May 16, 2013
When a gene is duplicated, one copy usually dies. It is battered by harmful mutations until it eventually just fades into background DNA.
But this isn’t the fate of all duplicated genes. Sometimes they can survive by gaining new, useful functions. The genes responsible for snake venom proteins are a great example of this.
Another way for a duplicated gene to live on is when both copies get different mutations that confer different functions, so that a cell needs both to survive. Two examples of this type of codependent gene survival are highlighted in a new study by Marshall and coworkers. They compared various fungal species and identified cases where two functions were carried out by either one gene or by two separate genes. Surprisingly, these cases involve alternative mRNA splicing, which is a rare process in fungi.
The first gene pair they focused on was SKI7 and HBS1 from Saccharomyces cerevisiae. In this yeast these two genes exist as separate entities, but in other yeasts like Lachancea kluyveri they exist as a single gene which the authors have called SKI7/HBS1.
The SKI7/HBS1 gene makes two differently spliced mRNAs, each of which encodes a protein that matches up with either Ski7p or Hbs1p. In addition, the SKI7/HBS1 gene can rescue a S. cerevisiae strain missing either or both the SKI7 and HBS1 genes. Taken together, this is compelling evidence that SKI7 and HBS1 existed as a single gene in the ancestor of these two fungal species. In S. cerevisiae, after this gene was duplicated each copy lost the ability to produce one spliced form.
The second gene Marshall and coworkers looked at experienced the reverse situation during evolution. PTC7 exists as a single gene that makes two mRNA isoforms in S. cerevisiae: an unspliced form that generates a nuclear-localized protein, and a spliced form that produces a mitochondrial protein.
But in Tetrapisispara blattae, these two forms exist as separate genes. The PTC7a gene is similar to the unspliced form in S. cerevisiae and the protein ends up in the nucleus, while the PTC7b gene is similar to the spliced S. cerevisiae version and its product is mitochondrial.
Because an ancestor of S. cerevisiae had every one of its genes duplicated about 100 million years ago, yeasts have been a great system to study the fate of duplicated genes. This study shows that even though gene duplication is widespread in fungi and alternative splicing is rare, these mechanisms are actually interrelated and each can increase the diversity of the proteins produced by a species.
Fun fact: 544 genes survived duplication in S. cerevisiae. That is around 10%.
by D. Barry Starr, Ph.D., Director of Outreach Activities, Stanford Genetics
Categories: Research Spotlight