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When molecular biologists began analyzing the complete sequence of the human genome in mid-2001, one surprising observation was that humans have relatively few genes. We may have as few as 30,000 genes, only about two
Introns are removed by the spliceosomes.
splice sites n A
The sensitivity of the human ear to a wide range of sound frequencies is due to alternative splicing of a potassium channel gene, giving rise to a set of related proteins whose exact form varies with the position in the cochlea.
mRNA messanger RNA
spliceosomes RNA-protein complexes that remove introns from RNA transcripts.
times as many as the much simpler fruit fly, Drosophila melanogaster. How can the much greater size and complexity of humans be encoded in only twice the number of genes required by a fly? The answer to this paradox is not fully understood, but it appears that humans and other mammals may be more adept than other organisms at encoding many different proteins from each gene. One way they do this is through alternative splicing, the processing of a single RNA transcript to generate more than one type of protein.
In most eukaryotic genes, the protein-coding sequences, termed exons, are interrupted by stretches of sequence, termed introns, that have no protein-coding information. After the gene is copied, or transcribed, to RNA, the introns are removed from this "pre-mRNA," and the exons are spliced together to form a mature mRNA, consisting of one contiguous protein-coding sequence. In addition, the complete mRNA contains upstream and downstream sequences flanking the coding sequences. These sequences do not encode protein, but help to regulate translation of the mRNA into protein. Variations in the splice pattern lead to alternative transcripts and alternative proteins.
Splicing is accomplished in the cell's nucleus by spliceosomes, which are molecular machines composed of proteins and small RNA molecules. The boundaries between exons and introns in a pre-mRNA are marked very subtly. Certain segments of the pre-mRNA, termed splice sites, direct the spliceosomes to the precise positions in the transcript where they can excise introns and splice together exons. Splice sites are short sequences, typically less than ten bases long. 5' splice sites mark the 5' end of introns; 3' splice sites define the 3' end of introns. ("Five prime" and "three prime" refer to the upstream and downstream ends of the RNA.)
Although splice sites often can be recognized as such by common patterns in their base sequence, there are many variations on the basic splice
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