Largest systematic analysis of duplicated gene function to date

When Mother Nature creates an identical copy of a gene in an organism's genome, the duplicated copy is usually deleted, inactivated, or otherwise rendered nonfunctional in order to prevent genetic redundancy and to preserve biological homeostasis. In some cases, however, gene duplicates are maintained in a functional state. Until now, the biological and evolutionary forces behind the maintenance of these duplicates as functional components of the genome have remained unclear.

To determine the basis for the persistence of functional gene duplicates in the genome, three scientists at the Institute of Molecular Systems Biology at the Swiss Federal Institute of Technology in Zürich have collaborated on the largest systematic analysis of duplicated gene function to date. Using an integrative combination of computational and experimental approaches, they classified duplicate pairs of genes involved in yeast metabolism into four functional categories:

1. back-up, where a duplicate gene copy has acquired the ability to compensate in the absence of the other copy,
2. subfunctionalization, where a duplicate copy has evolved a completely new, non-overlapping function,
3. regulation, where the differential regulation of duplicates fine-tunes pathway usage, and
4. gene dosage, where the increased expression provided by the duplicate gene copy augments production of the corresponding protein.

Their results, which appear in the October issue of the journal Genome Research, indicate that no single role prevails but that all four of the mechanisms play a substantial role in maintaining duplicate genes in the genome.

"Our results contradict other recent publications that have focused on a single selective pressure as the basis for the retention of gene duplicates," explains Dr. Uwe Sauer, principal investigator on the project and Professor at the Institute of Molecular Systems Biology at the Swiss Federal Institute of Technology in Zürich. "We show that, at least for yeast metabolism, the persistence of the duplicated fraction of the genome can be better explained with an array of different, often overlapping functional roles."

Yeast metabolism provides an ideal model for investigating the functional basis for gene duplication because a large proportion of genes involved in this biological process have been duplicated. Of the 672 genes involved in yeast metabolism, 295 genes can be classified into 105 families of duplicates. To put this into perspective, the yeast genome has an estimated total of 6,000 genes, 1,500 of which are considered to be duplicates. An ancient whole-genome duplication event is thought to be responsible for the formation of many of these duplicate copies.

Sauer's group demonstrated that of the 105 families of duplicated gene families involved in yeast metabolism, 34 demonstrated back-up function, 19 were involved in increased gene dosage, 18 exhibited regulatory functions, and 18 had evolved new, more specialized functions. Therefore, each of these mechanisms plays a substantial and important role in the maintenance of functional duplicates in the gene pool.