Johns Hopkins University
Publishes on Chromosomal and Genetic Variations, Hemoglobinopathies and Related Disorders, RNA and protein synthesis mechanisms. 249 papers and 33.3k citations.
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Mobile elements within genomes have driven genome evolution in diverse ways. Particularly in plants and mammals, retrotransposons have accumulated to constitute a large fraction of the genome and have shaped both genes and the entire genome. Although the host can often control their numbers, massive expansions of retrotransposons have been tolerated during evolution. Now mobile elements are becoming useful tools for learning more about genome evolution and gene function.
Although LINE-1 (long interspersed nucleotide element-1, L1) retrotransposons comprise 17% of the human genome, an exhaustive search of the December 2001 "freeze" of the haploid human genome working draft sequence (95% complete) yielded only 90 L1s with intact ORFs. We demonstrate that 38 of 86 (44%) L1s are polymorphic as to their presence in human populations. We cloned 82 (91%) of the 90 L1s and found that 40 of the 82 (49%) are active in a cultured cell retrotransposition assay. From these data, we predict that there are 80-100 retrotransposition-competent L1s in an average human being. Remarkably, 84% of assayed retrotransposition capability was present in six highly active L1s (hot L1s). By comparison, four of five full-length L1s involved in recent human insertions had retrotransposition activity comparable to the six hot L1s in the human genome working draft sequence. Thus, our data indicate that most L1 retrotransposition in the human population stems from hot L1s, with the remaining elements playing a lesser role in genome plasticity.