Phylogenomic analysis of SARS-CoV-2 genomes from western India reveals unique linked mutations

2020 ◽  
Author(s):  
Dhiraj Paul ◽  
Kunal Jani ◽  
Janesh Kumar ◽  
Radha Chauhan ◽  
Vasudevan Seshadri ◽  
...  
Keyword(s):  
Evolutionary Dynamics ◽  
Fitness Landscape ◽  
Geographical Location ◽  
Specific Pattern ◽  
Distinct Pattern ◽  
Viral Fitness ◽  
Phylogenomic Analysis ◽  
Western India ◽  
Asymptomatic Patients ◽  
Major Cluster

AbstractIndia has become the third worst-hit nation by the COVID-19 pandemic caused by the SARS-CoV-2 virus. Here, we investigated the molecular, phylogenomic, and evolutionary dynamics of SARS-CoV-2 in western India, the most affected region of the country. A total of 90 genomes were sequenced. Four nucleotide variants, namely C241T, C3037T, C14408T (Pro4715Leu), and A23403G (Asp614Gly), located at 5’UTR, Orf1a, Orf1b, and Spike protein regions of the genome, respectively, were predominant and ubiquitous (90%). Phylogenetic analysis of the genomes revealed four distinct clusters, formed owing to different variants. The major cluster (cluster 4) is distinguished by mutations C313T, C5700A, G28881A are unique patterns and observed in 45% of samples. We thus report a newly emerging pattern of linked mutations. The predominance of these linked mutations suggests that they are likely a part of the viral fitness landscape. A novel and distinct pattern of mutations in the viral strains of each of the districts was observed. The Satara district viral strains showed mutations primarily at the 3′ end of the genome, while Nashik district viral strains displayed mutations at the 5′ end of the genome. Characterization of Pune strains showed that a novel variant has overtaken the other strains. Examination of the frequency of three mutations i.e., C313T, C5700A, G28881A in symptomatic versus asymptomatic patients indicated an increased occurrence in symptomatic cases, which is more prominent in females. The age-wise specific pattern of mutation is observed. Mutations C18877T, G20326A, G24794T, G25563T, G26152T, and C26735T are found in more than 30% study samples in the age group of 10-25. Intriguingly, these mutations are not detected in the higher age range 61-80. These findings portray the prevalence of unique linked mutations in SARS-CoV-2 in western India and their prevalence in symptomatic patients.ImportanceElucidation of the SARS-CoV-2 mutational landscape within a specific geographical location, and its relationship with age and symptoms, is essential to understand its local transmission dynamics and control. Here we present the first comprehensive study on genome and mutation pattern analysis of SARS-CoV-2 from the western part of India, the worst affected region by the pandemic. Our analysis revealed three unique linked mutations, which are prevalent in most of the sequences studied. These may serve as a molecular marker to track the spread of this viral variant to different places.

scholarly journals Stabilising selection causes grossly altered but stable karyotypes in metastatic colorectal cancer

2020 ◽  
Author(s):  
William Cross ◽  
Maximilian Mossner ◽  
Salpie Nowinski ◽  
George Cresswell ◽  
Abhirup Banerjee ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cell ◽  
Cell Biology ◽  
Evolutionary Dynamics ◽  
Fitness Landscape ◽  
Primary Tumour ◽  
Genomic Analysis ◽  
Specific Pattern ◽  
Metastatic Lesions ◽  
Stabilising Selection

AbstractAneuploidy, defined as the loss and gain of whole and part chromosomes, is a near-ubiquitous feature of cancer genomes, is prognostic, and likely an important determinant of cancer cell biology. In colorectal cancer (CRC), aneuploidy is found in virtually all tumours, including precursor adenomas. However, the temporal evolutionary dynamics that select for aneuploidy remain broadly uncharacterised. Here we perform genomic analysis of 755 samples from a total of 167 patients with colorectal-derived neoplastic lesions that cross-sectionally represent the distinct stages of tumour evolution, and longitudinally track individual tumours through metastasis and treatment. Precancer lesions (adenomas) exhibited low levels of aneuploidy but high intra-tumour heterogeneity, whereas cancers had high aneuploidy but low heterogeneity, indicating that progression is through a genetic bottleneck that suppresses diversity. Individual CRC glands from the same tumour have similar karyotypes, despite prior evidence of ongoing instability at the cell level. Pseudo-stable aneuploid genomes were observed in metastatic lesions sampled from liver and other organs, after chemo- or targeted therapies, and late recurrences detected many years after the diagnosis of a primary tumour. Modelling indicates that these data are consistent with the action of stabilising selection that ‘traps’ cancer cell genomes on a fitness peak defined by the specific pattern of aneuploidy. These data show that the initial progression of CRC requires the traversal of a rugged fitness landscape and subsequent genomic evolution, including metastatic dissemination and therapeutic resistance, is constrained by stabilising selection.

scholarly journals Long-Term Cocirculation of Two Strains of Pepino Mosaic Virus in Tomato Crops and Its Effect on Population Genetic Variability

2020 ◽  
Vol 110 (1) ◽  
pp. 49-57 ◽  
Author(s):  
C. Alcaide ◽  
M. P. Rabadán ◽  
M. Juárez ◽  
P. Gómez
Keyword(s):  
Genetic Variability ◽  
Mosaic Virus ◽  
Evolutionary Dynamics ◽  
Geographical Area ◽  
Viral Fitness ◽  
Mixed Infections ◽  
Supporting Evidence ◽  
Pepino Mosaic Virus ◽  
Nucleotide Variability

Mixed viral infections are common in plants, and the evolutionary dynamics of viral populations may differ depending on whether the infection is caused by single or multiple viral strains. However, comparative studies of single and mixed infections using viral populations in comparable agricultural and geographical locations are lacking. Here, we monitored the occurrence of pepino mosaic virus (PepMV) in tomato crops in two major tomato-producing areas in Murcia (southeastern Spain), supporting evidence showing that PepMV disease-affected plants had single infections of the Chilean 2 (CH2) strain in one area and the other area exhibited long-term (13 years) coexistence of the CH2 and European (EU) strains. We hypothesized that circulating strains of PepMV might be modulating the differentiation between them and shaping the evolutionary dynamics of PepMV populations. Our phylogenetic analysis of 106 CH2 isolates randomly selected from both areas showed a remarkable divergence between the CH2 isolates, with increased nucleotide variability in the geographical area where both strains cocirculate. Furthermore, the potential virus–virus interaction was studied further by constructing six full-length infectious CH2 clones from both areas, and assessing their viral fitness in the presence and absence of an EU-type isolate. All CH2 clones showed decreased fitness in mixed infections and although complete genome sequencing indicated a nucleotide divergence of those CH2 clones by area, the magnitude of the fitness response was irrespective of the CH2 origin. Overall, these results suggest that although agroecological cropping practices may be particularly important for explaining the evolutionary dynamics of PepMV in tomato crops, the cocirculation of both strains may have implications on the genetic variability of PepMV populations.

scholarly journals Environmental changes dictate selection and nonspecific epistasis in an empirical phenotype-environment-fitness landscape

2021 ◽  
Author(s):  
J.Z. Chen ◽  
D.M. Fowler ◽  
N. Tokuriki
Keyword(s):  
Selection Pressure ◽  
Evolutionary Dynamics ◽  
Environmental Changes ◽  
Fitness Landscape ◽  
Resistance Level ◽  
Phenotypic Changes ◽  
Environmental Selection ◽  
Selection Environment ◽  
Data Points ◽  
Environmental Dependence

SummaryThe fitness landscape, a function that maps genotypic and phenotypic changes to their effects on fitness, is an invaluable concept in evolutionary biochemistry. Though widely discussed, measurements of phenotype-fitness landscapes in proteins remain scarce. Here, we quantify all single mutational effects on fitness and phenotype (antibiotic resistance level) of VIM-2 β-lactamase (5600 variants) across a 64-fold range of ampicillin concentrations by deep mutational scanning. We then construct a phenotype-fitness landscape that takes variations in environmental selection pressure into account (a phenotype-environment-fitness landscape). We found that a simple, empirical landscape accurately models the ~39,000 mutational data points, which suggests the evolution of VIM-2 can be predicted based on the selection environment. Our landscape provides new quantitative knowledge on the evolution of the β-lactamases and proteins in general, particularly their evolutionary dynamics under sub-inhibitory antibiotic concentrations, as well as the mechanisms and environmental dependence of nonspecific epistasis.

scholarly journals The distribution of epistasis on simple fitness landscapes

2018 ◽  
Author(s):  
Christelle Fraïsse ◽  
John J. Welch
Keyword(s):  
Evolutionary Dynamics ◽  
Fitness Landscape ◽  
Null Model ◽  
Large Data ◽  
Fitness Landscapes ◽  
Mutational Bias ◽  
Data Set ◽  
Epistatic Interactions ◽  
Standing Variation ◽  
Mean And Variance

AbstractFitness interactions between mutations can influence a population’s evolution in many different ways. While epistatic effects are difficult to measure precisely, important information about the overall distribution is captured by the mean and variance of log fitnesses for individuals carrying different numbers of mutations. We derive predictions for these quantities from simple fitness landscapes, based on models of optimizing selection on quantitative traits. We also explore extensions to the models, including modular pleiotropy, variable effects sizes, mutational bias, and maladaptation of the wild-type. We illustrate our approach by reanalysing a large data set of mutant effects in a yeast snoRNA. Though characterized by some strong epistatic interactions, these data give a good overall fit to the non-epistatic null model, suggesting that epistasis might have little effect on the evolutionary dynamics in this system. We also show how the amount of epistasis depends on both the underlying fitness landscape, and the distribution of mutations, and so it is expected to vary in consistent ways between new mutations, standing variation, and fixed mutations.

scholarly journals Evolution during primary HIV infection does not require adaptive immune selection

2020 ◽  
Author(s):  
David A Swan ◽  
Morgane Rolland ◽  
Joshua Herbeck ◽  
Joshua T Schiffer ◽  
Daniel B Reeves
Keyword(s):  
Viral Load ◽  
Immune System ◽  
Hiv Infection ◽  
Evolutionary Dynamics ◽  
Immune Cell ◽  
Adaptive Immune System ◽  
Viral Fitness ◽  
Immune Cell Population ◽  
Adaptive Immune

AbstractModern HIV research depends crucially on both viral sequencing and population measurements. To directly link mechanistic biological processes and evolutionary dynamics during HIV infection, we developed multiple within-host phylodynamic (wi-phy) models of HIV primary infection for comparative validation against viral load and evolutionary dynamics data. The most parsimonious and accurate model required no positive selection, suggesting that the host adaptive immune system reduces viral load, but does not drive observed viral evolution. Rather, random genetic drift primarily dictates fitness changes. These results hold during early infection, and even during chronic infection when selection has been observed, viral fitness distributions are not largely different from in vitro distributions that emerge without adaptive immunity. These results highlight how phylogenetic inference must consider complex viral and immune-cell population dynamics to gain accurate mechanistic insights.One sentence summaryThrough the lens of a unified population and phylodynamic model, current data show the first wave of HIV mutations are not driven by selection by the adaptive immune system.

scholarly journals The distribution of epistasis on simple fitness landscapes

2019 ◽  
Vol 15 (4) ◽  
pp. 20180881 ◽  
Author(s):  
Christelle Fraïsse ◽  
John J. Welch
Keyword(s):  
Evolutionary Dynamics ◽  
Fitness Landscape ◽  
Null Model ◽  
Fitness Landscapes ◽  
Mutational Bias ◽  
Variable Effect ◽  
Epistatic Effects ◽  
Standing Variation ◽  
Mean And Variance ◽  
Nucleolar Rna

Fitness interactions between mutations can influence a population’s evolution in many different ways. While epistatic effects are difficult to measure precisely, important information is captured by the mean and variance of log fitnesses for individuals carrying different numbers of mutations. We derive predictions for these quantities from a class of simple fitness landscapes, based on models of optimizing selection on quantitative traits. We also explore extensions to the models, including modular pleiotropy, variable effect sizes, mutational bias and maladaptation of the wild type. We illustrate our approach by reanalysing a large dataset of mutant effects in a yeast snoRNA (small nucleolar RNA). Though characterized by some large epistatic effects, these data give a good overall fit to the non-epistatic null model, suggesting that epistasis might have limited influence on the evolutionary dynamics in this system. We also show how the amount of epistasis depends on both the underlying fitness landscape and the distribution of mutations, and so is expected to vary in consistent ways between new mutations, standing variation and fixed mutations.

Biophysical determinants of mutational robustness in a viral molecular fitness landscape

2017 ◽  
Author(s):  
Manasi A. Pethe ◽  
Aliza B. Rubenstein ◽  
Dmitri Zorine ◽  
Sagar D. Khare
Keyword(s):  
Fitness Landscape ◽  
Rna Virus ◽  
Fitness Landscapes ◽  
Viral Fitness ◽  
Mutational Robustness ◽  
Hcv Protease ◽  
Viral Polyprotein ◽  
Biophysical Interactions ◽  
Proteins And Peptides

Biophysical interactions between proteins and peptides are key determinants of genotype-fitness landscapes, but an understanding of how molecular structure and residue-level energetics at protein-peptide interfaces shape functional landscapes remains elusive. Combining information from yeast-based library screening, next-generation sequencing and structure-based modeling, we report comprehensive sequence-energetics-function mapping of the specificity landscape of the Hepatitis C Virus (HCV) NS3/4A protease, whose function — site-specific cleavages of the viral polyprotein — is a key determinant of viral fitness. We elucidate the cleavability of 3.2 million substrate variants by the HCV protease and find extensive clustering of cleavable and uncleavable motifs in sequence space indicating mutational robustness, and thereby providing a plausible molecular mechanism to buffer the effects of low replicative fidelity of this RNA virus. Specificity landscapes of known drug-resistant variants are similarly clustered. Our results highlight the key and constraining role of molecular-level energetics in shaping plateau-like fitness landscapes from quasispecies theory.

scholarly journals The evolutionary dynamics of influenza A virus adaptation to mammalian hosts

2013 ◽  
Vol 368 (1614) ◽  
pp. 20120382 ◽  
Author(s):  
S. Bhatt ◽  
T. T. Lam ◽  
S. J. Lycett ◽  
A. J. Leigh Brown ◽  
T. A. Bowden ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Adaptive Evolution ◽  
Influenza A ◽  
Evolutionary Dynamics ◽  
Adaptive Dynamics ◽  
Swine Influenza ◽  
Influenza Viruses ◽  
Viral Fitness ◽  
Influenza A Viruses ◽  
Entire Genome

Few questions on infectious disease are more important than understanding how and why avian influenza A viruses successfully emerge in mammalian populations, yet little is known about the rate and nature of the virus’ genetic adaptation in new hosts. Here, we measure, for the first time, the genomic rate of adaptive evolution of swine influenza viruses (SwIV) that originated in birds. By using a curated dataset of more than 24 000 human and swine influenza gene sequences, including 41 newly characterized genomes, we reconstructed the adaptive dynamics of three major SwIV lineages (Eurasian, EA; classical swine, CS; triple reassortant, TR). We found that, following the transfer of the EA lineage from birds to swine in the late 1970s, EA virus genes have undergone substantially faster adaptive evolution than those of the CS lineage, which had circulated among swine for decades. Further, the adaptation rates of the EA lineage antigenic haemagglutinin and neuraminidase genes were unexpectedly high and similar to those observed in human influenza A. We show that the successful establishment of avian influenza viruses in swine is associated with raised adaptive evolution across the entire genome for many years after zoonosis, reflecting the contribution of multiple mutations to the coordinated optimization of viral fitness in a new environment. This dynamics is replicated independently in the polymerase genes of the TR lineage, which established in swine following separate transmission from non-swine hosts.

scholarly journals Detecting mosaic patterns in macroevolutionary disparity

2018 ◽  
Author(s):  
Caroline Parins-Fukuchi
Keyword(s):  
Evolutionary Dynamics ◽  
Distinct Pattern ◽  
The Body ◽  
Phenotypic Trait ◽  
Multiple Traits ◽  
Mosaic Pattern ◽  
Phenotypic Data ◽  
Evolutionary Patterns ◽  
Multidimensional Datasets ◽  
Evolutionary Distinctiveness

ABSTRACTEvolutionary biologists have long sought to understand the full complexity in pattern and process that shapes organismal diversity. Although phylogenetic comparative methods are often used to reconstruct complex evolutionary dynamics, they are typically limited to a single phenotypic trait. Extensions that accommodate multiple traits lack the ability to partition multidimensional datasets into a set of mosaic suites of evolutionarily linked characters. I introduce a comparative framework that identifies heterogeneity in evolutionary patterns across large datasets of continuous traits. Using a model of continuous trait evolution based on the differential accumulation of disparity across lineages in a phylogeny, the approach algorithmically partitions traits into a set of character suites that best explains the data, where each suite displays a distinct pattern in phylogenetic morphological disparity. When applied to empirical data, the approach revealed a mosaic pattern predicted by developmental biology. The evolutionary distinctiveness of individual suites can be investigated in more detail, either by fitting conventional comparative models or by directly studying the phylogenetic patterns in disparity recovered during the analysis. This framework can supplement existing comparative approaches by inferring the complex, integrated patterns that shape evolution across the body plan from disparate developmental, morphometric, and environmental sources of phenotypic data.

scholarly journals Fitness estimation for viral variants in the context of cellular coinfection

2021 ◽  
Author(s):  
Huisheng Zhu ◽  
Brent E Allman ◽  
Katia Koelle
Keyword(s):  
Evolutionary Dynamics ◽  
Sequence Data ◽  
Population Level ◽  
Viral Fitness ◽  
Fitness Effects ◽  
Fitness Advantage ◽  
Viral Adaptation ◽  
Zoonotic Viruses ◽  
Frequency Changes

AbstractAnimal models are frequently used to characterize the within-host dynamics of emerging zoonotic viruses. More recent studies have also deep-sequenced longitudinal viral samples originating from experimental challenges to gain a better understanding of how these viruses may evolve in vivo and between transmission events. These studies have often identified nucleotide variants that can replicate more efficiently within hosts and also transmit more effectively between hosts. Quantifying the degree to which a mutation impacts viral fitness within a host can improve identification of variants that are of particular epidemiological concern and our ability to anticipate viral adaptation at the population level. While methods have been developed to quantify the fitness effects of mutations using observed changes in allele frequencies over the course of a host’s infection, none of the existing methods account for the possibility of cellular coinfection. Here, we develop mathematical models to project variant allele frequency changes in the context of cellular coinfection and, further, integrate these models with statistical inference approaches to demonstrate how variant fitness can be estimated alongside cellular multiplicity of infection. We apply our approaches to empirical longitudinally-sampled H5N1 sequence data from ferrets. Our results indicate that previous studies may have significantly underestimated the within-host fitness advantage of viral variants. These findings underscore the importance of considering the process of cellular coinfection when studying within-host viral evolutionary dynamics.

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