Gene duplications are often seen as an opportunity to evolve new functions through the accumulation of mutations leading to functional diversification. But, they can also be thought of as a back-up or a buffer against loss-of-function mutations in one of the duplicates. Using yeast as a working example, Gu et al. have shown that gene duplications considerably contribute to genetic robustness against null mutations.

A previous study of genetic robustness — the ability to withstand null mutations — concluded that it was redundant metabolic pathways and networks, rather than duplicate genes, that mainly fulfil this function. However, these conclusions were based only on a few genes, so Gu et al. revisited this problem — this time addressing it on a genome-wide scale. They made use of a previous study in which almost all of the genes of Saccharomyces cerevisae were knocked out and the fitness of the mutants was assessed under five different conditions (see Highlights section in September 2002 issue). When the authors compared the fitness of strains deleted for unduplicated genes with those deleted for duplicates, they found a significant difference — deletions of duplicates were significantly less likely to cause lethality and more likely to have mild effects, or no effects, under each of the five experimental conditions. These observations indicated that duplicated genes compensate for each other, a conclusion that was supported by the fact that deletions of either gene from a duplicate pair showed similar fitness effects. Furthermore, the smaller the divergence between the duplicates, the better they compensate for each other. It also turns out that deleting duplicate genes with higher expression levels has a greater effect on fitness than deleting those that are not as highly expressed.

These data provide strong evidence for the role of gene duplication in genetic robustness against null mutations. Whether this contribution is more or less important than the interactions between unduplicated genes that function in alternative pathways remains to be seen. The role of duplicates in genetic buffering might explain why these genes do not 'decay' into pseudogenes as quickly as expected. But, Axel Meyer — the author of the accompanying News and Views — suggests that their incorporation into new networks and pathways also prevents such decay. So, does this mean that we were wrong about duplications being the prerequisite for innovation? Gu et al. believe that gene duplication is still the most common path for innovation, and that a duplicate gene is maintained because it might be able either to improve part of the original function or to perform a new function. The buffering effect of duplicates is largely caused by their partially overlapping function. Axel Meyer argues for a dual role for duplicate genes, but further whole-genome-sequence comparisons and functional genetic analysis are needed before we can really address this question.