Biomedical subjects

Jungnam Lee

Publications and source records attributed to Jungnam Lee.

5 recordsLinked to original sources

PubMed2006

Different evolutionary fates of recently integrated human and chimpanzee LINE-1 retrotransposons.

The long interspersed element-1 (LINE-1 or L1) is a highly successful retrotransposon in mammals. L1 elements have continued to actively propagate subsequent to the human-chimpanzee divergence, approximately 6 million years ago, resulting in species-specific inserts. Here, we report a detailed characterization of chimpanzee-specific L1 subfamily diversity and a comparison with their human-specific counterparts. Our results indicate that L1 elements have experienced different evolutionary fates in humans and chimpanzees within the past approximately 6 million years. Although the species-specific L1 copy numbers are on the same order in both species (1200-2000 copies), the number of retrotransposition-competent elements appears to be much higher in the human genome than in the chimpanzee genome. Also, while human L1 subfamilies belong to the same lineage, we identified two lineages of recently integrated L1 subfamilies in the chimpanzee genome. The two lineages seem to have coexisted for several million years, but only one shows evidence of expansion within the past three million years. These differential evolutionary paths may be the result of random variation, or the product of competition between L1 subfamily lineages. Our results suggest that the coexistence of several L1 subfamily lineages within a species may be resolved in a very short evolutionary period of time, perhaps in just a few million years. Therefore, the chimpanzee genome constitutes an excellent model in which to analyze the evolutionary dynamics of L1 retrotransposons.

5' Untranslated Regions↗

PubMed2006

Human genomic deletions mediated by recombination between Alu elements.

Recombination between Alu elements results in genomic deletions associated with many human genetic disorders. Here, we compare the reference human and chimpanzee genomes to determine the magnitude of this recombination process in the human lineage since the human-chimpanzee divergence approximately 6 million years ago. Combining computational data mining and wet-bench experimental verification, we identified 492 human-specific deletions (for a total of approximately 400 kb) attributable to this process, a significant component of the insertion/deletion spectrum of the human genome. The majority of the deletions (295 of 492) coincide with known or predicted genes (including 3 that deleted functional exons, as compared with orthologous chimpanzee genes), which implicates this process in creating a substantial portion of the genomic differences between humans and chimpanzees. Overall, we found that Alu recombination-mediated genomic deletion has had a much higher impact than was inferred from previously identified isolated events and that it continues to contribute to the dynamic nature of the human genome.

Animals↗

PubMed2006

Recently integrated Alu retrotransposons are essentially neutral residents of the human genome.

Alu elements represent the largest family of human mobile elements in copy number. A controversial issue with implications for both Alu biology and human genome evolution is whether selective pressures are affecting Alu elements on a large scale. To address this issue, we analyzed the genomic distribution of the three youngest known human Alu subfamilies (Ya5a2, Ya8 and Yb9) in conjunction with their insertion polymorphism status in the human population, since selection can only act on polymorphic elements. Our results indicate that: (i) polymorphic and fixed recently integrated Alu elements are found in genomic regions whose GC contents are statistically indistinguishable, and (ii) recently integrated Alu elements are inserted randomly, regardless of the GC content of the surrounding genomic DNA. These results provide strong evidence that recently integrated "young" Alu elements are not subject to positive or negative selection on a large scale. Therefore, young Alu elements can be regarded as essentially neutral residents of the human genome. These results also imply that selective processes specifically targeting Alu elements can be ruled out as explanations for the accumulation of Alu elements in GC-rich regions of the human genome.

Alu Elements↗

PubMed2005

Imipenem-resistant Achromobacter xylosoxidans carrying blaVIM-2-containing class 1 integron.

We characterized seven isolates of imipenem-resistant Achromobacter xylosoxidans that were isolated from patients hospitalized in the intensive care unit at a tertiary hospital in Korea during 2001 to 2003. From the analysis with an isoelectric focusing, polymerase chain reaction, and sequencing methods, all isolates were found to produce VIM-2, OXA-30, and chromosomal AmpC beta-lactamase with a pI of 8.4. They showed a similar antibiogram, which were resistant to all tested aminoglycosides as well as beta-lactams including imipenem (16-32 mg/L) and aztreonam (128 mg/L), and a same DNA fingerprinting pattern by random amplified polymorphic DNA analysis, suggesting that these originated from a single clone. From the analysis of integron structure carried by an isolate of A. xylosoxidans CBU1760, bla(VIM-2) was found to be part of a gene cassette carried on a class 1 integron (3.4 kb) containing three aacA4 gene cassettes. This is the first report of bla(VIM-2) in A. xylosoxidans.

Achromobacter denitrificans↗

PubMed2005

Genomic rearrangements by LINE-1 insertion-mediated deletion in the human and chimpanzee lineages.

Long INterspersed Elements (LINE-1s or L1s) are abundant non-LTR retrotransposons in mammalian genomes that are capable of insertional mutagenesis. They have been associated with target site deletions upon insertion in cell culture studies of retrotransposition. Here, we report 50 deletion events in the human and chimpanzee genomes directly linked to the insertion of L1 elements, resulting in the loss of approximately 18 kb of sequence from the human genome and approximately 15 kb from the chimpanzee genome. Our data suggest that during the primate radiation, L1 insertions may have deleted up to 7.5 Mb of target genomic sequences. While the results of our in vivo analysis differ from those of previous cell culture assays of L1 insertion-mediated deletions in terms of the size and rate of sequence deletion, evolutionary factors can reconcile the differences. We report a pattern of genomic deletion sizes similar to those created during the retrotransposition of Alu elements. Our study provides support for the existence of different mechanisms for small and large L1-mediated deletions, and we present a model for the correlation of L1 element size and the corresponding deletion size. In addition, we show that internal rearrangements can modify L1 structure during retrotransposition events associated with large deletions.

Animals↗