Alu elements
Alu elements are about 300 nucleotides in length and include a distinctive sequence that ends in a poly-A tail. The human gene's protein-generating capacity is considerably increased by the presence of Alu elements.
About 5 percent of alternatively spliced exons in the human genome contain an Alu sequence, probably resulting from insertion of an Alu element into an intron of a gene where it would normally be spliced out and so would not have any negative consequence for the primate.
Through mutation, however, an Alu segment can convert an intron into an exon by any alteration in the Alu sequence that generates a new 5' or 3' splice site within the intron, resulting in its recognition by the spliceosome as an exon. (Such mutations usually arise during replication.)
If the new Alu exon is only alternatively spliced-in, the organism can produce a new protein without losing the gene's original function. This results from the original, wild types of mRNA continuing to be synthesized when the Alu exon is spliced-out. Problems arise only when a mutated Alu becomes spliced constitutively such that the Alu exon is always spliced in to all the mRNAs transcripts, with the loss of the original protein.
A single nucleotide polymorphism (point mutation) is sufficient to convert some silent intronic Alu elements into real exons. At present, the human genome contains approximately 500,000 Alu elements located within introns, and 25,000 of those could become new exons by undergoing this single-point mutation. Thus, Alu sequences have the potential to continue to greatly enrich the stock of meaningful genetic information available for producing new human proteins.
Three genetic illnesses have so far been identified as being caused by misplaced Alu sequences: Alport and Sly syndromes and OAT deficiency.
(Sorek et al., Genome Research 2002; Lev-Maor et al., Science 2003; Sorek et al., Molecular Cell 2004). [s]
About 5 percent of alternatively spliced exons in the human genome contain an Alu sequence, probably resulting from insertion of an Alu element into an intron of a gene where it would normally be spliced out and so would not have any negative consequence for the primate.
Through mutation, however, an Alu segment can convert an intron into an exon by any alteration in the Alu sequence that generates a new 5' or 3' splice site within the intron, resulting in its recognition by the spliceosome as an exon. (Such mutations usually arise during replication.)
If the new Alu exon is only alternatively spliced-in, the organism can produce a new protein without losing the gene's original function. This results from the original, wild types of mRNA continuing to be synthesized when the Alu exon is spliced-out. Problems arise only when a mutated Alu becomes spliced constitutively such that the Alu exon is always spliced in to all the mRNAs transcripts, with the loss of the original protein.
A single nucleotide polymorphism (point mutation) is sufficient to convert some silent intronic Alu elements into real exons. At present, the human genome contains approximately 500,000 Alu elements located within introns, and 25,000 of those could become new exons by undergoing this single-point mutation. Thus, Alu sequences have the potential to continue to greatly enrich the stock of meaningful genetic information available for producing new human proteins.
Three genetic illnesses have so far been identified as being caused by misplaced Alu sequences: Alport and Sly syndromes and OAT deficiency.
(Sorek et al., Genome Research 2002; Lev-Maor et al., Science 2003; Sorek et al., Molecular Cell 2004). [s]
posted | 12/24/2007 12:02:00 PM
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