The overall goal of the proposed research is to develop the genetic theory necessary for understanding how patterns of co-transmission of host and microbial genomes affect the co-evolution of symbiotic and pathogenic bacteria with their hosts. Our approach is novel in that it extends theory developed for modeling the inheritance of nuclear gene combinations within single genomes to gene combinations across two genomes, those of host and pathogen. When applied to nuclear and mitochondrial gene combinations, this approach successfully predicted the frequency of functional gene transfer from the mitochondria to the nucleus: inter-genomic transfer of functional genes is ten-fold more likely to occur in inbreeding species than in outcrossing species. The reason for this effect of mating system on gene transfer is that mating systems, where mitochondrial and nuclear genes are inherited together, allow natural selection to act more effectively on gene combinations than mating systems where the genes are inherited independently. Although mitochondria are wholly vertically transmitted like some endosymbionts, similar effects are expected to be manifest in systems with only partial vertical transmission and we will develop this more general theory. Two-locus descent theory quantifies the coinheritance of gene combinations in the same or different genomes, determining the degree to which the evolutionary trajectories of genes in each species are conjoined. This determines whether a host-pathogen association will develop toward enhanced virulence or toward benign symbiosis. Project Narrative: Change in the dispersal rates fundamentally change the genetic coevolution both hosts and their pathogens and contribute to the emergence of new diseases. Although a direct link between dispersal of infected hosts and disease epidemiology within a single host generation is well known, the genetic consequences of disease transmission from one generation of hosts to the next is much more poorly understood. This proposal will develop genetic theory for addressing how the co-inheritance of host genes and host pathogens affects the evolution of disease virulence.