Transmission bottlenecks as determinants of virulence in rapidly evolving pathogens

Transmission bottlenecks occur in pathogen populations when only a few indi vidual pathogens are transmitted from one infected host to another in the i nitiation of a new infection. Transmission bottlenecks can dramatically aff ect the evolution of virulence in rapidly evolving pathogens such as RNA vi ruses. Characterizing pathogen diversity with the quasispecies concept, we use analytical and simulation methods to demonstrate that severe bottleneck s are likely to drive dean the virulence of a pathogen because of stochasti c loss of the most virulent pathotypes, through a process analogous to Mull er's ratchet. We investigate in this process the roles of host population s ize, duration of within-host viral replication, and transmission bottleneck size. We argue that the patterns of accumulation of deleterious mutation m ay explain differing levels of virulence in vertically and horizontally tra nsmitted diseases.