Evolutionary history of <i>M. tuberculosis</i> strains isolated from a cluster of cases in New Zealand.

<p>Relationships were inferred by examining parsimony and nonparsimony informative single nucleotide polymorphisms (SNPs). <b>Panel A</b>: parallelogram of network analysis using 34 SNPs including five homoplastic SNPs. <b>Panel B</b>: Evolutionary tree using the same 34 SNPs as in A rooted on <i>M. tuberculosis</i> H₃₇Rv analyzed using Neighbor-joining method. Panel C. Evolutionary tree examining 29 nonparsimony SNPs using the Neighbor-joining method. The evolutionary distances represent the number of SNP differences per strain.</p

Epidemiological relationships among 11 New Zealand <i>M. tuberculosis</i> cases.

<p>Chronological representation of different subjects in a New Zealand TB outbreak. Each square represent a subject at the time of the TB diagnosis. Broken lines represent known close direct contact with the initial index case “X” during X's period of infectiousness. Solid lines show assumed connections between a case of presumed reactivation (C1 to C2) and a case of potential child-parent transmission (A to T).</p

Number of single nucleotide polymorphisms differences between each strain.

<p>Number of single nucleotide polymorphisms differences between each strain.</p

Mutation versus replication rates during the latency period.

<p>To evaluate if the mutation rate was different in early versus late period of latent-reactivated disease, we estimated the mutation rate (calculated as untis of mutation/bp/generation) for isolates with reactivation of TB for the latent and reactivated years. <b>Panel A</b>: A schematic representation for the evaluation of the rate of mutation in the latency period. The mutation rate of the recent activated TB (strains C1 and E) was subtracted from the late activated TB (strains O and S).<b>Panel B</b>: The mutation rate for the latent period was calculated using the difference between the number of mutations for the early reactivation phase and the late reactivated phase. The result was divided by the genome size multiplied by the number of generations for O and S combined in the presumed latent period. All these calculations implicitly assume a homogeneous mutation rate across the genome and over time and when combining activation groups, across isolates. Analyses were performed using PROC GENMOD in SAS 9.2 (SAS Institute Inc, Cary, NC). Graphics were generated using R 2.12.2 (R Foundation for Statistical Computing).</p

Single nucleotide polymorphisms identified in sequenced isolates.

1<p>reference genome.</p

In vivo mutation rates in <i>M. tuberculosis</i> strains for generation times ranging from 18 to 240 hours.

<p>The mutation rate for each of the <i>M. tuberculosis</i> isolates was estimated using equation (1) in Ford <i>et al</i>, and calculated as untis of mutation/bp/generation <b>Panel A</b>: The mutation rate for each <i>M. tuberculosis</i> isolate in the study. Isolate C1 and E are from recent infection while strains O and S from reactivation after a prolonged period of latency. The yellow areas represent 95% confidence intervals. <b>Panel B</b>: Isolates with recent infection (E and C1) and reactivation after prolonged latency (O and S) were combined to obtain overall estimates of mutation rates of recent and latent-reactivated disease. The yellow areas represent 95% confidence intervals.</p