Why are there still over 1000 uncharacterized yeast genes?

Abstract

The yeast genetics community has embraced genomic biology, and there is a general understanding that obtaining a full encyclopedia of functions of the approximately 6000 genes is a worthwhile goal. The yeast literature comprises over 40,000 research papers, and the number of yeast researchers exceeds the number of genes. There are mutated and tagged alleles for virtually every gene, and hundreds of high-throughput data sets and computational analyses have been described. Why, then, are there >1000 genes still listed as uncharacterized on the Saccharomyces Genome Database, 10 years after sequencing the genome of this powerful model organism? Examination of the currently uncharacterized gene set suggests that while some are small or newly discovered, the vast majority were evident from the initial genome sequence. Most are present in multiple genomics data sets, which may provide clues to function. In addition, roughly half contain recognizable protein domains, and many of these suggest specific metabolic activities. 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.

Figure 1.—

Distribution of ORFs in “dubious,” “uncharacterized,” and “verified” as classified by SGD since October 2003.

Figure 2.—

Properties of uncharacterized yeast genes. Information from supplemental data of the articles indicated (Velculescu et al. 1997; Blandin et al. 2000; Giaever et al. 2002; Kumar et al. 2002; Oshiro et al. 2002; Brachat et al. 2003; Cliften et al. 2003; Kellis et al. 2003; Kessler et al. 2003; Gavin et al. 2006; Kastenmayer et al. 2006; Krogan et al. 2006; Miura et al. 2006; Nishida 2006; Stark et al. 2006).

Figure 3.—

Uncharacterized vs. verified ORFs expression as mRNA (Velculescu et al. 1997) and protein (Ghaemmaghami et al. 2003).

Figure 4.—

Redundant uncharacterized ORFs. The heat map shows the percentage of identical sequence among 161 uncharacterized ORFs (the same ordering is used on both axes).

Figure 5.—

Potential function or functionality for 1253 uncharacterized yeast genes.