All duplicates are not equal: the difference between small-scale and genome duplication

Abstract

Background: Genes in populations are in constant flux, being gained through duplication and occasionally retained or, more frequently, lost from the genome. In this study we compare pairs of identifiable gene duplicates generated by small-scale (predominantly single-gene) duplications with those created by a large-scale gene duplication event (whole-genome duplication) in the yeast Saccharomyces cerevisiae.

Results: We find a number of quantifiable differences between these data sets. Whole-genome duplicates tend to exhibit less profound phenotypic effects when deleted, are functionally less divergent, and are associated with a different set of functions than their small-scale duplicate counterparts. At first sight, either of these latter two features could provide a plausible mechanism by which the difference in dispensability might arise. However, we uncover no evidence suggesting that this is the case. We find that the difference in dispensability observed between the two duplicate types is limited to gene products found within protein complexes, and probably results from differences in the relative strength of the evolutionary pressures present following each type of duplication event.

Conclusion: Genes, and the proteins they specify, originating from small-scale and whole-genome duplication events differ in quantifiable ways. We infer that this is not due to their association with different functional categories; rather, it is a direct result of biases in gene retention.

Figure 1

Comparison of the shared interaction ratio for duplicate gene products and random protein pairs. Whole-genome duplicates (WGDs) are illustrated in blue and small-scale duplicates (SSDs) are illustrated in red. Mean shared interaction ratio r is plotted against gene sequence divergence measured by non-synonymous substitution rate (K_a). The dashed lines indicate the average shared interaction ratio for WGDs (blue), SSDs (red), and pairs of proteins selected at random from the genome (black). Error bars show standard errors on the mean of r for each bin.

Figure 2

Relationship between semantic distance and the proportion of pairs within each duplicate set. Whole-genome duplicates (WGDs) are illustrated in blue, small-scale duplicates (SSDs) in red, and random gene pairings in gray. A higher semantic distance indicates greater functional divergence.

Figure 3

Visualization of the two sets of duplicates on a semantic distance network. (a) The yeast proteome is distributed spatially according to semantic distance, with six high-level functional classes highlighted in different colors that are either over-represented or under-represented in the whole-genome duplicate (WGD) or small-scale duplicate (SSD) sets (see Table 1). (b) WGDs are shown in blue and SSDs in red; the same six functional classes are highlighted. The products of the two types of duplicate gene have a tendency to occupy separate areas of semantic space, indicating involvement in different functions.

Figure 4

Relationship between semantic distance, duplicate set and complex membership. The proportion of duplicate pairs having a certain level of functional divergence as measured by semantic distance for the following: pairs of complex-forming whole-genome duplicate (WGD; dark blue), complex-forming small-scale duplicate (SSD; red), non-complex-forming WGD (light blue), and non-complex-forming SSD (pink) proteins. Significant differences in the degree of functional divergence between the pairs in the two categories (complex and non-complex) are observed. No significant difference between the semantic distances of pairs of SSDs found in complexes and complex-forming WGD pairs is observed; nor, indeed, is there any difference between SSD pairs not in complexes and WGD pairs not found within complexes.