Sing the Genome Electric Excited Cells Adjust Their Splicing 英文参考文献.docVIP

Primer Sing the Genome Electric: Excited Cells Adjust Their Splicing Manuel Ares, Jr. T hose of us who study alternative splicing like to think it is the driving force behind the rapid evolution of human nature. Of course, we could be wrong, but what other explanation can account for the amazing increase in complexity and capability of the human species without a corresponding increase in gene number? Humans have an estimated 20,000–25,000 protein-coding genes, compared to about 19,200 for worms. Are we simply very smart worms? Our complexity is most evident (to us) in that most special of special human features, the brain. How did only 5 million years of evolution squeeze so much out of the primate genome so quickly? Perhaps it is not so much the written poem, but the reading that matters. While it is true that RNA polymerase controls what part of the genome to read and when, it is the spliceosome and its splicing factors—the machinery that removes noncoding information from nascent gene transcripts to make messenger RNA (mRNA)—that provide the interpretive pace, phraseology, emphasis, and intonation to the reading. The splicing machinery, through the process of alternative splicing, can produce different mRNAs and hence different proteins from the same gene, depending on the biological circumstances. Human genes produce on average three distinctly spliced alternative mRNAs rather than only one, and some genes have the potential to produce thousands of distinct mRNAs through alternative splicing. The view that alternative splicing adds the genetic complexity that makes us human may help us feel better about sharing most of our genes with less psychologically complex organisms. But is it true? Perhaps there is more to it than our own self-absorption. In this issue of PLoS Biology, An and Grabowski [1] and Lee et al. [2] connect the electrical activity of neurons with complex and coordinated regulation of gene expression at the level of alternative splicing. doi:10.1