show Abstracthide AbstractSymbiosis is a ubiquitous phenomenon in nature, and these inter-species interactions have a massive impact on organisms, shaping the world around us today. The relationship between the partners in microbial symbioses have been described as existing along a parasitism-mutualism continuum, and the dynamics of this continuum are dependent upon numerous genotypic and environmental factors. Theoretical and experimental studies show that vertical transmission (VT) leads to the evolution of mutualistic traits, whereas horizontal transmission (HT) facilitates the emergence of parasitic features. However, these studies focused on phenotypic data, and we know little about underlying molecular changes at the genomic level. Here we show that a dramatic shift in the frequency of genetic variants, coupled with major changes in gene expression, allow an obligate intracellular bacterial symbiont to alter its position in the mutualism-parasitism continuum depending on the mode of between-host transmission. We found that increased virulence in horizontally transmitted chlamydiae residing in amoebae was a result of processes occurring at the infectious stage of the chlamydia's developmental cycle. Specifically, genes involved in energy production required for extracellular survival as well as the type III secretion system (T3SS) - the symbiont's primary virulence mechanism - were significantly upregulated. Our results identify the genomic and transcriptomic dynamics sufficient to favor parasitic or mutualistic strategies. Overall design: RNA-seq of Parachlamydia acanthamoebae UV-7 in Acanthamoeba sp. at 3 different time points during infection (2 hpi, 24 hpi, released elementary bodies [EBs] accumulated at 7 days post infection) for 2 experimental set-ups in triplicates; the 18 samples were sequenced on two lanes using a 50bp single read Illumina HiSeq 2500 system.