Zürich, Switzerland – When Mother Nature creates an identicalcopy of a gene in an organism's genome, the duplicated copy is usuallydeleted, inactivated, or otherwise rendered nonfunctional in order toprevent genetic redundancy and to preserve biological homeostasis. Insome cases, however, gene duplicates are maintained in a functionalstate. Until now, the biological and evolutionary forces behind themaintenance of these duplicates as functional components of the genomehave remained unclear.
To determine the basis for the persistenceof functional gene duplicates in the genome, three scientists at theInstitute of Molecular Systems Biology at the Swiss Federal Instituteof Technology in Zürich have collaborated on the largest systematicanalysis of duplicated gene function to date. Using an integrativecombination of computational and experimental approaches, theyclassified duplicate pairs of genes involved in yeast metabolism intofour functional categories: (1) back-up, where a duplicate gene copyhas acquired the ability to compensate in the absence of the othercopy, (2) subfunctionalization, where a duplicate copy has evolved acompletely new, non-overlapping function, (3) regulation, where thedifferential regulation of duplicates fine-tunes pathway usage, and (4)gene dosage, where the increased expression provided by the duplicategene copy augments production of the corresponding protein.
Theirresults, which appear in the October issue of the journal GenomeResearch, indicate that no single role prevails but that all four ofthe mechanisms play a substantial role in maintaining duplicate genesin the genome.
"Our results contradict other recent publicationsthat have focused on a single selective pressure as the basis for theretention of gene duplicates," explains Dr. Uwe Sauer, principalinvestigator on the project and Professor at the Institute of MolecularSystems Biology at the Swiss Federal Institute of Technology in Zürich."We show that, at least for yeast metabolism, the persistence of theduplicated fraction of the genome can be better explained with an arrayof different, often overlapping functional roles."
Yeastmetabolism provides an ideal model for investigating the functionalbasis for gene duplication because a large proportion of genes involvedin this biological process have been duplicated. Of the 672 genesinvolved in yeast metabolism, 295 genes can be classified into 105families of duplicates. To put this into perspective, the yeast genomehas an estimated total of 6,000 genes, 1,500 of which are considered tobe duplicates. An ancient whole-genome duplication event is thought tobe responsible for the formation of many of these duplicate copies.
Sauer'sgroup demonstrated that of the 105 families of duplicated gene familiesinvolved in yeast metabolism, 34 demonstrated back-up function, 19 wereinvolved in increased gene dosage, 18 exhibited regulatory functions,and 18 had evolved new, more specialized functions. Therefore, each ofthese mechanisms plays a substantial and important role in themaintenance of functional duplicates in the gene pool.
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