Did the early full genome sequencing of yeast boost gene function discovery?

BACKGROUND: Although the genome of Saccharomyces cerevisiae (S. cerevisiae) was the first one of a eukaryote organism that was fully sequenced (in 1996), a complete understanding of the potential of encoded biomolecular mechanisms has not yet been achieved. Here, we wish to quantify how far the goal of a full list of S. cerevisiae gene functions still is. RESULTS: The scientific literature about S. cerevisiae protein-coding genes has been mapped onto the yeast genome via the mentioning of names for genomic regions in scientific publications. The match was quantified with the ratio of a given gene name's occurrences to those of any gene names in the article. We find that ~ 230 elite genes with ≥ 75 full publication equivalents (FPEs, FPE = 1 is an idealized publication referring to just a single gene) command ~ 45% of all literature. At the same time, about two thirds of the genes (each with less than 10 FPEs) are described in just 12% of the literature (in average each such gene has just ~ 1.5% of the literature of an elite gene). About 600 genes have not been mentioned in any dedicated article. Compared with other groups of genes, the literature growth rates were highest for uncharacterized or understudied genes until late nineties of the twentieth century. Yet, these growth rates deteriorated and became negative thereafter. Thus, yeast function discovery for previously uncharacterized genes has returned to the level of ~ 1980. At the same time, literature for anyhow well-studied genes (with a threshold T10 (≥ 10 FPEs) and higher) remains steadily growing. CONCLUSIONS: Did the early full genome sequencing of yeast boost gene function discovery? The data proves that the moment of publishing the full genome in reality coincides with the onset of decline of gene function discovery for previously uncharacterized genes. If the current status of literature about yeast molecular mechanisms can be extrapolated into the future, it will take about another ~ 50 years to complete the yeast gene function list. We found that a small group of scientific journals contributed extraordinarily to publishing early reports relevant to yeast gene function discoveries.

About the dark corners in the gene function space of Escherichia coli remaining without illumination by scientific literature.

BACKGROUND: Although Escherichia coli (E. coli) is the most studied prokaryote organism in the history of life sciences, many molecular mechanisms and gene functions encoded in its genome remain to be discovered. This work aims at quantifying the illumination of the E. coli gene function space by the scientific literature and how close we are towards the goal of a complete list of E. coli gene functions. RESULTS: The scientific literature about E. coli protein-coding genes has been mapped onto the genome via the mentioning of names for genomic regions in scientific articles both for the case of the strain K-12 MG1655 as well as for the 95%-threshold softcore genome of 1324 E. coli strains with known complete genome. The article match was quantified with the ratio of a given gene name's occurrence to the mentioning of any gene names in the paper. The various genome regions have an extremely uneven literature coverage. A group of elite genes with ≥ 100 full publication equivalents (FPEs, FPE = 1 is an idealized publication devoted to just a single gene) attracts the lion share of the papers. For K-12, ~ 65% of the literature covers just 342 elite genes; for the softcore genome, ~ 68% of the FPEs is about only 342 elite gene families (GFs). We also find that most genes/GFs have at least one mentioning in a dedicated scientific article (with the exception of at least 137 protein-coding transcripts for K-12 and 26 GFs from the softcore genome). Whereas the literature growth rates were highest for uncharacterized or understudied genes until 2005-2010 compared with other groups of genes, they became negative thereafter. At the same time, literature for anyhow well-studied genes started to grow explosively with threshold T10 (≥ 10 FPEs). Typically, a body of ~ 20 actual articles generated over ~ 15 years of research effort was necessary to reach T10. Lineage-specific co-occurrence analysis of genes belonging to the accessory genome of E. coli together with genomic co-localization and sequence-analytic exploration hints previously completely uncharacterized genes yahV and yddL being associated with osmotic stress response/motility mechanisms. CONCLUSION: If the numbers of scientific articles about uncharacterized and understudied genes remain at least at present levels, full gene function lists for the strain K-12 MG1655 and the E. coli softcore genome are in reach within the next 25-30 years. Once the literature body for a gene crosses 10 FPEs, most of the critical fundamental research risk appears overcome and steady incremental research becomes possible.