Transmission of SARS-CoV-2 in domestic cats imposes a narrow bottleneck

AbstractThe evolutionary mechanisms by which SARS-CoV-2 viruses adapt to mammalian hosts and, potentially, undergo antigenic evolution depend on the ways genetic variation is generated and selected within and between individual hosts. Using domestic cats as a model, we show that SARS-CoV-2 consensus sequences remain largely unchanged over time within hosts, while dynamic sub-consensus diversity reveals processes of genetic drift and weak purifying selection. We further identify a notable variant at amino acid position 655 in Spike (H655Y), which was previously shown to confer escape from human monoclonal antibodies. This variant arises rapidly and persists at intermediate frequencies in index cats. It also becomes fixed following transmission in two of three pairs. These dynamics suggest this site may be under positive selection in this system and illustrate how a variant can quickly arise and become fixed in parallel across multiple transmission pairs. Transmission of SARS-CoV-2 in cats involved a narrow bottleneck, with new infections founded by fewer than ten viruses. In RNA virus evolution, stochastic processes like narrow transmission bottlenecks and genetic drift typically act to constrain the overall pace of adaptive evolution. Our data suggest that here, positive selection in index cats followed by a narrow transmission bottleneck may have instead accelerated the fixation of S H655Y, a potentially beneficial SARS-CoV-2 variant. Overall, our study suggests species- and context-specific adaptations are likely to continue to emerge. This underscores the importance of continued genomic surveillance for new SARS-CoV-2 variants as well as heightened scrutiny for signatures of SARS-CoV-2 positive selection in humans and mammalian model systems.Author summaryThrough ongoing human adaptation, spill-back events from other animal intermediates, or with the distribution of vaccines and therapeutics, the landscape of SARS-CoV-2 genetic variation is certain to change. The evolutionary mechanisms by which SARS-CoV-2 will continue to adapt to mammalian hosts depend on genetic variation generated within and between hosts. Here, using domestic cats as a model, we show that within-host SARS-CoV-2 genetic variation is predominantly influenced by genetic drift and purifying selection. Transmission of SARS-CoV-2 between hosts is defined by a narrow transmission bottleneck, involving 2-5 viruses. We further identify a notable variant at amino acid position 655 in Spike (H655Y), which arises rapidly and is transmitted in cats. Spike H655Y has been previously shown to confer escape from human monoclonal antibodies and is currently found in over 1000 human sequences. Overall, our study suggests species- and context-specific adaptations are likely to continue to emerge, underscoring the importance of continued genomic surveillance in humans and non-human mammalian hosts.

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Transmission of SARS-CoV-2 in domestic cats imposes a narrow bottleneck

PLoS Pathogens ◽

10.1371/journal.ppat.1009373 ◽

2021 ◽

Vol 17 (2) ◽

pp. e1009373

Author(s):

Katarina M. Braun ◽

Gage K. Moreno ◽

Peter J. Halfmann ◽

Emma B. Hodcroft ◽

David A. Baker ◽

...

Keyword(s):

Positive Selection ◽

Genetic Drift ◽

Rna Virus ◽

Purifying Selection ◽

Amino Acid Position ◽

Model Systems ◽

Domestic Cats ◽

Evolutionary Mechanisms ◽

Consensus Sequences ◽

Context Specific

The evolutionary mechanisms by which SARS-CoV-2 viruses adapt to mammalian hosts and, potentially, undergo antigenic evolution depend on the ways genetic variation is generated and selected within and between individual hosts. Using domestic cats as a model, we show that SARS-CoV-2 consensus sequences remain largely unchanged over time within hosts, while dynamic sub-consensus diversity reveals processes of genetic drift and weak purifying selection. We further identify a notable variant at amino acid position 655 in Spike (H655Y), which was previously shown to confer escape from human monoclonal antibodies. This variant arises rapidly and persists at intermediate frequencies in index cats. It also becomes fixed following transmission in two of three pairs. These dynamics suggest this site may be under positive selection in this system and illustrate how a variant can quickly arise and become fixed in parallel across multiple transmission pairs. Transmission of SARS-CoV-2 in cats involved a narrow bottleneck, with new infections founded by fewer than ten viruses. In RNA virus evolution, stochastic processes like narrow transmission bottlenecks and genetic drift typically act to constrain the overall pace of adaptive evolution. Our data suggest that here, positive selection in index cats followed by a narrow transmission bottleneck may have instead accelerated the fixation of S H655Y, a potentially beneficial SARS-CoV-2 variant. Overall, our study suggests species- and context-specific adaptations are likely to continue to emerge. This underscores the importance of continued genomic surveillance for new SARS-CoV-2 variants as well as heightened scrutiny for signatures of SARS-CoV-2 positive selection in humans and mammalian model systems.

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Global patterns of genetic variation and association with clinical phenotypes at genes involved in SARS-CoV-2 infection

10.1101/2021.06.28.21259529 ◽

2021 ◽

Author(s):

Chao Zhang ◽

Anurag Verma ◽

Yuanqing Feng ◽

Marcelo C. R. Melo ◽

Michael McQuillan ◽

...

Keyword(s):

Genetic Variation ◽

Positive Selection ◽

Low Frequency ◽

Purifying Selection ◽

Upper Respiratory Tract ◽

Genetic Associations ◽

Hunter Gatherers ◽

Clinical Phenotypes ◽

Global Patterns ◽

Coding Variants

The COVID-19 pandemic caused by SARS-COV-2 has had a devastating impact on population health. We investigated global patterns of genetic variation and signatures of natural selection at host genes relevant to SARS-CoV-2 infection (ACE2, TMPRSS2, DPP4, and LY6E). We analyzed novel data from 2,012 ethnically diverse Africans, 15,997 individuals of European (7,061) and African (8,916) ancestry recruited by the Penn Medicine BioBank (PMBB), and comparative data from 2,504 individuals from the 1000 Genomes project. At ACE2 we identified 41 non-synonymous variants, found to be at low frequency in most populations. However, three non-synonymous variants were frequent among Central African hunter-gatherers (CAHG) from Cameroon, and signatures of positive selection could be detected on haplotypes encompassing those variants. We also detected signatures of positive selection for variants at regulatory regions upstream of ACE2 in diverse African populations. At TMPRSS2, we identified 48 non-synonymous variants, several of which are common in global populations, and 13 amino acid changes that are fixed in the human lineage after divergence from Chimpanzee. At DPP4 and LY6E most variants were rare in global populations indicating that purifying selection is acting at these loci. At all four loci, we identified common non-coding variants associated with gene expression that vary in frequency across global populations. By analyzing electronic health records from the PMBB we discovered genetic associations with clinical phenotypes, such as respiratory failure with ACE2 and upper respiratory tract infection with DPP4. Our study provides new insights into global variation at genes potentially affecting susceptibility to SARS-CoV-2 infection.

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Somatic genetic drift and multi-level selection in modular species

10.1101/833335 ◽

2019 ◽

Cited By ~ 1

Author(s):

Lei Yu ◽

Christoffer Boström ◽

Sören Franzenburg ◽

Till Bayer ◽

Tal Dagan ◽

...

Keyword(s):

Genetic Variation ◽

Genetic Drift ◽

Purifying Selection ◽

Cellular Level ◽

Population Bottlenecks ◽

Multi Level ◽

Multiple Levels ◽

Level Of Selection ◽

Multicellular Organisms ◽

Clonal Species

AbstractCells in multicellular organisms are genetically heterogeneous owing to somatic mutations. The accumulation of somatic genetic variation in species undergoing asexual (or clonal) reproduction (termed modular species) may lead to phenotypic heterogeneity among modules. However, abundance and dynamics of somatic genetic variation under clonal growth, a widespread life history in nature, remain poorly understood. Here we show that branching events in a seagrass clone or genet leads to population bottlenecks at the cellular level and hence the evolution of genetically differentiated modules. Studying inter-module somatic genetic variation, we uncovered thousands of SNPs that segregated among modules. The strength of purifying selection on mosaic genetic variation was greater at the intra-module comparing with the inter-module level. Our study provides evidence for the operation of selection at multiple levels, of cell population and modules. Somatic genetic drift leads to the emergence of genetically unique modules; hence, modules in long-lived clonal species constitute an appropriate elementary level of selection and individuality.

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