of recently integrated Alu elements and to identify Alu elements that were potentially retroposition competent. We analyzed 269 Alu Ya5 elements and identified 23 members of a new Alu subfamily termed Ya5a2 with an estimated copy number of 35 members, including the de novo Alu insertion in the NF1 gene. Our analysis of Alu elements containing one to four (Ya1-Ya4) of the Ya5 subfamily-specific mutations suggests that gene conversion contributed as much as 10%-20% of the variation between recently integrated Alu elements. In addition, analysis of the middle A-rich region of the different Alu Ya5 members indicates a tendency toward expansion of this region and subsequent generation of simple sequence repeats. Mining the databases for putative retroposition-competent elements that share 100% nucleotide identity to the previously reported de novo Alu insertions linked to human diseases resulted in the retrieval of 13 exact matches to the NF1 Alu repeat, three to the Alu element in BRCA2, and one to the Alu element in FGFR2 (Apert syndrome). Transient transfections of the potential source gene for the Apert's Alu with its endogenous flanking genomic sequences demonstrated the transcriptional and presumptive transpositional competency of the element.

Repeat-Induced Point Mutation and the Population Structure of Transposable Elements in Microbotryum violaceum

“…A final possible explanation for the proliferation of ments of Drosophila melanogaster (Maside et al 2003), Ty1 elements of Saccharomyces cerevisiae, and human Alu elements (Roy et al 2000). Our sequence data from M. violaceum are consistent with gene conversion between the elements on the same chromosome.…”

Whole genome computational comparative genomics: A fruitful approach for ascertaining Alu insertion polymorphisms

“…Until very recently (Bennett et al, 2004), the majority of previously known polymorphic Alu insertion loci were members of the closely related Y subfamilies, with the majority from the Ya5 and Yb8 subfamilies (Batzer et al, 1990;Roy et al, 2000). A comprehensive assessment of the Alu insertion activity for all subfamilies has not been previously possible due to the limited number of polymorphic insertions available and the fact that most of these polymorphic insertions were obtained through a biased subfamily-specific selective screening.…”

Human Endogenous Retroviral Elements as Indicators of Ectopic Recombination Events in the Primate Genome

“…As is true for repetitive elements in general, in addition to expansion in the genome through transposition mechanisms, these elements can also undergo unequal crossing over and gene conversion (Kass et al 1995;Roy et al 2000;Roy-Engel et al 2002). The capacity to mediate such ectopic recombination events has led to speculation that repetitive elements may be major contributors to the genome plasticity of their host species (Lower et al 1996).…”