scholarly journals Prisoner of War dynamics explains the time-dependent pattern of substitution rates in viruses

2021 ◽  
Author(s):  
Mahan Ghafari ◽  
Peter Simmonds ◽  
Oliver G Pybus ◽  
Aris Katzourakis
Keyword(s):  
Power Law ◽  
Mechanistic Model ◽  
Evolutionary Rates ◽  
Time Dependent ◽  
Recent Common Ancestor ◽  
Evolutionary Mechanisms ◽  
Substitution Rates ◽  
Most Recent Common Ancestor ◽  
Wide Range ◽  
Rate Decay

AbstractMolecular clock dating is widely used to estimate timescales of phylogenetic histories and to infer rates at which species evolve. One of the major challenges with inferring rates of molecular evolution is the observation of a strong correlation between estimated rates and the timeframe of their measurements. Recent empirical analysis of virus evolutionary rates suggest that a power-law rate decay best explains the time-dependent pattern of substitution rates and that the same pattern is observed regardless of virus type (e.g. groups I-VII in the Baltimore classification). However there exists no explanation for this trend based on molecular evolutionary mechanisms. We provide a simple predictive mechanistic model of the time-dependent rate phenomenon, incorporating saturation and host constraints on the evolution of some sites. Our model recapitulates the ubiquitous power-law rate decay with a slope of −0.65 (95% HPD: −0.72, −0.52) and can satisfactorily account for the variation in inferred molecular evolutionary rates over a wide range of timeframes. We show that once the saturation of sites starts - typically after hundreds of years in RNA viruses and thousands of years in DNA viruses - standard substitution models fail to correctly estimate divergence times among species, while our model successfully re-creates the observed pattern of rate decay. We apply our model to re-date the diversification of genotypes of hepatitis C virus (HCV) to 396,000 (95% HPD: 326,000 - 425,000) years before present, a time preceding the dispersal of modern humans out of Africa, and also showed that the most recent common ancestor of sarbecoviruses dates back to 23,500 (95% HPD: 21,100 - 25,300) years ago, nearly thirty times older than previous estimates. This not only creates a radical new perspective for our understanding the origins of HCV but also suggests a substantial revision of evolutionary timescales of other viruses can be similarly achieved.

scholarly journals Genomic Analysis and Comparison of Two Gonorrhea Outbreaks

mBio ◽  
2016 ◽  
Vol 7 (3) ◽  
Author(s):  
Xavier Didelot ◽  
Janina Dordel ◽  
Lilith K. Whittles ◽  
Caitlin Collins ◽  
Nicole Bilek ◽  
...  
Keyword(s):  
United Kingdom ◽  
Genome Sequencing ◽  
Transmitted Disease ◽  
Control Measures ◽  
Health Concern ◽  
Single Type ◽  
Recent Common Ancestor ◽  
Data Sets ◽  
Most Recent Common Ancestor ◽  
Wide Range

ABSTRACT Gonorrhea is a sexually transmitted disease causing growing concern, with a substantial increase in reported incidence over the past few years in the United Kingdom and rising levels of resistance to a wide range of antibiotics. Understanding its epidemiology is therefore of major biomedical importance, not only on a population scale but also at the level of direct transmission. However, the molecular typing techniques traditionally used for gonorrhea infections do not provide sufficient resolution to investigate such fine-scale patterns. Here we sequenced the genomes of 237 isolates from two local collections of isolates from Sheffield and London, each of which was resolved into a single type using traditional methods. The two data sets were selected to have different epidemiological properties: the Sheffield data were collected over 6 years from a predominantly heterosexual population, whereas the London data were gathered within half a year and strongly associated with men who have sex with men. Based on contact tracing information between individuals in Sheffield, we found that transmission is associated with a median time to most recent common ancestor of 3.4 months, with an upper bound of 8 months, which we used as a criterion to identify likely transmission links in both data sets. In London, we found that transmission happened predominantly between individuals of similar age, sexual orientation, and location and also with the same HIV serostatus, which may reflect serosorting and associated risk behaviors. Comparison of the two data sets suggests that the London epidemic involved about ten times more cases than the Sheffield outbreak. IMPORTANCE The recent increases in gonorrhea incidence and antibiotic resistance are cause for public health concern. Successful intervention requires a better understanding of transmission patterns, which is not uncovered by traditional molecular epidemiology techniques. Here we studied two outbreaks that took place in Sheffield and London, United Kingdom. We show that whole-genome sequencing provides the resolution to investigate direct gonorrhea transmission between infected individuals. Combining genome sequencing with rich epidemiological information about infected individuals reveals the importance of several transmission routes and risk factors, which can be used to design better control measures.

scholarly journals Genomic and Micro-Evolutionary Features of Mammalian 2 orthobornavirus (Variegated Squirrel Bornavirus 1, VSBV-1)

2021 ◽  
Vol 9 (6) ◽  
pp. 1141
Author(s):  
Dániel Cadar ◽  
Jonas Schmidt-Chanasit ◽  
Dennis Tappe
Keyword(s):  
Evolutionary Dynamics ◽  
Animal Husbandry ◽  
Purifying Selection ◽  
Recent Common Ancestor ◽  
Positive Pressure ◽  
Evolutionary Mechanisms ◽  
Time Resolved ◽  
Viral Pathogen ◽  
Most Recent Common Ancestor ◽  
Evolutionary Features

Mammalian 2 orthobornavirus (VSBV-1) is an emerging zoonotic pathogen discovered in several exotic squirrel species and associated with fatal human encephalitis. The dynamics of VSBV-1 spread and evolution in its presumed natural hosts are unknown. Here, we present the phylogeny, micro-evolution, cross-species transmission and spread of VSBV-1 at a temporal and spatial resolution within the limits of animal husbandry. The results showed that VSBV-1 can be classified into six distinct groups and that the most recent common ancestor of the known German strains emerged at least 20 years ago. We here demonstrate that the genetic diversity of the VSBV-1 groups is shaped primarily by in situ evolution and most of the amino acid changes are deleterious polymorphisms removed by purifying selection. Evidence of adaptive evolution has been found in the G and L genes which might have an influence on transmission fitness. Furthermore, there was also evidence for some form of adaptive changes in the glycoprotein which suggests that many sites might be subjected to positive pressure evolving under episodic directional selection, indicating past occurrence of positive selection. Host switching events were detected as dominant evolutionary mechanisms driving the virus-host associations. Virus spread by animal trade followed by subsequent local micro-evolution in zoos and holdings is responsible for diversifying strains. Time-resolved phylogeny indicated that Prevost’s squirrels might be the original squirrel species carrying and seeding the virus in Germany. This study provides the first insight into the ecology and micro-evolutionary dynamics of this novel viral pathogen in the captive exotic squirrel population under artificial ecological conditions (zoos and animal husbandry) and co-housing of different squirrel species.

scholarly journals Frequentist Estimation of Coalescence Times From Nucleotide Sequence Data Using a Tree-Based Partition

Genetics ◽  
2002 ◽  
Vol 161 (1) ◽  
pp. 447-459 ◽  
Author(s):  
Hua Tang ◽  
David O Siegmund ◽  
Peidong Shen ◽  
Peter J Oefner ◽  
Marcus W Feldman
Keyword(s):  
Dna Sequences ◽  
Sequence Data ◽  
Recent Common Ancestor ◽  
Point Estimate ◽  
Nucleotide Sequence Data ◽  
Most Recent Common Ancestor ◽  
Y Chromosomes ◽  
Wide Range ◽  
Nominal Coverage ◽  
Biased Estimates

AbstractThis article proposes a method of estimating the time to the most recent common ancestor (TMRCA) of a sample of DNA sequences. The method is based on the molecular clock hypothesis, but avoids assumptions about population structure. Simulations show that in a wide range of situations, the point estimate has small bias and the confidence interval has at least the nominal coverage probability. We discuss conditions that can lead to biased estimates. Performance of this estimator is compared with existing methods based on the coalescence theory. The method is applied to sequences of Y chromosomes and mtDNAs to estimate the coalescent times of human male and female populations.

scholarly journals Solving the Fisher-Wright and coalescence problems with a discrete Markov chain analysis

2004 ◽  
Vol 36 (4) ◽  
pp. 1175-1197 ◽  
Author(s):  
Samuel R. Buss ◽  
Peter Clote
Keyword(s):  
Markov Chain ◽  
Recent Common Ancestor ◽  
Extinction Time ◽  
Markov Chain Analysis ◽  
Expected Time ◽  
Most Recent Common Ancestor ◽  
Chain Analysis ◽  
Wide Range ◽  
Mean Time ◽  
Discrete Markov Chain

We develop a new, self-contained proof that the expected number of generations required for gene allele fixation or extinction in a population of size n is O(n) under general assumptions. The proof relies on a discrete Markov chain analysis. We further develop an algorithm to compute expected fixation or extinction time to any desired precision. Our proofs establish O(nH(p)) as the expected time for gene allele fixation or extinction for the Fisher-Wright problem, where the gene occurs with initial frequency p and H(p) is the entropy function. Under a weaker hypothesis on the variance, the expected time is O(n(p(1-p))1/2) for fixation or extinction. Thus, the expected-time bound of O(n) for fixation or extinction holds in a wide range of situations. In the multi-allele case, the expected time for allele fixation or extinction in a population of size n with n distinct alleles is shown to be O(n). From this, a new proof is given of a coalescence theorem about the mean time to the most recent common ancestor (MRCA), which applies to a broad range of reproduction models satisfying our mean and weak variation conditions.

scholarly journals Population divergence time estimation using individual lineage label switching

2019 ◽  
Author(s):  
Peter Beerli ◽  
Haleh Ashki ◽  
Somayeh Mashayekhi ◽  
Michal Palczewski
Keyword(s):  
Divergence Time ◽  
Time Estimation ◽  
Random Variable ◽  
Recent Common Ancestor ◽  
Population Divergence ◽  
Inference Method ◽  
Divergence Time Estimation ◽  
Most Recent Common Ancestor ◽  
Wide Range ◽  
Truncated Normal

AbstractDivergence time estimation from multilocus genetic data has become common in population genetics and phylogenetics. We present a new Bayes inference method that treats the divergence time as a random variable. The divergence time is calculated from an assembly of splitting events on individual lineages in a genealogy. The waiting time for such a splitting event is drawn from a hazard function of the truncated normal distribution. This allows easy integration into the standard coalescence framework used in programs such as MIGRATE. We explore the accuracy of the new inference method with simulated population splittings over a wide range of divergence time values and with a dataset of the Zika virus; the geographic analyses of the expansion of the pathogen follows a trajectory from Africa to Asia to America, corroborating analyses based only on the dates of incidences. Evaluations of simple divergence models show high accuracy, whereas the accuracy of the results of isolation with migration (IM) models depend on the magnitude of the immigration rate and potentially on the number of samples. High immigration rates lead to a time of the most recent common ancestor of the sample that predates the divergence time, thus loses any potential signal of the divergence event in the sample data. This reduced accuracy with high immigration rates is problematic for all IM methods, including ours.

scholarly journals An accurate genetic clock

2015 ◽  
Author(s):  
David H Hamilton
Keyword(s):  
Stochastic Process ◽  
Kin Selection ◽  
Common Ancestor ◽  
Mutation Rates ◽  
Recent Common Ancestor ◽  
Molecular Clocks ◽  
Most Recent Common Ancestor ◽  
Wide Range ◽  
Short And Long Term

Molecular clocks give ``Time to most recent common ancestor'' TMRCA} of genetic trees. By Watson-Galton most lineages terminate, with a few overrepresented singular lineages generated by W. Hamilton's ``kin selection''. Applying current methods to this non-uniform branching produces greatly exaggerated TMRCA. We introduce an inhomogenous stochastic process which detects singular lineages by asymmetries, whose reduction gives true TMRCA. This implies a new method for computing mutation rates. Despite low rates similar to mitosis data, reduction implies younger TMRCA, with smaller errors. We establish accuracy by a comparison across a wide range of time, indeed this is only clock giving consistent results for both short and long term times. In particular we show that the dominant European y-haplotypes R1a1a & R1b1a2, expand from c3700BC, not reaching Anatolia before c3300BC. While this contradicts current clocks which date R1b1a2 to either the Neolithic Near East$ or Paleo-Europe, our dates support recent genetic analysis of ancient skeletons by Reich.

Numerical study of the effect of blockage ratio in forced convection confined flows of shear-thinning fluids

2021 ◽  
Vol 929 ◽  
Author(s):  
O. Ruz ◽  
E. Castillo ◽  
M. Cruchaga
Keyword(s):  
Case Studies ◽  
Power Law ◽  
Numerical Study ◽  
Three Dimensional ◽  
Shear Thinning ◽  
Time Dependent ◽  
Blockage Ratio ◽  
Chaotic Flows ◽  
Nusselt Numbers ◽  
Wide Range

In this work, the fluid dynamics and heat transfer of time-dependent flows with shear-thinning behaviour over two confined square cylinders in tandem arrangement are studied numerically. The case studies include two- and three-dimensional flows under a wide range of power-law indices, $0.25\leq n \leq 1.0$ , and blockage ratios, $\beta =0.50$ , 0.66 and 0.80, for a fixed Reynolds number of $Re=100$ and Prandtl number of $Pr=10$ . The fluid dynamic analysis includes detailed qualitative and quantitative comparisons between the different fluids and blockage ratios, where streamlines, viscosity fields, and lift and drag coefficients are presented. Moreover, a detailed study of the route from laminar time-dependent to chaotic flows is included. It was determined that the flow exhibits a transition from laminar to chaotic by decreasing the power-law index ( $n$ ) and increasing the blockage ratio ( $\beta$ ). With respect to the thermal analysis, isotherms and Nusselt numbers are compared between the different case studies. This analysis demonstrates that the average Nusselt numbers increased in chaotic flows. The three-dimensional cases confirmed the results proposed for the two-dimensional case.

scholarly journals Solving the Fisher-Wright and coalescence problems with a discrete Markov chain analysis

2004 ◽  
Vol 36 (04) ◽  
pp. 1175-1197 ◽  
Author(s):  
Samuel R. Buss ◽  
Peter Clote
Keyword(s):  
Markov Chain ◽  
Recent Common Ancestor ◽  
Extinction Time ◽  
Markov Chain Analysis ◽  
Expected Time ◽  
Most Recent Common Ancestor ◽  
Chain Analysis ◽  
Wide Range ◽  
Mean Time ◽  
Discrete Markov Chain

We develop a new, self-contained proof that the expected number of generations required for gene allele fixation or extinction in a population of size n is O(n) under general assumptions. The proof relies on a discrete Markov chain analysis. We further develop an algorithm to compute expected fixation or extinction time to any desired precision. Our proofs establish O(nH(p)) as the expected time for gene allele fixation or extinction for the Fisher-Wright problem, where the gene occurs with initial frequency p and H(p) is the entropy function. Under a weaker hypothesis on the variance, the expected time is O(n(p(1-p))1/2) for fixation or extinction. Thus, the expected-time bound of O(n) for fixation or extinction holds in a wide range of situations. In the multi-allele case, the expected time for allele fixation or extinction in a population of size n with n distinct alleles is shown to be O(n). From this, a new proof is given of a coalescence theorem about the mean time to the most recent common ancestor (MRCA), which applies to a broad range of reproduction models satisfying our mean and weak variation conditions.

scholarly journals An Accurate Genetic Clock

2015 ◽  
Author(s):  
David H Hamilton
Keyword(s):  
Kin Selection ◽  
Common Ancestor ◽  
Mutation Rates ◽  
Recent Common Ancestor ◽  
Random Factor ◽  
Most Recent Common Ancestor ◽  
Wide Range ◽  
Almost All ◽  
First Time ◽  
Phylogenetic Method

Our method for “Time to most recent common ancestor” TMRCA of genetic trees for the first time deals with natural selection by apriori mathematics and not as a random factor. Bioprocesses such as “kin selection” generate a few overrepresented “singular lineages” while almost all other lineages terminate. This non-uniform branching gives greatly exaggerated TMRCA with current methods. Thus we introduce an inhomogenous stochastic process which will detect singular lineages by asymmetries, whose “reduction” then gives true TMRCA. This gives a new phylogenetic method for computing mutation rates, with results similar to “pedigree” (meiosis) data. Despite these low rates, reduction implies younger TMRCA, with smaller errors. We establish accuracy by a comparison across a wide range of time, indeed this is only y-clock giving consistent results for 500-15,000 ybp. In particular we show that the dominant European Y-haplotypes R1a1a & R1b1a2, expand from c4000BC, not reaching Anatolia before c3800BC. This contradicts previous clocks dating R1b1a2 to either the Neolithic Near East or Paleo-Europe. However our dates match R1a1a & R1b1a2 found in Yamnaya cemetaries of c3300BC by Nielsen et al (2015), Pääbo et al(2015), together proving R1a1a & R1b1a2 originates in the Russian Steppes.

scholarly journals Variation in the molecular clock of primates

2016 ◽  
Author(s):  
Priya Moorjani ◽  
Carlos Eduardo G. Amorim ◽  
Peter F. Arndt ◽  
Molly Przeworski
Keyword(s):  
Gene Conversion ◽  
Molecular Clock ◽  
Primate Evolution ◽  
Primate Species ◽  
Recent Common Ancestor ◽  
New World Monkeys ◽  
Substitution Rates ◽  
Cpg Sites ◽  
Most Recent Common Ancestor ◽  
Biased Gene Conversion

Events in primate evolution are often dated by assuming a "molecular clock", i.e., a constant rate of substitution per unit time, but the validity of this assumption remains unclear. Among mammals, it is well known that there exists substantial variation in yearly substitution rates. Such variation is to be expected from differences in life-history traits, suggesting that it should also be found among primates. Motivated by these considerations, we analyze whole genomes from ten primate species, including Old World Monkeys (OWMs), New World Monkeys (NWMs) and apes, focusing on putatively neutral autosomal sites and controlling for possible effects of biased gene conversion and methylation at CpG sites. We find that substitution rates are ~65% higher in lineages leading from the hominoid-NWM ancestor to NWMs than to apes. Within apes, rates are ~2% higher in chimpanzees and ~7% higher in the gorilla than in humans. Substitution types subject to biased gene conversion show no more variation among species than those not subject to it. Not all mutation types behave similarly, however: in particular, transitions at CpG sites exhibit a more clock-like behavior than do other types, presumably due to their non-replicative origin. Thus, not only the total rate, but also the mutational spectrum varies among primates. This finding suggests that events in primate evolution are most reliably dated using CpG transitions. Taking this approach, we estimate that the average time to the most recent common ancestor of human and chimpanzee is 12.1 million years and their split time 7.9 million years.

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