Why genome analysis?

Abstract

The field of comparative genomics is coming of age at an almost frightening speed. The first complete genome sequence of a cellular life form – the parasitic bacterium Haemophilus influenzae – was reported in 1995. Now, only 3.5 years later, we have about 20 complete genomes of bacteria, archaea and eukaryotes, and many more are in the pipeline. These genomes are changing the landscape of today's biology. Indeed, these days, almost all research in molecular biology, genetics and biochemistry, such as any functional study on a particular enzyme or cellular system, can, and probably should, involve a comparative-genomic aspect. That is, one cannot help asking: is my enzyme or system encoded in all genomes? Or only in a particular subset, say, in eukaryotes and archaea, but not in bacteria? Or is this system, with its distinct and elaborate design, present only in animals but its components can be found in yeast, archaea and bacteria where they perform other, perhaps still unknown functions? If I show that my enzyme is essential in the given organism, but is missing in others, what alternative enzyme(s) or strategies are they using? Can we predict an alternative solution from genome comparisons? Needless to say, one can obtain satisfactory answers to questions like this only by carefully comparing complete genomes. Indeed, it is hardly possible to ascertain that a particular gene is not present in the given genome unless the entire genome is available. In an ideal world, biologists should be able to address these and similar questions by querying an ‘intellectual’ database of genome comparisons. The reality is, of course, such that, although considerable systematic effort in genome comparison has been made by a number of research groups, not only does the dream query system not exist, but no one seems to have a good idea what it should look like. The absence of such a coherent system is a major problem but… it is also a research opportunity. A researcher equipped with an Internet-connected computer, a working knowledge of the sequence analysis techniques, and most importantly, a sustained interest in comparative genomics can make observations that, in many cases, are of interest and alue to a broad scientific community.