TY - JOUR
T1 - Extensive individual variation in L1 retrotransposition capability contributes to human genetic diversity
AU - Del Carmen Seleme, Maria
AU - Vetter, Melissa R.
AU - Cordaux, Richard
AU - Bastone, Laurel
AU - Batzer, Mark A.
AU - Kazazian, Haig H.
PY - 2006/4/25
Y1 - 2006/4/25
N2 - Despite being scarce in the human genome, active L1 retrotrans-posons continue to play a significant role in its evolution. Because of their recent expansion, many L1s are not fixed in humans, and, when present, their mobilization potential can vary among individuals. Previously, we showed that the great majority of retrotransposition events in humans are caused by highly active, or hot. L1s. Here, in four populations of diverse geographic origins (160 haploid genomes), we investigated the degree of sequence poly-morphism of three hot L1s and the extent of individual variation in mobilization capability of their allelic variants. For each locus, we found one previously uncharacterized allele in every three to five genomes, including some with nonsense and insertion/deletion mutations. Single or multiple nucleotide substitutions drastically affected the retrotransposition efficiency of some alleles. One-third of elements were no longer hot, and these so-called cool alleles substantially increased the range of individual susceptibility to retrotransposition events. Adding the activity of the three elements in each individual resulted in a surprising degree of variation in mobilization capability, ranging from 0% to 390% of a reference L1. These data suggest that individual variation in retrotransposition potential makes an important contribution to human genetic diversity.
AB - Despite being scarce in the human genome, active L1 retrotrans-posons continue to play a significant role in its evolution. Because of their recent expansion, many L1s are not fixed in humans, and, when present, their mobilization potential can vary among individuals. Previously, we showed that the great majority of retrotransposition events in humans are caused by highly active, or hot. L1s. Here, in four populations of diverse geographic origins (160 haploid genomes), we investigated the degree of sequence poly-morphism of three hot L1s and the extent of individual variation in mobilization capability of their allelic variants. For each locus, we found one previously uncharacterized allele in every three to five genomes, including some with nonsense and insertion/deletion mutations. Single or multiple nucleotide substitutions drastically affected the retrotransposition efficiency of some alleles. One-third of elements were no longer hot, and these so-called cool alleles substantially increased the range of individual susceptibility to retrotransposition events. Adding the activity of the three elements in each individual resulted in a surprising degree of variation in mobilization capability, ranging from 0% to 390% of a reference L1. These data suggest that individual variation in retrotransposition potential makes an important contribution to human genetic diversity.
KW - Human variation
KW - Population genetics
KW - Retrotransposon
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U2 - 10.1073/pnas.0601324103
DO - 10.1073/pnas.0601324103
M3 - Article
C2 - 16618923
AN - SCOPUS:33646256347
SN - 0027-8424
VL - 103
SP - 6611
EP - 6616
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 17
ER -