Mark Johnston and colleagues (Clifton et al.) investigated the power of comparative genomics for analysing the
Saccharomyces cerevisiae
genome. By generating over 4 Mb of genomic sequence from seven additional Saccharomyces species, they examined how the evolutionary divergence of the species influences the ability to identify short genomic sequences with specific functions. First, they sequenced and compared small nucleolar RNA (snoRNA) genes, which are conserved in all species. In pairwise comparisons between species that are too closely related, the genes did not stand out from the high background level of sequence conservation; conversely, the genomic sequences of species that were too diverged were difficult to align. Similar results were obtained for regulatory elements, but in this case it was valuable, particularly for the more diverged species, to align orthologous genes before searching for the upstream conserved elements. The authors conclude that the optimal strategy for sequence comparison with S. cerevisiae should involve at least three other species — two closely related species, such as S. mikatae and S. bayanus, and a more divergent species, such as S. kluyveri.
By combining comparative and functional genomics, Karen Wassarman, Francis Repoila and colleagues focused on finding new genes that encode small non-coding RNAs (sRNAs) in the
Escherichia coli
genome. They first compared the genome of E. coli with closely related Salmonella and Klebsiella species, concentrating on intergenic regions, which are known to contain sRNAs. They then used oligonucleotide microarrays and Northern blot analysis to test whether the sequences were expressed. Ultimately, they identified 17 new sRNAs ranging in size from 45 to 320 bases.
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