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Yeast fitness and protein evolution

DOI: 10.1186/gb-2001-2-9-reports0030

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Hirsh and Fraser obtained reliable estimates of fitness for 548 homozygous single-gene deletants. The evolutionary distances di (number of substitutions per amino acid site) could be estimated for 119 mutants out of the 548 using two different methods. They found a statistically significant relationship between di and fi, showing that proteins with a lower fitness effect are more divergent. But, the di values represent evolutionary change not only in the yeast sequences but also in the corresponding nematode orthologs. To estimate evolutionary change only in the lineage leading to yeast, di measures were split into two components, one between yeast and the hypothetical most recent common ancestor (MRCA) of fungi and animals and another between the MRCA and C. elegans: the outgroup sequences were orthologs present in other completely sequenced genomes. Hirsh and Fraser analyzed 48 yeast proteins in this way and again a significant relationship between fi and the 'new' di values was obtained. Most interestingly, statistically significant results were obtained when they plotted fi (from yeast) against the di between the MRCA and the nematode. This suggests that non-essential proteins that have an impact on the fitness of yeast might also have a proportional effect on worm fitness. No differences were detected when the essential genes were subject to the same analysis and compared with the non-essential ones, which is consistent with the results of analyses in mouse. When the comparison was carried out against the most dispensable 60 proteins (smallest fi values), however, a highly significant difference was detected.This work provides the long awaited (at least preliminary) confirmation of a fundamental prediction about protein evolution. It is an example of how genomic data can be exploited from different perspectives to address important biological questions. In fact, the starting point of the present study was the results of a high-throughput parallel analysis of ye


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