Phylogenetic roots of Alu-mediated rearrangements leading to cancer.
There are over a million Alu repetitive elements dispersed throughout the human genome, and a high level of Alu-sequence similarity ensures a strong propensity for unequal crossover events, some of which have lead to deleterious oncogenic rearrangements. Furthermore, Alu insertions introduce consensus 3' splice sites, which potentially facilitate alternative splicing. Not surprisingly, Alu-mediated defective splicing has also been associated with cancer. To investigate a possible correlation between the expansion of Alu repeats associated with primate divergence and predisposition to cancer, 4 Alu-mediated rearrangements--known to be the basis of cancer--were selected for phylogenetic analysis of the necessary genotype. In these 4 cases, it was determined that the different phylogenetic age of the oncogenic recombination-prone genotype reflected the evolutionary history of Alu repeats spreading to new genomic sites. Our data implies that the evolutionary expansion of Alu repeats to new genomic locations establishes new predispositions to cancer in various primate species.
Gibbons
Rosaleen
R
Department of Biochemistry, University of California, Riverside, CA 92521, USA.
Dugaiczyk
Achilles
A
D020087:Alu Elements / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002869:Chromosome Aberrations; D019143:Evolution, Molecular; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics*; D010802:Phylogeny; D011323:Primates / Q000235:genetics*; D022821:RNA Splice Sites
D022821:RNA Splice Sites