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. 2023 Jan 17;14(1):272.
doi: 10.1038/s41467-023-36001-5.

Rapid transmission and tight bottlenecks constrain the evolution of highly transmissible SARS-CoV-2 variants

Emily E Bendall  1 , Amy P Callear  2 , Amy Getz  2 , Kendra Goforth  2 , Drew Edwards  2 , Arnold S Monto  2 , Emily T Martin  2 , Adam S Lauring  3   4
Affiliations

Rapid transmission and tight bottlenecks constrain the evolution of highly transmissible SARS-CoV-2 variants

Emily E Bendall et al. Nat Commun. .

Abstract

Transmission bottlenecks limit the spread of novel mutations and reduce the efficiency of selection along a transmission chain. While increased force of infection, receptor binding, or immune evasion may influence bottleneck size, the relationship between transmissibility and the transmission bottleneck is unclear. Here we compare the transmission bottleneck of non-VOC SARS-CoV-2 lineages to those of Alpha, Delta, and Omicron. We sequenced viruses from 168 individuals in 65 households. Most virus populations had 0-1 single nucleotide variants (iSNV). From 64 transmission pairs with detectable iSNV, we identify a per clade bottleneck of 1 (95% CI 1-1) for Alpha, Delta, and Omicron and 2 (95% CI 2-2) for non-VOC. These tight bottlenecks reflect the low diversity at the time of transmission, which may be more pronounced in rapidly transmissible variants. Tight bottlenecks will limit the development of highly mutated VOC in transmission chains, adding to the evidence that selection over prolonged infections may drive their evolution.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Serial interval and timing of sample collection.
a Days between index symptom onset and household contact symptom onset for the indicated clades. “Non-VOC” includes all lineages not designated as a WHO variant of concern. No Beta variant transmission pairs were analyzed. b Days between symptom onset and collection of the sequenced specimen for the index case. Index cases from MHome are indicated in teal, and index cases from HIVE are indicated in red. Omicron had a shorter time between index symptom onset and sample collection for sequencing than non-VOC (ANOVA, df = 3, F = 8.138, p < 0.001) and Alpha. HIVE households had a shorter time than MHome households (ANOVA, df = 1, F = 15.363, p < 0.001). c RT-qPCR cycle threshold values (inverted y-axis) for all specimens collected from index cases. Sequenced specimens are indicated with filled circles.
Fig. 2
Fig. 2. Genetic diversity in sequenced specimens.
a Histogram of the number of iSNV per specimen. b iSNV frequency histogram.
Fig. 3
Fig. 3. Diversity across transmission pairs.
a The number of individuals per household with sequenced specimens. Colors represent the different clades. b Shared genetic diversity between transmission pairs. Each point is an iSNV within a transmission pair. Red points indicate mutation C29708T, which was shared in a single household (see text).
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