Phylodynamics of rapidly adapting pathogens: extinction and speciation of a Red Queen

Rapidly evolving pathogens like influenza viruses can persist by accumulating antigenic novelty fast enough to evade the adaptive immunity of the host population, yet without continuous accumulation of genetic diversity. This dynamical state is often compared to the Red Queen evolving as fast as it can just to maintain its foothold in the host population: Accumulation of antigenic novelty is balanced by the build-up of host immunity. Such Red Queen States (RQS) of continuous adaptation in large rapidly mutating populations are well understood in terms of Traveling Wave (TW) theories of population genetics. Here we shall make explicit the mapping of the established Multi-strain Susceptible-Infected-Recovered (SIR) model onto the TW theory and demonstrate that a pathogen can persist in RQS if cross-immunity is long-ranged and its population size is large populations allowing for rapid adaptation. We then investigate the stability of this state focusing on the rate of extinction and the rate of “speciation” defined as antigenic divergence of viral strains beyond the range of cross-inhibition. RQS states are transient, but in a certain range of evolutionary parameters can exist for the time long compared to the typical time to the most recent common ancestor (TMRCA). In this range the steady TW is unstable and the antigenic advance of the lead strains relative to the typical co-circulating viruses tends to oscillate. This results in large fluctuations in prevalence that facilitate extinction. We shall demonstrate that the rate of TW fission into antigenically uncoupled viral populations is related to fluctuations of TMRCA and construct a “phase diagram” identifying different regimes of viral phylodynamics as a function of evolutionary parameters.

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Phylodynamic theory of persistence, extinction and speciation of rapidly adapting pathogens

eLife ◽

10.7554/elife.44205 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 5

Author(s):

Le Yan ◽

Richard A Neher ◽

Boris I Shraiman

Keyword(s):

Common Ancestor ◽

Large Population ◽

Wave Model ◽

Influenza Viruses ◽

Recent Common Ancestor ◽

Most Recent Common Ancestor ◽

Antigenic Properties ◽

Population Sizes ◽

Cross Immunity ◽

Cross Inhibition

Rapidly evolving pathogens like influenza viruses can persist by changing their antigenic properties fast enough to evade the adaptive immunity, yet they rarely split into diverging lineages. By mapping the multi-strain Susceptible-Infected-Recovered model onto the traveling wave model of adapting populations, we demonstrate that persistence of a rapidly evolving, Red-Queen-like state of the pathogen population requires long-ranged cross-immunity and sufficiently large population sizes. This state is unstable and the population goes extinct or ‘speciates’ into two pathogen strains with antigenic divergence beyond the range of cross-inhibition. However, in a certain range of evolutionary parameters, a single cross-inhibiting population can exist for times long compared to the time to the most recent common ancestor (TM⁢R⁢C⁢A) and gives rise to phylogenetic patterns typical of influenza virus. We demonstrate that the rate of speciation is related to fluctuations of TM⁢R⁢C⁢A and construct a ‘phase diagram’ identifying different phylodynamic regimes as a function of evolutionary parameters.

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Genetic variability under the seedbank coalescent

10.1101/017244 ◽

2015 ◽

Author(s):

Jochen Blath ◽

Bjarki Eldon ◽

Adrian Casanova ◽

Noemi Kurt ◽

Maite Wilke-Berenguer

Keyword(s):

Genetic Variability ◽

Frequency Spectrum ◽

Common Ancestor ◽

Scaling Limit ◽

Natural Populations ◽

Recent Common Ancestor ◽

Most Recent Common Ancestor ◽

Active Population ◽

Large Populations ◽

Site Frequency Spectrum

We analyse patterns of genetic variability of populations in the presence of a large seedbank with the help of a new coalescent structure called the seedbank coalescent. This ancestral process appears naturally as scaling limit of the genealogy of large populations that sustain seedbanks, if the seedbank size and individual dormancy times are of the same order as the active population. Mutations appear as Poisson processes on the active lineages, and potentially at reduced rate also on the dormant lineages. The presence of `dormant' lineages leads to qualitatively altered times to the most recent common ancestor and non-classical patterns of genetic diversity. To illustrate this we provide a Wright-Fisher model with seedbank component and mutation, motivated from recent models of microbial dormancy, whose genealogy can be described by the seedbank coalescent. Based on our coalescent model, we derive recursions for the expectation and variance of the time to most recent common ancestor, number of segregating sites, pairwise differences, and singletons. Estimates (obtained by simulations) of the distributions of commonly employed distance statistics, in the presence and absence of a seedbank, are compared. The effect of a seedbank on the expected site-frequency spectrum is also investigated using simulations. Our results indicate that the presence of a large seedbank considerably alters the distribution of some distance statistics, as well as the site-frequency spectrum. Thus, one should be able to detect from genetic data the presence of a large seedbank in natural populations.

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On the Use of Star-Shaped Genealogies in Inference of Coalescence Times

Genetics ◽

10.1093/genetics/164.4.1677 ◽

2003 ◽

Vol 164 (4) ◽

pp. 1677-1682 ◽

Cited By ~ 1

Author(s):

Noah A Rosenberg ◽

Aaron E Hirsh

Keyword(s):

Growth Rate ◽

Population Size ◽

Exponential Growth ◽

Common Ancestor ◽

Pairwise Comparison ◽

Recent Common Ancestor ◽

Most Recent Common Ancestor ◽

Large Populations ◽

Tree Length ◽

Coalescence Times

AbstractGenealogies from rapidly growing populations have approximate “star” shapes. We study the degree to which this approximation holds in the context of estimating the time to the most recent common ancestor (TMRCA) of a set of lineages. In an exponential growth scenario, we find that unless the product of population size (N) and growth rate (r) is at least ∼105, the “pairwise comparison estimator” of TMRCA that derives from the star genealogy assumption has bias of 10-50%. Thus, the estimator is appropriate only for large populations that have grown very rapidly. The “tree-length estimator” of TMRCA is more biased than the pairwise comparison estimator, having low bias only for extremely large values of Nr.

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Allelic Genealogies in Sporophytic Self-Incompatibility Systems in Plants

Genetics ◽

10.1093/genetics/150.3.1187 ◽

1998 ◽

Vol 150 (3) ◽

pp. 1187-1198 ◽

Cited By ~ 9

Author(s):

Mikkel H Schierup ◽

Xavier Vekemans ◽

Freddy B Christiansen

Keyword(s):

Dominance Hierarchy ◽

Common Ancestor ◽

Recent Common Ancestor ◽

Self Incompatibility ◽

Most Recent Common Ancestor ◽

Dominance Interactions ◽

Turnover Process ◽

Neutral Gene ◽

Interspecific Comparisons ◽

Coalescence Times

Abstract Expectations for the time scale and structure of allelic genealogies in finite populations are formed under three models of sporophytic self-incompatibility. The models differ in the dominance interactions among the alleles that determine the self-incompatibility phenotype: In the SSIcod model, alleles act codominantly in both pollen and style, in the SSIdom model, alleles form a dominance hierarchy, and in SSIdomcod, alleles are codominant in the style and show a dominance hierarchy in the pollen. Coalescence times of alleles rarely differ more than threefold from those under gametophytic self-incompatibility, and transspecific polymorphism is therefore expected to be equally common. The previously reported directional turnover process of alleles in the SSIdomcod model results in coalescence times lower and substitution rates higher than those in the other models. The SSIdom model assumes strong asymmetries in allelic action, and the most recessive extant allele is likely to be the most recent common ancestor. Despite these asymmetries, the expected shape of the allele genealogies does not deviate markedly from the shape of a neutral gene genealogy. The application of the results to sequence surveys of alleles, including interspecific comparisons, is discussed.

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Molecular epidemiological characteristics of echovirus 6 in mainland China: extensive circulation of genotype F from 2007 to 2018

Archives of Virology ◽

10.1007/s00705-020-04934-7 ◽

2021 ◽

Author(s):

Wenjun Cheng ◽

Tianjiao Ji ◽

Shuaifeng Zhou ◽

Yong Shi ◽

Lili Jiang ◽

...

Keyword(s):

Common Ancestor ◽

Mainland China ◽

Recent Common Ancestor ◽

Genetic Characteristics ◽

Most Recent Common Ancestor ◽

Significant Difference ◽

Echovirus 6 ◽

Epidemiological Characteristics ◽

Highest Posterior Density ◽

Genotype F

AbstractEchovirus 6 (E6) is associated with various clinical diseases and is frequently detected in environmental sewage. Despite its high prevalence in humans and the environment, little is known about its molecular phylogeography in mainland China. In this study, 114 of 21,539 (0.53%) clinical specimens from hand, foot, and mouth disease (HFMD) cases collected between 2007 and 2018 were positive for E6. The complete VP1 sequences of 87 representative E6 strains, including 24 strains from this study, were used to investigate the evolutionary genetic characteristics and geographical spread of E6 strains. Phylogenetic analysis based on VP1 nucleotide sequence divergence showed that, globally, E6 strains can be grouped into six genotypes, designated A to F. Chinese E6 strains collected between 1988 and 2018 were found to belong to genotypes C, E, and F, with genotype F being predominant from 2007 to 2018. There was no significant difference in the geographical distribution of each genotype. The evolutionary rate of E6 was estimated to be 3.631 × 10-3 substitutions site-1 year-1 (95% highest posterior density [HPD]: 3.2406 × 10-3-4.031 × 10-3 substitutions site-1 year-1) by Bayesian MCMC analysis. The most recent common ancestor of the E6 genotypes was traced back to 1863, whereas their common ancestor in China was traced back to around 1962. A small genetic shift was detected in the Chinese E6 population size in 2009 according to Bayesian skyline analysis, which indicated that there might have been an epidemic around that year.

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Molecular epidemiology of coxsackievirus A16 circulating in children in Beijing, China from 2010 to 2019

World Journal of Pediatrics ◽

10.1007/s12519-021-00451-y ◽

2021 ◽

Author(s):

Ya-Fang Hu ◽

Li-Ping Jia ◽

Fang-Yuan Yu ◽

Li-Ying Liu ◽

Qin-Wei Song ◽

...

Keyword(s):

Molecular Epidemiology ◽

Evolutionary Rate ◽

Foot And Mouth Disease ◽

Recent Common Ancestor ◽

Rt Pcr ◽

Coxsackievirus A16 ◽

Most Recent Common Ancestor ◽

Etiological Agents ◽

High Level ◽

And Control

Abstract Background Coxsackievirus A16 (CVA16) is one of the major etiological agents of hand, foot and mouth disease (HFMD). This study aimed to investigate the molecular epidemiology and evolutionary characteristics of CVA16. Methods Throat swabs were collected from children with HFMD and suspected HFMD during 2010–2019. Enteroviruses (EVs) were detected and typed by real-time reverse transcription-polymerase chain reaction (RT-PCR) and RT-PCR. The genotype, evolutionary rate, the most recent common ancestor, population dynamics and selection pressure of CVA16 were analyzed based on viral protein gene (VP1) by bioinformatics software. Results A total of 4709 throat swabs were screened. EVs were detected in 3180 samples and 814 were CVA16 positive. More than 81% of CVA16-positive children were under 5 years old. The prevalence of CVA16 showed obvious periodic fluctuations with a high level during 2010–2012 followed by an apparent decline during 2013–2017. However, the activities of CVA16 increased gradually during 2018–2019. All the Beijing CVA16 strains belonged to sub-genotype B1, and B1b was the dominant strain. One B1c strain was detected in Beijing for the first time in 2016. The estimated mean evolutionary rate of VP1 gene was 4.49 × 10–3 substitution/site/year. Methionine gradually fixed at site-23 of VP1 since 2012. Two sites were detected under episodic positive selection, one of which (site-223) located in neutralizing linear epitope PEP71. Conclusions The dominant strains of CVA16 belonged to clade B1b and evolved in a fast evolutionary rate during 2010–2019 in Beijing. To provide more favorable data for HFMD prevention and control, it is necessary to keep attention on molecular epidemiological and evolutionary characteristics of CVA16.

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The Ancestry of a Sample of Sequences Subject to Recombination

Genetics ◽

10.1093/genetics/151.3.1217 ◽

1999 ◽

Vol 151 (3) ◽

pp. 1217-1228 ◽

Cited By ~ 1

Author(s):

Carsten Wiuf ◽

Jotun Hein

Keyword(s):

Genetic Distance ◽

Population Size ◽

Upper Bound ◽

Recombination Rate ◽

Common Ancestor ◽

Recent Common Ancestor ◽

Sequence Length ◽

Most Recent Common Ancestor ◽

The Mean ◽

Mean Time

Abstract In this article we discuss the ancestry of sequences sampled from the coalescent with recombination with constant population size 2N. We have studied a number of variables based on simulations of sample histories, and some analytical results are derived. Consider the leftmost nucleotide in the sequences. We show that the number of nucleotides sharing a most recent common ancestor (MRCA) with the leftmost nucleotide is ≈log(1 + 4N Lr)/4Nr when two sequences are compared, where L denotes sequence length in nucleotides, and r the recombination rate between any two neighboring nucleotides per generation. For larger samples, the number of nucleotides sharing MRCA with the leftmost nucleotide decreases and becomes almost independent of 4N Lr. Further, we show that a segment of the sequences sharing a MRCA consists in mean of 3/8Nr nucleotides, when two sequences are compared, and that this decreases toward 1/4Nr nucleotides when the whole population is sampled. A measure of the correlation between the genealogies of two nucleotides on two sequences is introduced. We show analytically that even when the nucleotides are separated by a large genetic distance, but share MRCA, the genealogies will show only little correlation. This is surprising, because the time until the two nucleotides shared MRCA is reciprocal to the genetic distance. Using simulations, the mean time until all positions in the sample have found a MRCA increases logarithmically with increasing sequence length and is considerably lower than a theoretically predicted upper bound. On the basis of simulations, it turns out that important properties of the coalescent with recombinations of the whole population are reflected in the properties of a sample of low size.

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Genome Sequence Analysis of First Ross River Virus Isolate from Papua New Guinea Indicates Long-Term, Local Evolution

Viruses ◽

10.3390/v13030482 ◽

2021 ◽

Vol 13 (3) ◽

pp. 482

Author(s):

Alice Michie ◽

John S. Mackenzie ◽

David W. Smith ◽

Allison Imrie

Keyword(s):

Papua New Guinea ◽

Large Scale ◽

Solomon Islands ◽

Febrile Illness ◽

New Guinea ◽

Recent Common Ancestor ◽

Ross River Virus ◽

Most Recent Common Ancestor ◽

Mean Time

Ross River virus (RRV) is the most medically significant mosquito-borne virus of Australia, in terms of human morbidity. RRV cases, characterised by febrile illness and potentially persistent arthralgia, have been reported from all Australian states and territories. RRV was the cause of a large-scale epidemic of multiple Pacific Island countries and territories (PICTs) from 1979 to 1980, involving at least 50,000 cases. Historical evidence of RRV seropositivity beyond Australia, in populations of Papua New Guinea (PNG), Indonesia and the Solomon Islands, has been documented. We describe the genomic characterisation and timescale analysis of the first isolate of RRV to be sampled from PNG to date. Our analysis indicates that RRV has evolved locally within PNG, independent of Australian lineages, over an approximate 40 year period. The mean time to most recent common ancestor (tMRCA) of the unique PNG clade coincides with the initiation of the PICTs epidemic in mid-1979. This may indicate that an ancestral variant of the PNG clade was seeded into the region during the epidemic, a period of high RRV transmission. Further epidemiological and molecular-based surveillance is required in PNG to better understand the molecular epidemiology of RRV in the general Australasian region.

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Modeling and simulation of the spread of H1N1 flu with periodic vaccination

International Journal of Biomathematics ◽

10.1142/s1793524516500030 ◽

2015 ◽

Vol 09 (01) ◽

pp. 1650003 ◽

Cited By ~ 1

Author(s):

Islam A. Moneim

Keyword(s):

Influenza A ◽

Vaccination Strategy ◽

Vaccination Rate ◽

Influenza Viruses ◽

Sirs Epidemic Model ◽

Sirs Model ◽

Influenza A H1n1 ◽

Large Populations ◽

Stability Results ◽

Influenza H1n1

Influenza H1N1 has been found to exhibit oscillatory levels of incidence in large populations. Clear peaks for influenza H1N1 are observed in several countries including Vietnam each year [M. F. Boni, B. H. Manh, P. Q. Thai, J. Farrar, T. Hien, N. T. Hien, N. Van Kinh and P. Horby, Modelling the progression of pandemic influenza A (H1N1) in Vietnam and the opportunities for reassortment with other influenza viruses, BMC Med. 7 (2009) 43, Doi: 10.1186/1741-7015-7-43]. So it is important to study seasonal forces and factors which can affect the transmission of this disease. This paper studies an SIRS epidemic model with seasonal vaccination rate. This SIRS model has a unique disease-free solution (DFS). The value R0, the basic reproduction number is obtained when the vaccination is a periodic function. Stability results for the DFS are obtained when R0 < 1. The disease persists in the population and remains endemic if R0 > 1. Also when R0 > 1 existence of a nonzero periodic solution is proved. These results obtained for our model when the vaccination strategy is a non-constant time-dependent function.

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Testing the spatial and temporal framework of speciation in an ancient lake species flock: the leech genus <i>Dina</i> (Hirudinea: Erpobdellidae) in Lake Ohrid

Biogeosciences ◽

10.5194/bg-7-3387-2010 ◽

2010 ◽

Vol 7 (11) ◽

pp. 3387-3402 ◽

Cited By ~ 32

Author(s):

S. Trajanovski ◽

C. Albrecht ◽

K. Schreiber ◽

R. Schultheiß ◽

T. Stadler ◽

...

Keyword(s):

Molecular Clock ◽

Abiotic Factors ◽

Time Frame ◽

Recent Common Ancestor ◽

Species Flock ◽

Ancient Lake ◽

Lake Ohrid ◽

Most Recent Common Ancestor ◽

Extant Species

Abstract. Ancient Lake Ohrid on the Balkan Peninsula is considered to be the oldest ancient lake in Europe with a suggested Plio-/Pleistocene age. Its exact geological age, however, remains unknown. Therefore, molecular clock data of Lake Ohrid biota may serve as an independent constraint of available geological data, and may thus help to refine age estimates. Such evolutionary data may also help unravel potential biotic and abiotic factors that promote speciation events. Here, mitochondrial sequencing data of one of the largest groups of endemic taxa in the Ohrid watershed, the leech genus Dina, is used to test whether it represents an ancient lake species flock, to study the role of potential horizontal and vertical barriers in the watershed for evolutionary events, to estimate the onset of diversification in this group based on molecular clock analyses, and to compare this data with data from other endemic species for providing an approximate time frame for the origin of Lake Ohrid. Based on the criteria speciosity, monophyly and endemicity, it can be concluded that Dina spp. from the Ohrid watershed, indeed, represents an ancient lake species flock. Lineage sorting of its species, however, does not seem to be complete and/or hybridization may occur. Analyses of population structures of Dina spp. in the Ohrid watershed indicate a horizontal zonation of haplotypes from spring and lake populations, corroborating the role of lake-side springs, particularly the southern feeder springs, for evolutionary processes in endemic Ohrid taxa. Vertical differentiation of lake taxa, however, appears to be limited, though differences between populations from the littoral and the profundal are apparent. Molecular clock analyses indicate that the most recent common ancestor of extant species of this flock is approximately 1.99 ± 0.83 million years (Ma) old, whereas the split of the Ohrid Dina flock from a potential sister taxon outside the lake is estimated at 8.30 ± 3.60 Ma. Comparisons with other groups of endemic Ohrid species indicated that in all cases, diversification within the watershed started ≤2 Ma ago. Thus, this estimate may provide information on a minimum age for the origin of Lake Ohrid. Maximum ages are less consistent and generally less reliable. But cautiously, a maximum age of 3 Ma is suggested. Interestingly, this time frame of approximately 2–3 Ma ago for the origin of Lake Ohrid, generated based on genetic data, well fits the time frame most often used in the literature by geologists.

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