Modeling the genetic relatedness of Plasmodium falciparum parasites following meiotic recombination and cotransmission

Unlike in most pathogens, multiple-strain (polygenomic) infections of P. falciparum are frequently composed of genetic siblings. These genetic siblings are the result of sexual reproduction and can coinfect the same host when cotransmitted by the same mosquito. The degree with which coinfecting strains are related varies among infections and populations. Because sexual recombination occurs within the mosquito, the relatedness of cotransmitted strains could depend on transmission dynamics, but little is actually known of the factors that influence the relatedness of cotransmitted strains. Part of the uncertainty stems from an incomplete understanding of how within-host and within-vector dynamics affect cotransmission. Cotransmission is difficult to examine experimentally but can be explored using a computational model. We developed a malaria transmission model that simulates sexual reproduction in order to understand what determines the relatedness of cotransmitted strains. This study highlights how the relatedness of cotransmitted strains depends on both within-host and within-vector dynamics including the complexity of infection. We also used our transmission model to analyze the genetic relatedness of polygenomic infections following a series of multiple transmission events and examined the effects of superinfection. Understanding the factors that influence the relatedness of cotransmitted strains could lead to a better understanding of the population-genetic correlates of transmission and therefore be important for public health.Author summary: Genomic studies of P. falciparum reveal that multi-strain infections can include genetically related strains. P. falciparum must reproduce sexually in the mosquito vector. One consequence of sexual reproduction is that parasites cotransmitted by the same mosquito are related to one another. The degree of genetic relatedness of these parasites can be as great as that of full-siblings. However, our understanding of the cotransmission process is incomplete, and little is known of the role of cotransmission in influencing population genomic processes. To help bridge this gap, we developed a simulation model to determine which of the steps involved in transmission have the greatest impact on the relatedness of parasites cotransmitted by a mosquito vector. The primary goal of this study is to characterize the outcomes of cotransmission following single or multiple transmission events. Our model yields new insights into the cotransmission process, which we believe will be useful for understanding the results from more complicated population models and epidemiological conditions. Such an understanding is important for the use of population genomics to inform public health decisions as well as for understanding of parasite evolution.