Phagocytosis and autophagy are cellular mechanisms that recognize and eliminate pathogens from the extracellular space and cellular interior, respectively. These mechanisms, as a part of the immune system, defend the host from a wide range of ever-changing pathogens that evolve to escape, resist or compromise host immunity. Some bacteria use effector proteins that manipulate host autophagy and phagocytosis to either inhibit immune defense or to promote bacterial invasion into the interior of the cell. In response, the host may experience selective pressure to adapt. This dynamic conflict may result in coevolution, leading to recurrent positive directional selection on host genes. Therefore, we hypothesize that host phagocytosis and autophagy genes may have experienced more positive selection than other genes in the genome. We specifically hypothesize that genes that are known to interact with bacterial factors are most likely to have undergone positive selection.
To test this hypothesis, we perform population genetic analyses on a curated set of phagocytosis and autophagy genes, as well as control genes that are matched with case genes by gene length and genome location, using 197 Drosophila melanogaster sequences from the Drosophila Genome Nexus Project. Initial analyses suggest strong, recent selection on a subset of autophagy genes, including Atg8a and Atg13. Atg8a is known to be involved in the expansion of autophagosome, while Atg13 is involved in autophagosome induction. Previous work has shown that an effector protein from the intracellular pathogen Legionella pneumophila inhibits host autophagy by blocking the proper conjugation of Atg8a with Atg3 and Atg7, supporting our hypothesis that Atg8a may be a target of host-pathogen coevolution. This is the first study to examine the evolution of non-receptor phagocytosis and autophagy genes involved in immune defense and will provide a novel insight into the evolution of the innate immune responses.