A model for within- and between-host evolution in pathogens
- 1University of North Carolina at Chapel Hill
Abstract
Many pathogenic and microbial species undergo complex life cycles wherein they experience drastic bottlenecks during invasion into a host and rapid growth within hosts. The effects of such a complex population history on patterns of genetic variation is not currently understood. We model a pathogen population as a metapopulation where each deme represents a host and incorporate transmission dynamics as well as the effects of transmission bottlenecks. We employ a coalescent framework, obtaining analytical expressions for pairwise times to coalescence and genetic differentiation within and between hosts. We find that recurrent bottlenecks rescale the coalescent process within hosts to the size of the bottleneck, reducing within-host variation. In addition, the pairwise distribution of time to coalescence under our model deviates substantially from the Wright-Fisher process when the number of hosts (d) is of similar order to the size of the bottleneck (k), i.e., k [~] d and when m <<1/(2k) +1/(2d), where m is the migration rate. Otherwise, the pairwise process under our model converges in distribution to the Wright-Fisher process. Coalescent simulations show that under the same conditions the site frequency spectrum (SFS) under our model deviates from that under the Kingman coalescent and is drastically skewed towards singletons. Our results suggest that the inference of selection or demographic history from pathogen population genetics data may be systematically biased by the mechanics of pathogen reproduction, indicating a need for further theoretical work that can inform inference.
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BibTeX
@misc{crescenzi2026model,
title = {{A model for within- and between-host evolution in pathogens}},
author = {J. Crescenzi and A. McAvoy and P. Johri},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.24.754225},
url = {https://www.biorxiv.org/content/10.64898/2026.09.24.754225v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - A model for within- and between-host evolution in pathogens
AU - J. Crescenzi
AU - A. McAvoy
AU - P. Johri
PY - 2026
DA - 2026/09/24
PB - bioRxiv
DO - 10.64898/2026.09.24.754225
UR - https://www.biorxiv.org/content/10.64898/2026.09.24.754225v1
AB - Many pathogenic and microbial species undergo complex life cycles wherein they experience drastic bottlenecks during invasion into a host and rapid growth within hosts. The effects of such a complex population history on patterns of genetic variation is not currently understood. We model a pathogen population as a metapopulation where each deme represents a host and incorporate transmission dynamics as well as the effects of transmission bottlenecks. We employ a coalescent framework, obtaining analytical expressions for pairwise times to coalescence and genetic differentiation within and between hosts. We find that recurrent bottlenecks rescale the coalescent process within hosts to the size of the bottleneck, reducing within-host variation. In addition, the pairwise distribution of time to coalescence under our model deviates substantially from the Wright-Fisher process when the number of hosts (d) is of similar order to the size of the bottleneck (k), i.e., k [~] d and when m <<1/(2k) +1/(2d), where m is the migration rate. Otherwise, the pairwise process under our model converges in distribution to the Wright-Fisher process. Coalescent simulations show that under the same conditions the site frequency spectrum (SFS) under our model deviates from that under the Kingman coalescent and is drastically skewed towards singletons. Our results suggest that the inference of selection or demographic history from pathogen population genetics data may be systematically biased by the mechanics of pathogen reproduction, indicating a need for further theoretical work that can inform inference.
ER -