Stronger selection can slow down evolution driven by recombination on a smooth fitness landscape.
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ABSTRACT:
SUBMITTER: Ueda M
PROVIDER: S-EPMC5557360 | biostudies-other | 2017
REPOSITORIES: biostudies-other
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Project description:BackgroundThe evolution of bacterial organelles involved in host-pathogen interactions is subject to intense and competing selective pressures due to the need to maintain function while escaping the host immune response. To characterize the interplay of these forces in an important pathogen, we sequenced the rlrA islet, a chromosomal region encoding for a pilus-like structure involved in adherence to lung epithelial cells in vitro and in colonization in a murine model of infection, in 44 clinical isolates of Streptococcus pneumoniae.ResultsWe found that the rrgA and rrgB genes, encoding the main structural components of the pilus, are under the action of positive selection. In contrast, the rrgC gene, coding for a component present in low quantities in the assembled pilus, and the srtB, srtC and srtD genes, coding for three sortase enzymes essential for pilus assembly but probably not directly exposed to the host immune system, show no evidence of positive selection. We found several events of homologous recombination in the region containing these genes, identifying 4 major recombination hotspots. An analysis of the most recent recombination events shows a high level of mosaicism of the region coding for the rrgC, srtB, srtC and srtD genes.ConclusionsIn the rlrA islet, the genes coding for proteins directly exposed to the host immune response are under the action of positive selection, and exist in distinct forms in the population of circulating strains. The genes coding for proteins not directly exposed on the surface of the bacterial cell are more conserved probably due to the homogenizing effect of recombination.
| S-EPMC2576445 | biostudies-literature
Project description:Meiotic recombination comprises crossovers and noncrossovers. Recombination, crossover in particular, shuffles mutations and impacts both the level of genetic polymorphism and the speed of adaptation. In many species, the recombination rate varies across the genome with hot and cold spots. The hotspot paradox hypothesis asserts that recombination hotspots are evolutionarily unstable due to self-destruction. However, the genomic landscape of double-strand breaks (DSBs), which initiate recombination, is evolutionarily conserved among divergent yeast species, casting doubt on the hotspot paradox hypothesis. Nonetheless, because only a subset of DSBs are associated with crossovers, the evolutionary conservation of the crossover landscape could differ from that of DSBs. Here, we investigate this possibility by generating a high-resolution recombination map of the budding yeast Saccharomyces paradoxus through whole-genome sequencing of 50 meiotic tetrads and by comparing this recombination map with that of S. cerevisiae. We observe a 40% lower recombination rate in S. paradoxus than in S. cerevisiae. Compared with the DSB landscape, the crossover landscape is even more conserved. Further analyses indicate that the elevated conservation of the crossover landscape is explained by a near-subtelomeric crossover preference in both yeasts, which we find to be attributable at least in part to crossover interference. We conclude that the yeast crossover landscape is highly conserved and that the evolutionary conservation of this landscape can differ from that of the DSB landscape.
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Project description:Effector proteins translocated by the Dot/Icm type IV secretion system determine the virulence of Legionella pneumophila (L. pneumophila). Among these effectors, members of the SidE family (SidEs) regulate several cellular processes through a unique phosphoribosyl ubiquitination mechanism mediated by another effector, SidJ. Host-cell calmodulin (CaM) activates SidJ to glutamylate the SidEs of ubiquitin (Ub) ligases and to make a balanced Ub ligase activity. Given the central role of SidJ in this regulatory process, studying the nature of evolution of sidJ is important to understand the virulence of L. pneumophila and the interaction between the bacteria and its hosts. By studying sidJ from a large number of L. pneumophila strains and using various molecular evolution algorithms, we demonstrated that intragenic recombination drove the evolution of sidJ and contributed to sidJ diversification. Additionally, we showed that four codons of sidJ which are located in the N-terminal (NTD) (codons 58 and 200) and C-terminal (CTD) (codons 868 and 869) domains, but not in the kinase domain (KD) had been subjected to strong positive selection pressure, and variable mutation profiles of these codons were identified. Protein structural modeling of SidJ provided possible explanations for these mutations. Codons 868 and 869 mutations might engage in regulating the interactions of SidJ with CaM through hydrogen bonds and affect the CaM docking to SidJ. Mutation in codon 58 of SidJ might affect the distribution of main-chain atoms that are associated with the interaction with CaM. In contrast, mutations in codon 200 might influence the α-helix stability in the NTD. These mutations might be important to balance Ub ligase activity for different L. pneumophila hosts. This study first reported that intragenic recombination and positive Darwinian selection both shaped the genetic plasticity of sidJ, contributing to a deeper understanding of the adaptive mechanisms of this intracellular bacterium to different hosts.
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Project description:BackgroundPE and PE_PGRS are two mycobateria-restricted multigene families encoding membrane associated and secreted proteins that have expanded mainly in the pathogenic species, notably the Mycobacterium tuberculosis complex (MTBC). Several lines of evidence attribute to PE and PE_PGRS genes critical roles in mycobacterial pathogenicity. To get more insight into the nature of these genes, we sought to address their evolutionary trajectories in the group of smooth tubercle bacilli (STB), the putative ancestor of the clonal MTBC.Methodology/principal findingsBy focussing on six polymorphic STB PE/PE_PGRS genes, we demonstrate significant incongruence among single gene genealogies and detect strong signals of recombination using various approaches. Coalescent-based estimation of population recombination and mutation rates (ρ and θ, respectively) indicates that the two mechanisms are of roughly equal importance in generating diversity (ρ/θ = 1.457), a finding in a marked contrast to house keeping genes (HKG) whose evolution is chiefly brought about by mutation (ρ/θ = 0.012). In comparison to HKG, we found 15 times higher mean rate of nonsynonymous substitutions, with strong evidence of positive selection acting on PE_PGRS62 (dN/dS = 1.42), a gene that has previously been shown to be essential for mycobacterial survival in macrophages and granulomas. Imprint of positive selection operating on specific amino acid residues or along branches of PE_PGRS62 phylogenetic tree was further demonstrated using maximum likelihood- and covarion-based approaches, respectively. Strikingly, PE_PGR62 proved highly conserved in present-day MTBC strains.Conclusions/significanceOverall the data indicate that, in STB, PE/PE_PGRS genes have undergone a strong diversification process that is speeded up by recombination, with evidence of positive selection. The finding that positive selection involved an essential PE_PGRS gene whose sequence appears to be driven to fixation in present-day MTBC strains lends further support to the critical role of PE/PE_PGRS genes in the evolution of mycobacterial pathogenicity.
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Project description:Studies of protein fitness landscapes reveal biophysical constraints guiding protein evolution and empower prediction of functional proteins. However, generalisation of these findings is limited due to scarceness of systematic data on fitness landscapes of proteins with a defined evolutionary relationship. We characterized the fitness peaks of four orthologous fluorescent proteins with a broad range of sequence divergence. While two of the four studied fitness peaks were sharp, the other two were considerably flatter, being almost entirely free of epistatic interactions. Mutationally robust proteins, characterized by a flat fitness peak, were not optimal templates for machine-learning-driven protein design - instead, predictions were more accurate for fragile proteins with epistatic landscapes. Our work paves insights for practical application of fitness landscape heterogeneity in protein engineering.
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Project description:Meiotic recombination is believed to produce greater genetic variation despite the fact that deoxyribonucleic acid (DNA)-replication errors are a major source of mutations. In some vertebrates, mutation rates are higher in males than in females, which developed the theory of male-driven evolution (male-biased mutation). However, there is little molecular evidence regarding the relationships between meiotic recombination and male-biased mutation. Here we tested the theory using the frog Rana rugosa, which has both XX/XY- and ZZ/ZW-type sex-determining systems within the species. The male-to-female mutation-rate ratio (?) was calculated from homologous sequences on the X/Y or Z/W sex chromosomes, which supported male-driven evolution. Surprisingly, each ? value was notably higher in the XX/XY-type group than in the ZZ/ZW-type group, although ? should have similar values within a species. Interestingly, meiotic recombination between homologous chromosomes did not occur except at terminal regions in males of this species. Then, by subdividing ? into two new factors, a replication-based male-to-female mutation-rate ratio (?) and a meiotic recombination-based XX-to-XY/ZZ-to-ZW mutation-rate ratio (?), we constructed a formula describing the relationship among a nucleotide-substitution rate and the two factors, ? and ?. Intriguingly, the ?- and ?-values were larger and smaller than 1, respectively, indicating that meiotic recombination might reduce male-biased mutations.
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Project description:Recombination has the potential to facilitate adaptation. In spite of the substantial body of theory on the impact of recombination on the evolutionary dynamics of adapting populations, empirical evidence to test these theories is still scarce. We examined the effect of recombination on adaptation on a large-scale empirical fitness landscape in HIV-1 based on in vitro fitness measurements. Our results indicate that recombination substantially increases the rate of adaptation under a wide range of parameter values for population size, mutation rate and recombination rate. The accelerating effect of recombination is stronger for intermediate mutation rates but increases in a monotonic way with the recombination rates and population sizes that we examined. We also found that both fitness effects of individual mutations and epistatic fitness interactions cause recombination to accelerate adaptation. The estimated epistasis in the adapting populations is significantly negative. Our results highlight the importance of recombination in the evolution of HIV-I.
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