A specific gene conversion of an Alu family member in the LDL-receptor gene
- Lawrence Livermore National Lab., CA (United States)
There are about 500,000 Alu family members dispersed throughout the human genome. Each of these elements is about 300 bp long and they are spread through an RNA-mediated transposition process termed retroposition. The Alu elements are not identical in sequence, but instead seem to be randomly diverged from several subfamily consensus sequences. These subfamilies can be roughly divided, based on diagnostic nucleotide positions, into groups of Alu sequences inserted during different stages in primate evolution. A PCR-based assay in which we amplify a specific Alu-containing site in the genomes of different primates allows us to detect the time of insertion of that individual Alu element in the primate genome. In studying members of one of the youngest Alu subfamilies, Sb2, we detected one element that had apparently inserted over 25 million years ago, much earlier than any other Sb2 element tested. Upon sequencing the amplified PCR products, we found that an Alu was in that precise location for 25 million years, but only in the human genome was it an Sb2 element. Its sequence was consistent with the oldest (PS) Alu subfamily in the other primates. This element evolves as expected throughout primates with the exception of the human, where it has suddenly acquired 16 separate diagnostic subfamily mutations. Although the exact mechanism is unknown, this Alu element has been specifically gene converted by an Alu element from this newer subfamily, without affecting the flanking sequences at all. It is clear that the majority of Alu subfamily evolution is dominated by insertion processes. However, this event shows that some of the details of Alu subfamily evolution may also be affected by gene conservation. Studies on several humans also show that this locus continued to accumulate mutations at an exceptionally high level after the conversion, making it useful as a polymorphic marker for the LDL-receptor locus.
- OSTI ID:
- 133891
- Report Number(s):
- CONF-941009--
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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