Abstract
BackgroundSelective gene duplicability, the extensive expansion of a small number of gene families, is universal. Quantitatively, the number of genes (P(K)) with K duplicates in a genome decreases precipitously as K increases, and often follows a power law (P(k)∝k-α). Functional diversification, either neo- or sub-functionalization, is a major evolution route for duplicate genes.ResultsUsing three lines of genomic datasets, we studied the relationship between gene duplicability and diversifiability in the topology of biochemical networks. First, we explored scenario where two pathways in the biochemical networks antagonize each other. Synthetic knockout of respective genes for the two pathways rescues the phenotypic defects of each individual knockout. We identified duplicate gene pairs with sufficient divergences that represent this antagonism relationship in the yeast S. cerevisiae. Such pairs overwhelmingly belong to large gene families, thus tend to have high duplicability. Second, we used distances between proteins of duplicate genes in the protein interaction network as a metric of their diversification. The higher a gene’s duplicate count, the further the proteins of this gene and its duplicates drift away from one another in the networks, which is especially true for genetically antagonizing duplicate genes. Third, we computed a sequence-homology-based clustering coefficient to quantify sequence diversifiability among duplicate genes – the lower the coefficient, the more the sequences have diverged. Duplicate count (K) of a gene is negatively correlated to the clustering coefficient of its duplicates, suggesting that gene duplicability is related to the extent of sequence divergence within the duplicate gene family.ConclusionThus, a positive correlation exists between gene diversifiability and duplicability in the context of biochemical networks – an improvement of our understanding of gene duplicability.
Highlights
Selective gene duplicability, the extensive expansion of a small number of gene families, is universal
We performed respective all-against-all BLAST for protein sequences encoded in the yeast S. cerevisiae and the human genome, with a threshold E-value of 10−30
Pairs of duplicate genes that have diverged to mutual genetic antagonism tend to belong to high duplicability gene families We looked for an approach to identify cases of high diversifiability among duplicate genes, so that we could determine whether high diversifiability is associated with high gene duplicability, i.e., high K values
Summary
The extensive expansion of a small number of gene families, is universal. Genomic duplication is a major driving force of biological evolution [6,7,8]. Proteins of duplicate genes are abundant in biochemical networks Their abundance increases along with genomic complexity, which is quantified by genome size, gene number, abundance of spliceosomal introns and mobile genetic elements, from bacterial to unicellular eukaryotes, to multi-cellular species [9]. Proteins of duplicate genes function and evolve in biochemical networks [10,11]. Duplicate gene evolution is frequently analyzed in the context of biochemical networks, such as the protein-protein interaction networks [12,13,14] and the metabolic networks [15,16], as well as other biological networks [17,18]
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