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This paper aims to simplify the problem by introducing the concept of a genomic transmission graph with three basic parameters: the effective number of hosts, the quantum of transmission and the crossing rate of transmission chains. This enables rapid simulation of coalescence times in a recombining parasite population with superinfection and cotransmission, and it also provides a mathematical framework for analysis of within-host variation. Taking malaria as an example, we use this theoretical model to examine how transmission dynamics and migration affect parasite genomic diversity, including the effective recombination rate and haplotypic metrics of recent common ancestry. We show how key transmission parameters can be inferred from deep sequencing data and as a proof of concept we estimate the Plasmodium falciparum transmission bottleneck. Finally we discuss the potential applications of this novel inferential framework in genomic surveillance for malaria control and elimination. 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Biol."},{"key":"ref-43","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.40845","article-title":"The origins and relatedness structure of mixed infections vary with local prevalence of P.Falciparum malaria.","volume":"8","author":"S Zhu","year":"2019","journal-title":"eLife."},{"key":"ref-44","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01270-4","article-title":"Examining the human infectious reservoir for Plasmodium falciparum malaria in areas of differing transmission intensity.","volume":"8","author":"B Gon\u00e7alves","year":"2017","journal-title":"Nat Commun."},{"key":"ref-45","doi-asserted-by":"publisher","first-page":"17758-17764","DOI":"10.1073\/pnas.1212380109","article-title":"The great human expansion.","volume":"109","author":"B Henn","year":"2012","journal-title":"Proc Natl Acad Sci U S A."},{"key":"ref-46","doi-asserted-by":"publisher","first-page":"3427-3439","DOI":"10.1093\/molbev\/mss161","article-title":"Genomic sequencing of Plasmodium falciparum 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Chang","year":"2015","journal-title":"Parasitology."},{"key":"ref-50","doi-asserted-by":"publisher","first-page":"e281-e289","DOI":"10.1016\/S1473-3099(20)30939-7","article-title":"Genomic-informed pathogen surveillance in Africa: opportunities and challenges.","volume":"21","author":"S Inzaule","year":"2021","journal-title":"Lancet Infect Dis."},{"key":"ref-51","doi-asserted-by":"publisher","first-page":"337-345","DOI":"10.1016\/S1473-3099(18)30068-9","article-title":"Origins of the current outbreak of multidrug-resistant malaria in Southeast Asia: a retrospective genetic study.","volume":"18","author":"R Amato","year":"2018","journal-title":"Lancet Infect Dis."},{"key":"ref-52","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-11-419","article-title":"Malaria parasite diversity and transmission intensity affect development of parasitological immunity in a mathematical model.","volume":"11","author":"P Eckhoff","year":"2012","journal-title":"Malar 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