Testing the Domino Theory of Gene Loss in Buchnera aphidicola: The Relevance of Epistatic Interactions

The domino theory of gene loss states that when some particular gene loses its function and cripples a cellular function, selection will relax in all functionally related genes, which may allow for the non-functionalization and loss of these genes. Here we study the role of epistasis in determining the pattern of gene losses in a set of genes participating in cell envelope biogenesis in the endosymbiotic bacteria Buchnera aphidicola. We provide statistical evidence indicating pairs of genes in B. aphidicola showing correlated gene loss tend to have orthologs in Escherichia coli known to have alleviating epistasis. In contrast, pairs of genes in B. aphidicola not showing correlated gene loss tend to have orthologs in E. coli known to have aggravating epistasis. These results suggest that during the process of genome reduction in B. aphidicola by gene loss, positive or alleviating epistasis facilitates correlated gene losses while negative or aggravating epistasis impairs correlated gene losses. We interpret this as evidence that the reduced proteome of B. aphidicola contains less pathway redundancy and more compensatory interactions, mimicking the situation of E. coli when grown under environmental constrains.