Lineage-specific loss and divergence of functionally linked genes in eukaryotes

Abstract

By comparing 4,344 protein sequences from fission yeast Schizosaccharomyces pombe with all available eukaryotic sequences, we identified those genes that are conserved in S. pombe and nonfungal eukaryotes but are missing or highly diverged in the baker's yeast Saccharomyces cerevisiae. Since the radiation from the common ancestor with S. pombe, S. cerevisiae appears to have lost about 300 genes, and about 300 more genes have diverged by far beyond expectation. The most notable feature of the set of genes lost in S. cerevisiae is the coelimination of functionally connected groups of proteins, such as the signalosome and the spliceosome components. We predict similar coelimination of the components of the posttranscriptional gene-silencing system that includes the recently identified RNA-dependent RNA polymerase. Because one of the functions of posttranscriptional silencing appears to be "taming" of retrotransposons, the loss of this system in yeast could have triggered massive retrotransposition, resulting in elimination of introns and subsequent loss of spliceosome components that become dispensable. As the genome database grows, systematic analysis of coordinated gene loss may become a general approach for predicting new components of functional systems or even defining previously unknown functional complexes.

Figure 1

The protocol for detecting candidates for gene loss and divergence in S. cerevisiae. nrify is a program in the SEALS package that is used to generate a nonredundant protein database.

Figure 2

Scatter plots of sequence similarity between S. pombe proteins and their homologs from S. cerevisiae, plants, and animals. Horizontal axis: −log₁₀[E value (S. pombe with S. cerevisiae)]. Vertical axis: log₁₀[E-value (S. pombe with S. cerevisiae)] − log₁₀ [E-value (S. pombe with nonfungal eukaryote)]. The thick, horizontal line indicates the 10 orders of magnitude threshold used to delineate the set of anomalous hits that were analyzed further for likely cases of gene loss and divergence. (A) Metazoa vs. S. cerevisiae. (B) Plants vs. S. cerevisiae

Figure 3

Selected phylogenetic trees for protein families with apparent loss of paralogs in S. cerevisiae. (A) Cullins. (B) Cyclins (two cases of gene loss in S. cerevisiae). (C) Rab-type GTPase. (D) Kinesin ATPase subunit. (E) ABC transporter ATPase subunit. (F) DinB family of DNA repair polymerases. Circles denote nodes with at least 70% bootstrap support. The proteins are designated by their gene identifiers (GI numbers) in the nonredundant database and species abbreviations: Sc, S. cerevisiae; Sp, S. pombe; Nc, Neurospora crassa; Um, Ustilago maydis; Dm, D. melanogaster; Ce, C. elegans; Hs, Homo sapiens; Xl, Xenopus laevis; At, Arabidopsis thaliana; Os, Oryza sativa. Proteins from S. cerevisiae are color-coded blue, and those from S. pombe are coded red.

Figure 4

The extent of apparent gene loss in different functional categories of S. cerevisiae genes. Three types of evolutionary events, namely, complete elimination of a gene family, with no detectable S. cerevisiae homolog for a S. pombe protein (Bottom, purple area in each bar), elimination of a paralog (Middle, dark-red area), and anomalous divergence (Top, yellow area) are shown for different functional classes of S. cerevisiae genes. Vertical axis, number of genes. ER, endoplasmic reticulum.