Insertion of an Alu SINE in the human homologue of theMlvi-2 locus

Abstract

Fifty-nine human DNA samples derived from either normal tissues or hematopoietic neoplasias were examined for rearrangements in the Mlvi-2 locus, a putative oncogene. The rearranged Mlvi-2 sequences in one of them, a B cell lymphoma, were shown to result from the insertion of an approximately 300 bp DNA fragment that hybridized to a human Alu probe. DNA sequence analysis of both the rearranged and the nonrearranged allele around the site of the insertion revealed the following: a) the insert was 88.4% homologous to the consensus sequence of the Alu family of repeats and 75% homologous to the Alu related sequence in the human 7SL RNA; b) similar to other sequenced SINES, a poly(d.A) tract was present at the 3' end of this element; c) an 8 bp direct repeat was present at both ends of the inserted element; d) this repeat was present as a single copy in the unrearranged allele. We conclude from these findings that: Alu sequences can transpose and that the direct repeats flanking certain Alu SINES may be generated by the duplication of single copy cellular sequences at the site of the insertion. Furthermore the recent nature of the Alu insertion in the Mlvi-2 locus coupled to the low degree of homology of the inserted Alu to the Alu related sequence in the 7SL RNA suggest that this event did not occur via reverse transcription and reintegration of the 7SL RNA.

Multiple dispersed loci produce small cytoplasmic Alu RNA.

“…Although the Alu insertions that contributed variability to the human genome were inherited through the germ line, it is plausible that transposition is not limited to this tissue and that Alu insertion may also occur in somatic cells (9,24). Identification of RNAs that correspond to primary transcripts of Alu sequences (7,30) (Fig.…”

The Decline in Human Alu Retroposition Was Accompanied by an Asymmetric Decrease in SRP9/14 Binding to Dimeric Alu RNA and Increased Expression of Small Cytoplasmic Alu RNA

“…The great majority of Alu repeats in human DNA were fixed in an ancestral primate genome before the emergence of the human lineage (reviewed in reference 40). Although Alu retroposition indeed occurs in humans (16,35,46,48), the available data indicate that (i) certain Alu sequences have been more prolific than others and (ii) the rate of new Alu insertions into the genome has declined during recent periods of primate evolution (6,40,41).The Alu retroposons that were actively proliferating during ancient, intermediate, and modern evolutionary times are reflected by three subfamilies of Alu sequences that remain distinguishable in human DNA (7,23,38,44,50; reviewed in references 40 and 41). The subfamily consensus sequence referred to as Alu Sx (formerly PS and Major; see nomenclature in reference 2) represents the sequence that produced approximately 85% of the Alus in the human genome 60 to 30 million years ago.…”

“…The great majority of Alu repeats in human DNA were fixed in an ancestral primate genome before the emergence of the human lineage (reviewed in reference 40). Although Alu retroposition indeed occurs in humans (16,35,46,48), the available data indicate that (i) certain Alu sequences have been more prolific than others and (ii) the rate of new Alu insertions into the genome has declined during recent periods of primate evolution (6,40,41).…”

A Trinucleotide Repeat-Associated Increase in the Level of Alu RNA-Binding Protein Occurred during the Same Period as the Major Alu Amplification That Accompanied Anthropoid Evolution

“…While relatively few Alu sequences continue to transpose in humans, a substantial fraction of these have caused genetic variability and/or gene disruptions that have come to the at-tention of geneticists (1,14,22,25,39,42,54,73). Further characterization of human-specific Alu sequences has allowed the calculation of an Alu de novo transposition rate of 1 in 100 human births (13).…”