Theoretical Understanding of Target Search Dynamics in Horizontal Gene Transfer in Bacteria

Abstract

Horizontal gene transfer (HGT) is a fundamental process of increasing genetic diversity in microbial species. It allows bacterial cells to acquire new beneficial traits quickly by incorporating new genetic material into existing genomes. Despite the critical importance of HGT phenomena, the underlying molecular mechanisms are still poorly understood. Recent experiments investigated the dynamics of conjugation HGT processes in which DNA is transmitted directly from the donor to the recipient bacterial cell. It is accomplished by special mobile genetic particles known as integrative and conjugative elements (ICE). However, the molecular picture of how ICE can efficiently find the unique integration sites in a new genome is not yet clear. We present a novel theoretical model to explain the dynamic processes in HGT after ICE reaches the recipient cell. It is shown that the target search for integration sites can be viewed as a set of stochastic transitions between discrete states, allowing us to obtain an explicit description of the dynamic properties using analytical calculations supported by Monte Carlo computer simulations. Search times are found to depend on the location of integration sites, the size of the genome, the effective diffusion rate of mobile genetic elements, and the binding/unbinding transitions between ICE and DNA. Theoretical estimates for search times agree well with experimental observations for integration in Bacillus subtilis bacterial species. Physical-chemical arguments are presented to explain the dynamics of the ICE target search. This study clarifies some important mechanistic aspects of HGT phenomena.