scholarly journals The effects of a deleterious mutation load on patterns of influenza A/H3N2's antigenic evolution in humans

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Katia Koelle ◽  
David A Rasmussen
Keyword(s):  
Influenza Virus ◽  
Genetic Linkage ◽  
Influenza A ◽  
Deleterious Mutation ◽  
Rna Virus ◽  
Phylogenetic Analyses ◽  
Molecular Pathways ◽  
Deleterious Mutations ◽  
Mutation Load ◽  
Antigenic Evolution

Recent phylogenetic analyses indicate that RNA virus populations carry a significant deleterious mutation load. This mutation load has the potential to shape patterns of adaptive evolution via genetic linkage to beneficial mutations. Here, we examine the effect of deleterious mutations on patterns of influenza A subtype H3N2's antigenic evolution in humans. By first analyzing simple models of influenza that incorporate a mutation load, we show that deleterious mutations, as expected, act to slow the virus's rate of antigenic evolution, while making it more punctuated in nature. These models further predict three distinct molecular pathways by which antigenic cluster transitions occur, and we find phylogenetic patterns consistent with each of these pathways in influenza virus sequences. Simulations of a more complex phylodynamic model further indicate that antigenic mutations act in concert with deleterious mutations to reproduce influenza's spindly hemagglutinin phylogeny, co-circulation of antigenic variants, and high annual attack rates.

scholarly journals Harmful mutation load in the mitochondrial genomes of cattle breeds

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Sankar Subramanian
Keyword(s):  
Population Size ◽  
Artificial Selection ◽  
Deleterious Mutation ◽  
Genetic Diseases ◽  
Mitochondrial Genomes ◽  
Deleterious Mutations ◽  
Founder Population ◽  
Mutation Load ◽  
Effective Population ◽  
Cattle Breeds

Abstract Objective Domestication of wild animals results in a reduction in the effective population size, and this could affect the deleterious mutation load of domesticated breeds. Furthermore, artificial selection will also contribute to the accumulation of deleterious mutations due to the increased rate of inbreeding among these animals. The process of domestication, founder population size, and artificial selection differ between cattle breeds, which could lead to a variation in their deleterious mutation loads. We investigated this using mitochondrial genome data from 364 animals belonging to 18 cattle breeds of the world. Results Our analysis revealed more than a fivefold difference in the deleterious mutation load among cattle breeds. We also observed a negative correlation between the breed age and the proportion of deleterious amino acid-changing polymorphisms. This suggests a proportionally higher deleterious SNPs in young breeds compared to older breeds. Our results highlight the magnitude of difference in the deleterious mutations present in the mitochondrial genomes of various breeds. The results of this study could be useful in predicting the rate of incidence of genetic diseases in different breeds.

scholarly journals The mutation load under tetrasomic inheritance and its consequences for the evolution of the selfing rate in autotetraploid species

1999 ◽  
Vol 74 (1) ◽  
pp. 31-42 ◽  
Author(s):  
J. RONFORT
Keyword(s):  
Inbreeding Depression ◽  
Deleterious Mutation ◽  
Stable State ◽  
Approximate Solutions ◽  
Balance Model ◽  
Deleterious Mutations ◽  
Selfing Rate ◽  
Mutation Load ◽  
Mean Fitness ◽  
The Mean

Single-locus equilibrium frequencies of a partially recessive deleterious mutation under the mutation–selection balance model are derived for partially selfing autotetraploid populations. Assuming multiplicative fitness interactions among loci, approximate solutions for the mean fitness and inbreeding depression values are also derived for the multiple locus case and compared with expectations for the diploid model. As in diploids, purging of deleterious mutations through consanguineous matings occurs in autotetraploid populations, i.e. the equilibrium mutation load is a decreasing function of the selfing rate. However, the variation of inbreeding depression with the selfing rate depends strongly on the dominance coefficients associated with the three heterozygous genotypes. Inbreeding depression can either increase or decrease with the selfing rate, and does not always vary monotonically. Expected issues for the evolution of the selfing rate consequently differ depending on the dominance coefficients. In some cases, expectations for the evolution of the selfing rate resemble expectations in diploids; but particular sets of dominance coefficients can be found that lead to either complete selfing or intermediate selfing rates as unique evolutionary stable state.

scholarly journals Spatiotemporal Distribution and Evolution of the A/H1N1 2009 Pandemic Influenza Virus in Pigs in France from 2009 to 2017: Identification of a Potential Swine-Specific Lineage

2018 ◽  
Vol 92 (24) ◽  
Author(s):  
Amélie Chastagner ◽  
Séverine Hervé ◽  
Emilie Bonin ◽  
Stéphane Quéguiner ◽  
Edouard Hirchaud ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Phylogenetic Analyses ◽  
Swine Influenza ◽  
H1n1 Influenza ◽  
Antigenic Drift ◽  
Influenza A Viruses ◽  
Evolutionary Patterns ◽  
Increased Risk ◽  
Na Sequences

ABSTRACT The H1N1 influenza virus responsible for the most recent pandemic in 2009 (H1N1pdm) has spread to swine populations worldwide while it replaced the previous seasonal H1N1 virus in humans. In France, surveillance of swine influenza A viruses in pig herds with respiratory outbreaks led to the detection of 44 H1N1pdm strains between 2009 and 2017, regardless of the season, and findings were not correlated with pig density. From these isolates, 17 whole-genome sequences were obtained, as were 6 additional hemagglutinin (HA)/neuraminidase (NA) sequences, in order to perform spatial and temporal analyses of genetic diversity and to compare evolutionary patterns of H1N1pdm in pigs to patterns for human strains. Following mutation accumulation and fixation over time, phylogenetic analyses revealed for the first time the divergence of a swine-specific genogroup within the H1N1pdm lineage. The divergence is thought to have occurred around 2011, although this was demonstrated only through strains isolated in 2015 to 2016 in the southern half of France. To date, these H1N1pdm swine strains have not been related to any increased virulence in swine herds and have not exhibited any antigenic drift compared to seasonal human strains. However, further monitoring is encouraged, as diverging evolutionary patterns in these two species, i.e., swine and humans, may lead to the emergence of viruses with a potentially higher risk to both animal and human health.IMPORTANCE Pigs are a “mixing vessel” for influenza A viruses (IAVs) because of their ability to be infected by avian and human IAVs and their propensity to facilitate viral genomic reassortment events. Also, as IAVs may evolve differently in swine and humans, pigs can become a reservoir for old human strains against which the human population has become immunologically naive. Thus, viruses from the novel swine-specific H1N1pdm genogroup may continue to diverge from seasonal H1N1pdm strains and/or from other H1N1pdm viruses infecting pigs and lead to the emergence of viruses that would not be covered by human vaccines and/or swine vaccines based on antigens closely related to the original H1N1pdm virus. This discovery confirms the importance of encouraging swine IAV monitoring because H1N1pdm swine viruses could carry an increased risk to both human and swine health in the future as a whole H1N1pdm virus or gene provider in subsequent reassortant viruses.

scholarly journals Genetic and Antigenic Evolution of European Swine Influenza A Viruses of HA-1C (Avian-Like) and HA-1B (Human-Like) Lineages in France from 2000 to 2018

Viruses ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1304
Author(s):  
Amélie Chastagner ◽  
Séverine Hervé ◽  
Stéphane Quéguiner ◽  
Edouard Hirchaud ◽  
Pierrick Lucas ◽  
...  
Keyword(s):  
Amino Acid ◽  
Influenza A ◽  
Phylogenetic Analyses ◽  
Swine Influenza ◽  
Amino Acid Sequences ◽  
Antigenic Drift ◽  
Influenza A Viruses ◽  
Double Deletion ◽  
Antigenic Evolution ◽  
Amino Acid Mutations

This study evaluated the genetic and antigenic evolution of swine influenza A viruses (swIAV) of the two main enzootic H1 lineages, i.e., HA-1C (H1av) and -1B (H1hu), circulating in France between 2000 and 2018. SwIAV RNAs extracted from 1220 swine nasal swabs were hemagglutinin/neuraminidase (HA/NA) subtyped by RT-qPCRs, and 293 virus isolates were sequenced. In addition, 146 H1avNy and 105 H1huNy strains were submitted to hemagglutination inhibition tests. H1avN1 (66.5%) and H1huN2 (25.4%) subtypes were predominant. Most H1 strains belonged to HA-1C.2.1 or -1B.1.2.3 clades, but HA-1C.2, -1C.2.2, -1C.2.3, -1B.1.1, and -1B.1.2.1 clades were also detected sporadically. Within HA-1B.1.2.3 clade, a group of strains named “Δ146-147” harbored several amino acid mutations and a double deletion in HA, that led to a marked antigenic drift. Phylogenetic analyses revealed that internal segments belonged mainly to the “Eurasian avian-like lineage”, with two distinct genogroups for the M segment. In total, 17 distinct genotypes were identified within the study period. Reassortments of H1av/H1hu strains with H1N1pdm virus were rarely evidenced until 2018. Analysis of amino acid sequences predicted a variability in length of PB1-F2 and PA-X proteins and identified the appearance of several mutations in PB1, PB1-F2, PA, NP and NS1 proteins that could be linked to virulence, while markers for antiviral resistance were identified in N1 and N2. Altogether, diversity and evolution of swIAV recall the importance of disrupting the spreading of swIAV within and between pig herds, as well as IAV inter-species transmissions.

scholarly journals Direct RNA Sequencing of the Complete Influenza A Virus Genome

2018 ◽  
Author(s):  
Matthew W. Keller ◽  
Benjamin L. Rambo-Martin ◽  
Malania M. Wilson ◽  
Callie A. Ridenour ◽  
Samuel S. Shepard ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Splice Variants ◽  
Rna Virus ◽  
Allantoic Fluid ◽  
Virus Genome ◽  
Chemical Degradation ◽  
Original Form ◽  
Sequencing Platform ◽  
Oxford Nanopore

ABSTRACTFor the first time, a complete genome of an RNA virus has been sequenced in its original form. Previously, RNA was sequenced by the chemical degradation of radiolabelled RNA, a difficult method that produced only short sequences. Instead, RNA has usually been sequenced indirectly by copying it into cDNA, which is often amplified to dsDNA by PCR and subsequently analyzed using a variety of DNA sequencing methods. We designed an adapter to short highly conserved termini of the influenza virus genome to target the (-) sense RNA into a protein nanopore on the Oxford Nanopore MinION sequencing platform. Utilizing this method and total RNA extracted from the allantoic fluid of infected chicken eggs, we demonstrate successful sequencing of the complete influenza virus genome with 100% nucleotide coverage, 99% consensus identity, and 99% of reads mapped to influenza. By utilizing the same methodology we can redesign the adapter in order to expand the targets to include viral mRNA and (+) sense cRNA, which are essential to the viral life cycle. This has the potential to identify and quantify splice variants and base modifications, which are not practically measurable with current methods.

scholarly journals Characterization of the 1918 “Spanish” Influenza Virus Matrix Gene Segment

2002 ◽  
Vol 76 (21) ◽  
pp. 10717-10723 ◽  
Author(s):  
Ann H. Reid ◽  
Thomas G. Fanning ◽  
Thomas A. Janczewski ◽  
Sherman McCall ◽  
Jeffery K. Taubenberger
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Rna Binding ◽  
Transmembrane Domain ◽  
Phylogenetic Analyses ◽  
Gene Segment ◽  
High Yield ◽  
Coding Region ◽  
Matrix Gene ◽  
Virus Strains

ABSTRACT The coding region of influenza A virus RNA segment 7 from the 1918 pandemic virus, consisting of the open reading frames of the two matrix genes M1 and M2, has been sequenced. While this segment is highly conserved among influenza virus strains, the 1918 sequence does not match any previously sequenced influenza virus strains. The 1918 sequence matches the consensus over the M1 RNA-binding domains and nuclear localization signal and the highly conserved transmembrane domain of M2. Amino acid changes that correlate with high yield and pathogenicity in animal models were not found in the 1918 strain. Phylogenetic analyses suggest that both genes were mammalian adapted and that the 1918 sequence is very similar to the common ancestor of all subsequent human and classical swine matrix segments. The 1918 sequence matches other mammalian strains at 4 amino acids in the extracellular domain of M2 that differ consistently between avian and mammalian strains, suggesting that the matrix segment may have been circulating in human strains for at least several years before 1918.

scholarly journals Evolution and Molecular Epidemiology of H9N2 Influenza A Viruses from Quail in Southern China, 2000 to 2005

2006 ◽  
Vol 81 (6) ◽  
pp. 2635-2645 ◽  
Author(s):  
K. M. Xu ◽  
K. S. Li ◽  
G. J. D. Smith ◽  
J. W. Li ◽  
H. Tai ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Southern China ◽  
Phylogenetic Analyses ◽  
Influenza Viruses ◽  
Influenza A Viruses ◽  
Laboratory Findings ◽  
Virus Surveillance ◽  
Important Host ◽  
Pandemic Strains

ABSTRACT H9N2 influenza viruses have become established and maintain long-term endemicity in terrestrial poultry in Asian countries. Occasionally these viruses transmit to other mammals, including humans. Increasing epidemiological and laboratory findings suggest that quail may be an important host, as they are susceptible to different subtypes of influenza viruses. To better understand the role of quail in influenza virus ecology and evolution, H9N2 viruses isolated from quail during 2000 to 2005 were antigenically and genetically characterized. Our results showed that H9N2 viruses are prevalent year-round in southern China and replicate mainly asymptomatically in the respiratory tract of quail. Genetic analysis revealed that both the G1-like and Ck/Bei-like H9N2 lineages were cocirculating in quail since 2000. Phylogenetic analyses demonstrated that most of the isolates tested were double- or multiple-reassortant variants, with four G1-like and 16 Ck/Bei-like genotypes recognized. A novel genotype of G1-like virus became predominant in quail since 2003, while multiple Ck/Bei-like genotypes were introduced into quail, wherein they incorporated G1-like gene segments, but none of them became established in this host. Those Ck/Bei-like reassortants generated in quail have then been introduced into other poultry. These complex interactions form a two-way transmission system between quail and other types of poultry. The present study provides evidence that H9N2 and H5N1 subtype viruses have also exchanged gene segments to generate currently circulating reassortants of both subtypes that have pandemic potential. Continuing influenza virus surveillance in poultry is critical to understanding the genesis and emergence of potentially pandemic strains in this region.

scholarly journals A deleterious mutation-sheltering theory for the evolution of sex chromosomes and supergenes

2021 ◽  
Author(s):  
Paul Jay ◽  
Tatiana Giraud ◽  
Emilie Tezenas
Keyword(s):  
Mathematical Modeling ◽  
Sex Chromosomes ◽  
Deleterious Mutation ◽  
Stochastic Simulations ◽  
Recessive Mutation ◽  
Deleterious Mutations ◽  
Evolution Of Sex ◽  
Mutation Load ◽  
Recombination Suppression ◽  
Chromosomal Inversions

Many organisms have sex chromosomes with large non-recombining regions having expanded stepwise, the reason why being still poorly understood. Theories proposed so far rely on differences between sexes but are poorly supported by empirical data and cannot account for the stepwise suppression of recombination around sex chromosomes in organisms without sexual dimorphism. We show here, by mathematical modeling and stochastic simulations, that recombination suppression in sex chromosomes can evolve simply because it shelters recessive deleterious mutations, which are ubiquitous in genomes. The permanent heterozygosity of sex-determining alleles protects linked chromosomal inversions against expression of their recessive mutation load, leading to an accumulation of inversions around these loci, as observed in nature. We provide here a testable and widely applicable theory to explain the evolution of sex chromosomes and of supergenes in general.

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