Change with a purpose

Change with a purpose Evolution depends on mutations - changes in the sequence or organisation of DNA (the hereditar material). Mutation is the ultimate source of genetic variability. One of the cardinal tenets of the theory of evolution by natural selection - Darwinism - states that mutations occur at random., Here, 'random' stands for 'non-purposive: the likelihood of a particular mutation occurring bears no relation to whether that mutation will be beneficial or not.

This supposition has come under fire in recent years with the suggestion (based on a very small number of experiments) that mutations tend to occur with a higher-than-average probability when they are advantageous, than when they are disadvantageous. However, this claim has not been backed up by an explanation of how such apparently 'directed' mutations might come about. Recent work by Qing Lu and colleagues at the R W Johnson Medical School, New Jersey, usA, offers the first step towards a possible answer (Journal of Molecular Biology, Vol 254, 1995).

It is a first step because what the study shows is that an imbalance in the levels of certain cellular metabolites can cause an increase in mutation rates; it does not demonstrate a specific increase in rates in those genes that might redress the imbalance. Lu's group studied the consequences of disrupting the gene that encodes an enzyme called NDP (nucleoside diphosphate) kinase in the common intestinal bacterium Escherichia coli. NDP kinase maintains the internal balance between di and triphosphates of sugars complexed with the common bases adenine, guanine, cytosine and thymine. This means that NDP kinase is a crucial enzyme, because these four bases, taken three at a time, constitute the elementary 'words' of the genetic code in the DNA molecule.

The outcome qf the disruption was surprising in two respects. Firstly, the gene for NDP kinase appeared to be dispensable; there was no visible effect following its disruption. This showed that there are besides the one catalysed by the NDP kinase.

The second, and more striking, surprise was that closer examination revealed a subtle effect of the disruption after all. The disrupted gene caused the bacterium to behave as a 'mutator'; it started mutating at a 20- to 50-fold higher rate than the parental strain. A reason for this could be the aberrant nucleoside triphosphate levels found in the disrupted strain.

Now, if mutations are to be directed, it is necessary that the demands made by the environment be conveyed directly to the genome. The nucleosides and their phosphates are products of normal metabolism and their ultimate source is food. Therefore, their levels can be affected by 'environmental' factors, like stress for instance. Does a similar response to the one found by Lu and co-workers in E coli occur in humans and other higher animals? If so, it would imply that a stressful environment can elicit a response which indicates an attempt on the part of the organism to relieve the stress genetically by mutating to an alternative state.

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