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The dark side

DOI: 10.1186/gb-2000-1-3-comment1003

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Abstract:

We will all face the dark side before long, as the emphasis in genomics shifts from identifying and sequencing genes to the problem of determining what their products do. Leaving aside the formidable technical challenges posed by that problem, there remains the prospect that the job, as commonly considered, is impossible: because the term 'function' means very different things to different people, and a given gene product might have almost as many 'functions' as there are scientists studying it. There is its biochemical function: the chemical or physical process it carries out when isolated from the cell and studied in vitro. There is its cellular function - signal transduction protein, translation inhibitor, transcription factor, and so on - which may depend on its location in the cell, what other molecules it is bound to, when in the cell cycle it is expressed, and so on. Then there is its larger biological function, which is most often defined by the pheno-type that is observed when it is deleted or mutated: growth control, or immune regulation, or involvement in morpho-genesis, to name but a few possibilities. The layers are almost infinite, especially for genes in metazoan organisms.Consider actin. Its biochemical function is to bind ATP and hydrolyse it, but it is not very good at that on its own. The ATPase activity can be modulated by the binding of other molecules - a common phenomenon in biochemistry. One could also say that the 'real' function of actin is to self-polymerize, forming filaments. This brings us closer to the cellular roles of actin, but these are legion: essential component of the cytoskeleton, 'railroad track' along which vesicles and other cellular constituents run, anchor for myosin in muscle contraction, target for the mushroom toxin phalloidin, rigidifier of microvilli, backbone of the acrosome, inhibitor of DNase I, and many more. When can we say we know what the 'function' of the actin gene is?Clearly any attempt to understand functio

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