More, more, more! That is the cry from comparative geneticists, who can't wait to get their hands on newly minted genome sequences. Thanks to the growing availability of such data, their research has gathered unprecedented momentum over the past twelve months. They have gained fresh insights into the regulatory sequences that control the activity of each organism's genes, and into the evolutionary forces that have shaped modern genomes.
“Before, it was like a cottage industry — comparing bits of sequence here and there — but now we're routinely comparing whole genomes with implications that are much farther reaching,” says Evan Eichler, a comparative geneticist at Case Western Reserve University in Cleveland, Ohio.
Tracing the 'footprints' of regulatory sequences involves comparing the genomes of several related species. Make multiple comparisons, and conserved regulatory elements should stand out from the 'noise' of sequences shared between close relatives simply through common descent. The more genomes the better, according to researchers who this year completed such comparisons for several related yeast species1,2.
Analyses of this type are particularly informative if they include both near and far evolutionary relatives — as was illustrated by reports that identified potential regulatory elements in the human genome by comparing chunks of our sequence with those of vertebrates as diverse as other primates, the platypus, chickens and fish3,4,5.
Comparisons between species have also revised estimates of the total number of genes possessed by important lab organisms. The tally for the baker's yeast Saccharomyces cerevisiae, for instance, has been reduced by 500 genes, following the analysis of three related yeast species1. Meanwhile, the nematode Caenorhabditis elegans has gained 1,300 or so genes from comparisons with its cousin C. briggsae6. Our own gene tally, as recorded on the Ensembl genome-browser website, has slipped this year from about 31,000 to just under 25,000, following comparisons with various other vertebrate sequences.
Comparative analysis has also taught us a thing or two about genome evolution. Over the eons, genomes have been flipped and flopped, added to and chopped, to give rise to new genes and entire gene families. Through cross-species comparisons, it is possible to determine when these changes arose. Comparing various bits of human sequences with those of other primates4,7, for instance, has revealed events that have sculpted our genome throughout evolution. The Y chromosome8, for example, seems to have a neat trick for copying important male-specific genes to protect them from being lost as the chromosome degrades down the generations.
Researchers now want to devise experiments to explore the predictions made by comparative genomics. For instance, Mark Johnston of the Washington University School of Medicine in St Louis, Missouri, is putting the proposed regulatory elements identified in yeast2 to the test in various ways. One assay involves throwing them onto 'chips' carrying proteins known to bind to regulatory regions of DNA, to see if any of them take the bait.
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Dennis, C. Compare and contrast. Nature 426, 750–751 (2003). https://doi.org/10.1038/426750b
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DOI: https://doi.org/10.1038/426750b
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