Browsing by Subject "Genome evolution"

Now showing 1 - 4 of 4
  • Thumbnail Image
    Item
    Open Access
    Avoidance of Protein Fold Disruption in Natural Virus Recombinants
    (Public Library of Science, 2007) Lefeuvre, Pierre; Lett, Jean-Michel; Reynaud, Bernard; Martin, Darren P
    Author Summary The exchange of genetic material between different virus species, called inter-species recombination, has the potential to generate, within a single genome replication cycle, an almost unimaginable number of genetically distinct virus strains, including many that might cause deadly new human, animal, or plant diseases. Many fear that inter-species recombination could provide viruses with quick access to evolutionary innovations such as broader host ranges, altered tissue tropisms, or increased severities. However, mounting evidence suggests that recombination is not an unconstrained process and that most inter-species recombinants that occur in nature are probably defective. It is suspected that networks of coevolved interactions between different parts of virus genomes and their encoded proteins must be kept intact for newly formed inter-species recombinants to have any chance of out-competing their parents. One category of coevolved interaction is that between contacting amino acids within the 3-D structures of folded proteins. Here we examine the distributions of recombination events across the genomes of a group of rampantly recombining plant viruses and find very good evidence that this class of interaction tends to be preserved amongst recombinant sequences sampled from nature. This indicates that selection against misfolded proteins strongly influences the survival of natural recombinants.
  • Thumbnail Image
    Item
    Open Access
    The Evolutionary Value of Recombination Is Constrained by Genome Modularity
    (Public Library of Science, 2005) Martin, Darren P; Walt, Eric van der; Posada, David; Rybicki, Edward P
    Genetic recombination is a fundamental evolutionary mechanism promoting biological adaptation. Using engineered recombinants of the small single-stranded DNA plant virus, Maize streak virus (MSV), we experimentally demonstrate that fragments of genetic material only function optimally if they reside within genomes similar to those in which they evolved. The degree of similarity necessary for optimal functionality is correlated with the complexity of intragenomic interaction networks within which genome fragments must function. There is a striking correlation between our experimental results and the types of MSV recombinants that are detectable in nature, indicating that obligatory maintenance of intragenome interaction networks strongly constrains the evolutionary value of recombination for this virus and probably for genomes in general.
  • Thumbnail Image
    Item
    Open Access
    Genetic variability among complete human respiratory syncytial virus subgroup A genomes: bridging molecular evolutionary dynamics and epidemiology
    (Public Library of Science, 2012) Tan, Lydia; Lemey, Philippe; Houspie, Lieselot; Viveen, Marco C; Jansen, Nicolaas J G; Loon, Anton M van; Wiertz, Emmanuel; Bleek, Grada M van; Martin, Darren P; Coenjaerts, Frank E
    Human respiratory syncytial virus (RSV) is an important cause of severe lower respiratory tract infections in infants and the elderly. In the vast majority of cases, however, RSV infections run mild and symptoms resemble those of a common cold. The immunological, clinical, and epidemiological profile of severe RSV infections suggests a disease caused by a virus with typical seasonal transmission behavior, lacking clear-cut virulence factors, but instead causing disease by modifying the host's immune response in a way that stimulates pathogenesis. Yet, the interplay between RSV-evoked immune responses and epidemic behavior, and how this affects the genomic evolutionary dynamics of the virus, remains poorly understood. Here, we present a comprehensive collection of 33 novel RSV subgroup A genomes from strains sampled over the last decade, and provide the first measurement of RSV-A genomic diversity through time in a phylodynamic framework. In addition, we map amino acid substitutions per protein to determine mutational hotspots in specific domains. Using Bayesian genealogical inference, we estimated the genomic evolutionary rate to be 6.47×10 −4 (credible interval: 5.56×10 −4 , 7.38×10 −4 ) substitutions/site/year, considerably slower than previous estimates based on G gene sequences only. The G gene is however marked by elevated substitution rates compared to other RSV genes, which can be attributed to relaxed selective constraints. In line with this, site-specific selection analyses identify the G gene as the major target of diversifying selection. Importantly, statistical analysis demonstrates that the immune driven positive selection does not leave a measurable imprint on the genome phylogeny, implying that RSV lineage replacement mainly follows nonselective epidemiological processes. The roughly 50 years of RSV-A genomic evolution are characterized by a constant population size through time and general co-circulation of lineages over many epidemic seasons - a conclusion that might be taken into account when developing future therapeutic and preventive strategies.
  • Thumbnail Image
    Item
    Open Access
    Whole genome sequencing reveals complex evolution patterns of multidrug-resistant Mycobacterium tuberculosis Beijing strains in patients
    (Public Library of Science, 2013) Merker, Matthias; Kohl, Thomas A; Roetzer, Andreas; Truebe, Leona; Richter, Elvira; Rüsch-Gerdes, Sabine; Fattorini, Lanfranco; Oggioni, Marco R; Cox, Helen; Varaine, Francis
    Multidrug-resistant (MDR) Mycobacterium tuberculosis complex (MTBC) strains represent a major threat for tuberculosis (TB) control. Treatment of MDR-TB patients is long and less effective, resulting in a significant number of treatment failures. The development of further resistances leads to extensively drug-resistant (XDR) variants. However, data on the individual reasons for treatment failure, e.g. an induced mutational burst, and on the evolution of bacteria in the patient are only sparsely available. To address this question, we investigated the intra-patient evolution of serial MTBC isolates obtained from three MDR-TB patients undergoing longitudinal treatment, finally leading to XDR-TB. Sequential isolates displayed identical IS 6110 fingerprint patterns, suggesting the absence of exogenous re-infection. We utilized whole genome sequencing (WGS) to screen for variations in three isolates from Patient A and four isolates from Patient B and C, respectively. Acquired polymorphisms were subsequently validated in up to 15 serial isolates by Sanger sequencing. We determined eight (Patient A) and nine (Patient B) polymorphisms, which occurred in a stepwise manner during the course of the therapy and were linked to resistance or a potential compensatory mechanism. For both patients, our analysis revealed the long-term co-existence of clonal subpopulations that displayed different drug resistance allele combinations. Out of these, the most resistant clone was fixed in the population. In contrast, baseline and follow-up isolates of Patient C were distinguished each by eleven unique polymorphisms, indicating an exogenous re-infection with an XDR strain not detected by IS 6110 RFLP typing. Our study demonstrates that intra-patient microevolution of MDR-MTBC strains under longitudinal treatment is more complex than previously anticipated. However, a mutator phenotype was not detected. The presence of different subpopulations might confound phenotypic and molecular drug resistance tests. Furthermore, high resolution WGS analysis is necessary to accurately detect exogenous re-infection as classical genotyping lacks discriminatory power in high incidence settings.