Functional diversification of duplicate genes through subcellular adaptation of encoded proteins

Abstract

Background: Gene duplication is the primary source of new genes with novel or altered functions. It is known that duplicates may obtain these new functional roles by evolving divergent expression patterns and/or protein functions after the duplication event. Here, using yeast (Saccharomyces cerevisiae) as a model organism, we investigate a previously little considered mode for the functional diversification of duplicate genes: subcellular adaptation of encoded proteins.

Results: We show that for 24-37% of duplicate gene pairs derived from the S. cerevisiae whole-genome duplication event, the two members of the pair encode proteins that localize to distinct subcellular compartments. The propensity of yeast duplicate genes to evolve new localization patterns depends to a large extent on the biological function of their progenitor genes. Proteins involved in processes with a wider subcellular distribution (for example, catabolism) frequently evolved new protein localization patterns after duplication, whereas duplicate proteins limited to a smaller number of organelles (for example, highly expressed biosynthesis/housekeeping proteins with a slow rate of evolution) rarely relocate within the cell. Paralogous proteins evolved divergent localization patterns by partitioning of ancestral localizations ('sublocalization'), but probably more frequently by relocalization to new compartments ('neolocalization'). We show that such subcellular reprogramming may occur through selectively driven substitutions in protein targeting sequences. Notably, our data also reveal that relocated proteins functionally adapted to their new subcellular environments and evolved new functional roles through changes of their physico-chemical properties, expression levels, and interaction partners.

Conclusion: We conclude that protein subcellular adaptation represents a common mechanism for the functional diversification of duplicate genes.

Figure 1

Distribution of non-synonymous substitution rates (d_N) for duplicate genes in S- and D-pairs (estimated for the time since the whole-genome duplication event - see text for details).

Figure 2

Illustration of the different evolutionary fates of (functional) duplicate genes. Each gene/protein is represented in different colors: red, ancestral, 'A'; green, duplicate copy A1; and blue, duplicate copy A2. Different shapes of proteins (circle, square, and triangle) indicate different functions. Three different subcellular localizations (nucleus, cytoplasm, and cytoplasmic membrane) are indicated in a schematic cell. We note that only the major possible scenarios are illustrated here.

Figure 3

Subcellular localizations of the (a) UBC and (b) AIR family members and subcellular localization changes inferred based on the phylogeny. The common name and yeast protein identifier (in brackets) of the protein are indicated. The schematic representation of a yeast cell depicts three possible localizations: nucleus (small circle), endoplasmatic reticulum (eclipse around nucleus), and cytoplasm (remainder of the cell). The co-localization of the protein with one of the yeast subcellular compartments is indicated by grey shading.

Figure 4

Subcellular relocalization and signal peptide evolution. Signal peptides (36 amino-terminal residues) and experimentally determined subcellular localizations of the (a) NTG1/NTG2 and (b) TRR1/TRR2 duplicate pairs (derived from the S. cerevisiae WGD event) are shown. K. waltii orthologous sequences are used as outgroups. Predotar [39,40] was used to predict subcellular localizations based on the protein sequences. The (predicted) subcellular localization of the K. waltii proteins was considered to represent the ancestral state. Identical residues in all peptide sequences are represented with (*) under the corresponding position in the protein alignment.

Figure 5

Distribution of the proportion of shared interactors for genes in S- and D-pairs.