Reading between the LINEs: human genomic variation induced by LINE-1 retrotransposition.

The insertion of mobile elements into the genome represents a new class of genetic markers for the study of human evolution. Long interspersed elements (LINEs) have amplified to a copy number of about 100,000 over the last 100 million years of mammalian evolution and comprise approximately 15% of the human genome. The majority of LINE-1 (L1) elements within the human genome are 5' truncated copies of a few active L1 elements that are capable of retrotransposition. Some of the young L1 elements have inserted into the human genome so recently that populations are polymorphic for the presence of an L1 element at a particular chromosomal location. L1 insertion polymorphisms offer several advantages over other types of polymorphisms for human evolution studies. First, they are typed by rapid, simple, polymerase chain reaction (PCR)-based assays. Second, they are stable polymorphisms that rarely undergo deletion. Third, the presence of an L1 element represents identity by descent, because the probability is negligible that two different young L1 repeats would integrate independently between the exact same two nucleotides. Fourth, the ancestral state of L1 insertion polymorphisms is known to be the absence of the L1 element, which can be used to root plots/trees of population relationships. Here we report the development of a PCR-based display for the direct identification of dimorphic L1 elements from the human genome. We have also developed PCR-based assays for the characterization of six polymorphic L1 elements within the human genome. PCR analysis of human/rodent hybrid cell line DNA samples showed that the polymorphic L1 elements were located on several different chromosomes. Phylogenetic analysis of nonhuman primate DNA samples showed that all of the recently integrated "young" L1 elements were restricted to the human genome and absent from the genomes of nonhuman primates. Analysis of a diverse array of human populations showed that the allele frequencies and level of heterozygosity for each of the L1 elements was variable. Polymorphic L1 elements represent a new source of identical-by-descent variation for the study of human evolution. [The sequence data described in this paper have been submitted to the GenBank data library under accession nos. AF242435-AF242451.]

Transposition of the LINE-like retrotransposon TART to Drosophila chromosome termini.

TART, a telomere-associated DNA element from Drosophila, is shown in this paper to have structural homology to LINE (long interspersed element)-like retrotransposons and to transpose to broken chromosome ends. TART DNA was detected by in situ hybridization in 7 of 10 independent additions of DNA to a chromosome end. We found evidence that a TART element had transposed to the chromosome end in each of two additions that were examined in detail. From the DNA sequence of a TART element that recently transposed, we infer that TART encodes two proteins having significant sequence similarity to the putative proteins of many LINEs. These results support the hypothesis that TART elements preferentially retrotranspose to the termini of chromosomes as part of the essential process by which Drosophila telomeres are maintained.

Transposons in place of telomeric repeats at a Drosophila telomere.

We present the first isolation of the terminal DNA of an intact Drosophila telomere. It differs from those isolated from other eukaryotes by the lack of short tandem repeats at the terminus. The terminal 14.5 kb is composed of four tandem elements derived from two families of non-long terminal repeat retrotransposons and is subject to slow terminal loss. One of these transposon families, TART (telomere-associated retrotransposon), is described for the first time here. The other element, HeT-A, has previously been shown to transpose to broken chromosome ends. Our results provide key evidence that these elements also transpose to natural chromosome ends. We propose that the telomere-associated repetitive DNA is maintained by saltatory expansions, including terminal transpositions of specialized retrotransposons, which serve to balance terminal loss.

Frequency-dependent viability in mutant strains of Drosophila melanogaster.

We investigated the effects of genotypic frequencies on egg-to-adult viabilities in pairwise combinations of four strains of Drosophila melanogaster. The experiments involved mixture of a total of 42,000 eggs in varying proportions under controlled densities and observation of surviving adults. Viabilities were found to depend on frequencies in several genotypic combinations. In the most extreme case, the absolute viability of cn;bw females increased monotonically from 54% when common to 70% when rare. The results illustrate several statistical and methodological problems that might explain why some experiments have failed to detect frequency-dependent viabilities. These problems include heterogeneity between replications, sex differences in susceptibility to competition, and strong dependence of the experimental outcome on the choice of competitor genotypes.