Disease surveillance in recombining pathogens: multilocus genotypes identify sources of human Coccidioides infections

Abstract

Molecular surveillance of pathogenic microbes works by genotyping isolates with DNA fingerprinting techniques and then using these genotypes to assign individuals to populations. Clonality is assumed in many fingerprinting studies, although this assumption has been shown to be false for many organisms. To accommodate recombining organisms into surveillance programs, methods using population allele frequencies in combination with individual multilocus genotypes are necessary. Here, we develop a statistical method appropriate for haploid recombining microbes that allows individuals to be assigned to populations. We illustrate the usefulness of this technique by inferring the source populations for Coccidioides isolates recovered from patients treated outside the endemic area of Coccidioides sp., the etiological agents of human coccidioidomycosis, but with a travel history including visits to one or more endemic areas.

Figure 1

(A) The percentage of individuals correctly assigned to their source population as a function of F_st for loci with high allelic diversity (an average of 10 alleles locus⁻¹, thick lines) and low allelic diversity (an average of 4 alleles locus⁻¹, thin lines). The numbers of loci used in the BATs are shown for 20 (diamonds), 10 (triangles), and 5 loci (squares). Curves are approximated by using logistic regression (P < 0.001 for all curves). (B) Mean posterior probabilities for assignment to their original source population for 50 randomly selected isolates. Reference sample populations of size 5, 15, 30, and 45 are used, drawn from a simulated population of n = 5,000. F_st ≈ 0.16 between populations and assignments are shown for samples of 20, 10, and 5 loci (see A for the definitions of symbols).

Figure 2

Mean posterior probabilities for assignment to their original source population for isolates selected from simulated populations with varying recombination rates. Reference sample populations of 30 isolates and 20 loci are used with F_st set to ≈0.2. Posterior probabilities (line marked with ×) and their associated SDs (line marked with +) are marked, as well as a curve plotting the increase of the standardized I_A across the simulations.