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Unexpressed But Indispensable -- The DNA Sequences That Control Development

Amidst the hoopla over the exact number of genes we have in our genome—more than a fruitfly, fewer than a rice plant—a more fundamental genetic truth has often been obscured. The expression of 20,000?0,000 genes is under the control of an uncounted host of non-coding sequences, which bind transcription factors and thereby regulate when and where genes are expressed. Unlike coding sequences, whose signatures are easy to spot, the characteristic features of non-coding regulatory elements are largely unknown, making their discovery by simple sequence analysis difficult. In this issue, Greg Elgar and colleagues attack this problem by comparing the non-coding sequences of the human and the pufferfish.

Since the last common ancestor of these two species existed 450 million years ago, the authors reasoned that non-coding sequences conserved between them are likely to be fundamental to vertebrate development. Through sequence alignment with increasingly strict criteria, they identified 1,373 highly conserved non-coding elements (CNEs), with an average length of about 200 base pairs. The average sequence match is 84%: not perfect, but much higher than for coding regions shared by humans and pufferfish. A quick check showed that virtually all the sequences also occurred in rodents, chickens, and zebrafish, but not in the nematode, fruitfly, or even the sea squirt, a primitive non-vertebrate chordate.

CNEs are not spread uniformly throughout the genome. Instead, they are bunched together in fewer than 200 clusters, most of them in close proximity to genes implicated in transcriptional regulation or development. This clustering of CNEs suggests they may not only attract transcription factors, but may also influence the local topology of the DNA, thereby controlling access to their associated gene. Several clusters also appear in regions without any known genes—the identification of these clusters might lead to the discovery of new developmentally significant gene
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Source:PLoS


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