A scale of functional divergence for yeast duplicated genes revealed from analysis of the protein-protein interaction network

Abstract

Background: Studying the evolution of the function of duplicated genes usually implies an estimation of the extent of functional conservation/divergence between duplicates from comparison of actual sequences. This only reveals the possible molecular function of genes without taking into account their cellular function(s). We took into consideration this latter dimension of gene function to approach the functional evolution of duplicated genes by analyzing the protein-protein interaction network in which their products are involved. For this, we derived a functional classification of the proteins using PRODISTIN, a bioinformatics method allowing comparison of protein function. Our work focused on the duplicated yeast genes, remnants of an ancient whole-genome duplication.

Results: Starting from 4,143 interactions, we analyzed 41 duplicated protein pairs with the PRODISTIN method. We showed that duplicated pairs behaved differently in the classification with respect to their interactors. The different observed behaviors allowed us to propose a functional scale of conservation/divergence for the duplicated genes, based on interaction data. By comparing our results to the functional information carried by GO annotations and sequence comparisons, we showed that the interaction network analysis reveals functional subtleties, which are not discernible by other means. Finally, we interpreted our results in terms of evolutionary scenarios.

Conclusions: Our analysis might provide a new way to analyse the functional evolution of duplicated genes and constitutes the first attempt of protein function evolutionary comparisons based on protein-protein interactions.

Figure 1

Distribution of functional distances between duplicated pairs based on Gene Ontology annotations. The annnotations are for 'Biological Process' (blue), 'Molecular Function' (purple) and 'Cellular Component' (light yellow). Distributions of distances (ranging from 0 to 1) based on annotations for (a) the 460 duplicated pairs, (a, inset) randomly selected pairs and (b) the 41 duplicated pairs present in the PRODISTIN tree.

Figure 2

PRODISTIN classification tree for 890 yeast proteins. PRODISTIN classes have been colored according to their corresponding Biological Process annotations. Protein names have been omitted for clarity. The tree contains 41 out of 460 duplicated pairs, the remnant of the ancient whole-genome duplication. Examples of PRODISTIN classes illustrating the three different behaviors of duplicated pairs have been extracted and enlarged from the tree. Their original position in the tree is shown by dashed lines.

Figure 3

Repartition of the 3 different PRODISTIN behaviors in respect to the distribution of the GO-based functional distances (ranging from 0 to 1) between the 41 duplicated pairs. Behaviors are classified as: same class, same function (behavior I, blue); different classes, same function (behavior II, pink); different classes, different functions (behavior III, gray); not classified (green). Results are shown for the Biological Process annotations only.

Figure 4

Percent of sequence identity between the 41 duplicated protein pairs. Proteins were classified as belonging to the same class (blue diamonds), different classes with the same function (pink diamonds), different classes with different functions (gray diamonds), or not classified (green triangles).