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 <italic>Buchnera aphidicola</italic>. We provide statistical evidence indicating pairs of genes in <italic>B</italic>. <italic>aphidicola</italic> showing correlated gene loss tend to have orthologs in <italic>Escherichia coli</italic> known to have alleviating epistasis. In contrast, pairs of genes in <italic>B</italic>. <italic>aphidicola</italic> not showing correlated gene loss tend to have orthologs in <italic>E</italic>. <italic>coli</italic> known to have aggravating epistasis. These results suggest that during the process of genome reduction in <italic>B</italic>. <italic>aphidicola</italic> 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 <italic>B</italic>. <italic>aphidicola</italic> contains less pathway redundancy and more compensatory interactions, mimicking the situation of <italic>E</italic>. <italic>coli</italic> when grown under environmental constrains. [ABSTRACT FROM AUTHOR]