Hot L1s account for the bulk of retrotransposition in the human population

TLDR

LINE‑1 retrotransposons comprise 17 % of the human genome, yet a 2001 genome draft identified only 90 intact L1 elements. The authors cloned 82 of the 90 L1s and tested them in a cultured‑cell retrotransposition assay, finding 40 (49 %) were active. The study shows 38 of 86 L1s are polymorphic, predicts 80–100 retrotransposition‑competent L1s per person, and finds that six hot L1s contribute 84 % of activity, implying most human L1 retrotransposition originates from these elements.

Abstract

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.