title: Pathogen population bottlenecks and adaptive landscapes: overcoming the barriers to disease emergence.
abstract: Emerging diseases are a major challenge to public health. Revealing the evolutionary processes that allow novel pathogens to adapt to new hosts, also the potential barriers to host adaptation, is central to understanding the drivers of disease emergence. In particular, it is unclear how the genetics and ecology of pathogens interact to shape the likelihood of successful cross-species transmission. To better understand the determinants of host adaptation and emergence, we modelled key aspects of pathogen evolutionary dynamics at both intra- and inter-host scales, using parameter values similar to those observed in influenza virus. We considered the possibility of acquiring the necessary host adaptive mutations both before ('off-the-shelf' emergence) and after ('tailor-made' emergence) a virus is transmitted from a donor to a new recipient species. Under both scenarios, population bottlenecks at inter-host transmission act as a major barrier to host adaptation, greatly limiting the number of adaptive mutations that are able to cross the species barrier. In addition, virus emergence is hindered if the fitness valley between the donor and recipient hosts is either too steep or too shallow. Overall, our results reveal where in evolutionary parameter space a virus could adapt to and become transmissible in a new species.
authors: Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Life and Environmental Sciences and Sydney Medical School, The University of Sydney, Sydney, New South Wales 2006, Australia.
authors: Jemma L
authors: JL
authors: Geoghegan
authors: School of Mathematics and Statistics and Charles Perkins Centre, The University of Sydney, Sydney, New South Wales 2006, Australia.
authors: Alistair M
authors: AM
authors: Senior
authors: Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Life and Environmental Sciences and Sydney Medical School, The University of Sydney, Sydney, New South Wales 2006, Australia edward.holmes@sydney.edu.au.
authors: Edward C
authors: 0000-0001-9596-3552
authors: EC
authors: Holmes
mesh_terms: D005075:Biological Evolution; D004463:Ecology; D005828:Genetics, Population; D054884:Host-Pathogen Interactions / Q000235:genetics*; D008954:Models, Biological; D009154:Mutation; D014780:Viruses / Q000235:genetics* / Q000472:pathogenicity
keywords: adaptation; emerging diseases; evolution; influenza; spillover; virus