One of the big surprises of the genome project was the final tally of how many genes it takes to make a human. The projects' prediction of thirty to forty thousand falls far short of earlier estimates, some of which ran as high as one hundred fifty thousand genes. This apparent shortfall has left scientists scrambling to explain how, with only modestly more genes, humans are so much more complex than the fruit fly.

Ignoring the unthinkable-that we're really not that special-one popular face-saving suggestion is that our biological complexity may be due to thousands of small RNAs that do not code for protein but have important functions of their own. In theory this hypothesis is attractive, but proving it presents a challenge. In tomorrow's Science, however, researchers report that RNA transcription from human chromosomes 21 and 22 is much more widespread than previously thought.

Tom Gingeras and colleagues from Affymetrix Inc., Santa Clara, California, used oligonucleotide arrays to determine what part of these chromosomes are actively transcribed. The arrays contained over one million oligos, each 25 base pairs long, chosen to complement the entire length of the chromosomes (35 million base pairs) with, on average, a gap of 10 bp between each binding site. The arrays were then hybridized with cDNAs made from 11 different cell lines.

The authors found that almost 90 percent of the oligos hybridized to regions heretofore not recognized as coding for protein. In addition, more than half of these were more than 300 bp from the nearest exon. 63 transcripts predicted by the analysis were chosen for further analysis and 44 of these could be amplified by RT-PCR, confirming their presence in the mRNA pool. 16 amplified products were used in Northern analysis, revealing 7 transcripts ranging in size from 0.6 to 10 kb.

Overall, the data indicate that there may be up to ten-fold more sites of transcription than predicted by the genome project, though the authors caution that their array could mistake homologs transcribed from chromosomes other than 21 and 22 as being novel transcripts. The big question is what are these new transcripts? Some of them are extended exons of known genes-for example, the authors found larger versions of the DiGeroge syndrome gene-but it is tempting to speculate that many of them may be non-coding RNAs. Whatever the outcome, many will be relieved to find out we really are complex after all.—Tom Fagan

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Primary Papers

  1. . Large-scale transcriptional activity in chromosomes 21 and 22. Science. 2002 May 3;296(5569):916-9. PubMed.