From Genetics this week a review discusses Why are there still 1000 Uncharacterized Yeast genes? Poor Yeast – so many more genes have no known function, while S. pombe has nearly 100% coverage in functional annotation. I’ll also point out that the 1000 genes refers to protein-coding genes, not ncRNA genes which may mean that there is alot more that is unknown.
I think this sentence from the abstract hits the nail on the head.
Notably,the uncharacterized gene set is highly enriched for genes whose only homologs are in other fungi. Achieving a full catalog of yeast gene functions may require a greater focus on the life of yeast outside the laboratory.
There are certainly a lot of genes that are fungal specific and have no known function. Perhaps only by working at these genes in different fungal systems will we be able to discover their function. It may be the case that yeast itsself will be a poor model for understanding these genes and it will require forward genetics in a different fungal model to understand and assign a functional role for them.
I also think a lot of important work is being done to look at the consequence of alleles of genes in different backgrounds by trying to map QTLs for complex traits like high temperature growth in S. cerevisiae obtained from immunocompromised individuals. This way we are able to discover a gene’s function without having look at it in a null background, but rather (if we can) dissect the genes underlying a QTL we might find a more subtle understanding of genotype-phenotype relationship. Perhaps only in this way by taking strains with different phenotypes under a particular condition (e.g. resistance to oxidative stress, carbon utilization efficiency), crossing those with low and high traits, and mapping the genes we might learn about genes’ functions that would never be found in a reverse genetics screen.