Rapid Intrahost Evolution of Human Cytomegalovirus Is Shaped by Demography and Positive Selection
Figure 3
HCMV populations are highly differentiated across compartments.
High throughput sequence data was generated on HCMV populations collected from 5 infants from either the urine or plasma compartment or both compartments (patient B103). Panel A: Consensus sequences were generated from the population data of each sample and maximum likelihood phylogenetic trees were constructed from whole genome alignments. Sequences longitudinally sampled from the same compartment of the same host clustered together. In contrast, B103 sequences sampled from the urine and plasma at the same time were highly differentiated and clustered more closely with sequences from other hosts. Intriguingly, plasma sequences from two hosts appeared (M103 and B103) to form a single clade, a result consistent with convergent evolution acting on plasma populations. Node labels represent bootstrap values from 100 replicates and the tree was rooted with the HCMV reference sequence (Strain Merlin, Ref Seq ID: NC_006273). Panel B: Population differentiation between the populations was measured by estimating the summary statistic FST for the specimen pairings. Higher values of FST indicate higher levels of population differentiation. HCMV populations are relatively stable across time when measuring populations collected from the same compartment of a single host or between monozygotic, monochorionic twins (MS1 and MS2). B103 populations sampled from different compartments at a single timepoint showed elevated FST values, indicative of higher levels of population differentiation. The level of differentiation observed between compartments in a single patient is comparable to that observed between populations collected from unrelated patients. Error bars represent 95% confidence intervals. ANOVA analysis: P = 6.7×10−13.