Testing the Domino Theory of Gene Loss in : 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 . We provide statistical evidence indicating pairs of genes in . showing correlated gene loss tend to have orthologs in known to have alleviating epistasis. In contrast, pairs of genes in . not showing correlated gene loss tend to have orthologs in . known to have aggravating epistasis. These results suggest that during the process of genome reduction in . 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 . contains less pathway redundancy and more compensatory interactions, mimicking the situation of . when grown under environmental constrains.