Host–Parasite Interactions and the Evolution of Gene Expression

Interactions between hosts and parasites provide an ongoing source of selection that promotes the evolution of a variety of features in the interacting species. Here, we use a genetically explicit mathematical model to explore how patterns of gene expression evolve at genetic loci responsible for host resistance and parasite infection. Our results reveal the striking yet intuitive conclusion that gene expression should evolve along very different trajectories in the two interacting species. Specifically, host resistance loci should frequently evolve to co-express alleles, whereas parasite infection loci should evolve to express only a single allele. This result arises because hosts that co-express resistance alleles are able to recognize and clear a greater diversity of parasite genotypes. By the same token, parasites that co-express antigen or elicitor alleles are more likely to be recognized and cleared by the host, and this favours the expression of only a single allele. Our model provides testable predictions that can help interpret accumulating data on expression levels for genes relevant to host−parasite interactions

Can Double PPO Mutations Exist in the Same Allele and are Such Mutants Functional?

BACKGROUND Resistance to protoporphyrinogen oxidase (PPO)-inhibiting herbicides is endowed primarily by target-site mutations at the PPX2 gene that compromise binding of the herbicide to the catalytic domain. In Amaranthus spp. PPX2, the most prevalent target mutations are deletion of the G210 codon, and the R128G and G339A substitutions. These mutations strongly affect the dynamic of the PPO2 binding pocket, resulting in reduced affinity with the ligand. Here we investigated the likelihood of co-occurrence of the most widespread target site mutations in the same PPX2 allele. RESULTS Plants carrying R128G+/+ ΔG210+/−, where + indicates presence of the mutation, were crossed with each other. The PPX2 of the offspring was subjected to pyrosequencing and E. coli-based Sanger sequencing to determine mutation frequencies and allele co-occurrence. The data show that R128G ΔG210 can occur in one allele only; the second allele carries only one mutation. Double mutation in both alleles is less likely because of significant loss of enzyme activity. The segregation of offspring populations derived from a cross between heterozygous plants carrying ΔG210 G399A also showed no co-occurrence in the same allele. The offspring exhibited the expected mutation distribution patterns with few exceptions. CONCLUSIONS Homozygous double-mutants are not physiologically viable. Double-mutant plants can only exist in a heterozygous state. Alternatively, if two mutations are detected in one plant, each mutation would occur in a separate allele

The Soybean \u3cem\u3eRfg1\u3c/em\u3e Gene Restricts Nodulation by \u3cem\u3eSinorhizobium fredii\u3c/em\u3e USDA193

Sinorhizobium fredii is a fast-growing rhizobial species that can establish a nitrogen-fixing symbiosis with a wide range of legume species including soybeans (Glycine max). In soybeans, this interaction shows a high level of specificity such that particular S. fredii strains nodulate only a limited set of plant genotypes. Here we report the identification of a dominant gene in soybeans that restricts nodulation with S. fredii USDA193. Genetic mapping in an F2 population revealed co-segregation of the underlying locus with the previously cloned Rfg1 gene. The Rfg1 allele encodes a member of the Toll-interleukin receptor/nucleotide-binding site/leucine-rich repeat class of plant resistance proteins that restricts nodulation by S. fredii strains USDA257 and USDA205, and an allelic variant of this gene also restricts nodulation by Bradyrhizobium japonicum USDA122. By means of complementation tests and CRISPR/Cas9-mediated gene knockouts, we demonstrate that the Rfg1 allele also is responsible for resistance to nodulation by S. fredii USDA193. Therefore, the Rfg1 allele likely provides broad-spectrum resistance to nodulation by many S. fredii and B. japonicum strains in soybeans

Machine learning and structural analysis of Mycobacterium tuberculosis pan-genome identifies genetic signatures of antibiotic resistance.

Mycobacterium tuberculosis is a serious human pathogen threat exhibiting complex evolution of antimicrobial resistance (AMR). Accordingly, the many publicly available datasets describing its AMR characteristics demand disparate data-type analyses. Here, we develop a reference strain-agnostic computational platform that uses machine learning approaches, complemented by both genetic interaction analysis and 3D structural mutation-mapping, to identify signatures of AMR evolution to 13 antibiotics. This platform is applied to 1595 sequenced strains to yield four key results. First, a pan-genome analysis shows that M. tuberculosis is highly conserved with sequenced variation concentrated in PE/PPE/PGRS genes. Second, the platform corroborates 33 genes known to confer resistance and identifies 24 new genetic signatures of AMR. Third, 97 epistatic interactions across 10 resistance classes are revealed. Fourth, detailed structural analysis of these genes yields mechanistic bases for their selection. The platform can be used to study other human pathogens

Gombarezisztencia gének térképezése szőlőben = Mapping resistance genes against fungi in grapevine

Lisztharmat (PM) és peronoszpóra (DM) rezisztencia génekkel kapcsolt markerek szelekcióra való alkalmasságát vizsgáltuk szőlő inter-és intraspecifikus térképezési populációiban. Az interspecifikus hibridek a Muscadina rotundifolia x Vitis vinfera BC4 Cardinal, Kismis moldavszkij és Kismis vatkana fajtákkal előállított BC5 nemzedékei voltak. A M. rotundifolia az ismert RUN1 (PM) és az RPV1 (DM) domináns rezisztencia géneket tartalmazza. A BC5 nemzedékekben 1 CAPS és 3 SSR markerrel hatékonyan szelektáltuk a rezisztens genotípusokat. A V. vinifera fajták általában fogékonyak a lisztharmatra, de a fogékonyságuk eltérő. A Dzsandzsal karát írták le először PM rezisztens fajtaként, később azonban többet is azonosítottak, köztük a Kismis vatkanát, rezisztencia génjüket azonban nem jellemezték. A Nimrang x Kismis vatkana hibrid család elemzése során bebizonyosodott, hogy a Kismis vatkana PM génje, amelyet REN1-nek neveztek el, nem azonos a RUN1-gyel. A 13-as kromoszómára térképeződött, míg a RUN1 a 12-re. A REN1 körül azonosított 3 SSR markerrel genotipizáltuk a Génuai zamatos x Kismis vatkana és BC4 x Kismis vatkana utódokat. Az utóbbi család egyedei közül RUN1/REN1 piramidált genotípusokat szelektáltunk. Az azonos fenotípust meghatározó piramidált géneket tartalmazó növények azonosítása csak DNS-szintű elemzéssel lehetséges. A MAS hatékonyságának növelésére multiplex PCR módszert dolgoztunk ki. A REN1-gyel kapcsolt marker SSR profil alapján a Dzsandzsal kara is REN1 gént hordoz. | For validating markers linked to powdery (PM) and downy (DM) mildew resistance genes, applying them in marker assisted selection (MAS) we analyzed mapping populations, deriving from interspecific crosses of Vitis vinifera with Muscadinia rotundifolia carrying the dominant RUN1 (PM) and RPV1 (DM) resistance genes. One CAPS and 3 SSR markers proved to be adequate for selecting RUN1/RPV1 genotypes in the (M. rotundifolia x V. vinifera) BC4 x Cardinal, BC4 x Kishmish moldavskij and BC4 x Kishmish vatkana families. Kishmish vatkana is a PM resistant V. vinifera cultivar such as Dzhandzhal kara. Involving V. vinifera resistance genes into breeding gives the chance to avoid interspecific crosses. Analysis of a Nimrang x Kishmis vatkana progeny proved that PM resistance gene of Kishmish vatkana, called REN1, is different from RUN1. REN1 mapped into linkage group/LG 13, while RUN1 is in LG12. Three SSR markers were identified around the REN1 locus and applied for MAS in Génuai zamatos x Kishmis vatkana and BC4 x Kishmish vatkana hybrids. In this latter cross we proved the presence of the pyramided PM resistance genes. Plants carrying both RUN1 and REN1 for the same phenotype can be identified only with DNA analysis. This is the first time when SSR markers linked to REN1 were used for MAS. We elaborated a multiplex PCR method suitable for agarose electrophoresis. SSR profiles in REN1 linked loci suggest that Kismish vatkana and Dzhandzhal kara possess the same REN1 PM resistance gene

Geographical distribution of selected and putatively neutral SNPs in Southeast Asian malaria parasites.

Loci targeted by directional selection are expected to show elevated geographical population structure relative to neutral loci, and a flurry of recent papers have used this rationale to search for genome regions involved in adaptation. Studies of functional mutations that are known to be under selection are particularly useful for assessing the utility of this approach. Antimalarial drug treatment regimes vary considerably between countries in Southeast Asia selecting for local adaptation at parasite loci underlying resistance. We compared the population structure revealed by 10 nonsynonymous mutations (nonsynonymous single-nucleotide polymorphisms [nsSNPs]) in four loci that are known to be involved in antimalarial drug resistance, with patterns revealed by 10 synonymous mutations (synonymous single-nucleotide polymorphisms [sSNPs]) in housekeeping genes or genes of unknown function in 755 Plasmodium falciparum infections collected from 13 populations in six Southeast Asian countries. Allele frequencies at known nsSNPs underlying resistance varied markedly between locations (F(ST) = 0.18-0.66), with the highest frequencies on the Thailand-Burma border and the lowest frequencies in neighboring Lao PDR. In contrast, we found weak but significant geographic structure (F(ST) = 0-0.14) for 8 of 10 sSNPs. Importantly, all 10 nsSNPs showed significantly higher F(ST) (P < 8 x 10(-5)) than simulated neutral expectations based on observed F(ST) values in the putatively neutral sSNPs. This result was unaffected by the methods used to estimate allele frequencies or the number of populations used in the simulations. Given that dense single-nucleotide polymorphism (SNP) maps and rapid SNP assay methods are now available for P. falciparum, comparing genetic differentiation across the genome may provide a valuable aid to identifying parasite loci underlying local adaptation to drug treatment regimes or other selective forces. However, the high proportion of polymorphic sites that appear to be under balancing selection (or linked to selected sites) in the P. falciparum genome violates the central assumption that selected sites are rare, which complicates identification of outlier loci, and suggests that caution is needed when using this approach

Analysis of putative resistance gene loci in UK field populations of Haemonchus contortus after six years of macrocyclic lactone use

Sheep farmers in the UK rely on strategic anthelmintic use to treat and control gastrointestinal roundworms in their flocks. However, resistance to these drugs is now widespread and threatens the sustainability of sheep production. The mechanisms underlying resistance to the most commonly used class, the macrocyclic lactones, are not known and sensitive diagnostic tools based on molecular markers are not currently available. This prohibits accurate surveillance of resistance or assessment of strategies aimed at controlling its spread. In this study, we examined four UK field populations of Haemonchus contortus, differing in macrocyclic lactone treatment history, for evidence of selection at ‘candidate gene’ loci identified as determining macrocyclic lactone resistance in previously published research. Individual worms were genotyped at Hc-lgc-37, Hc-glc-5, Hc-avr-14 and Hc-dyf-7, and four microsatellite loci. High levels of polymorphism were identified at the first three candidate gene loci with remarkably little polymorphism at Hc-dyf-7. While some between-population comparisons of individual farms with and without long-term macrocyclic lactone use identified statistically significant differences in allele frequency and/or fixation index at the Hc-lgc-37, Hc-glc-5 or Hc-avr-14 loci, we found no consistent evidence of selection in other equivalent comparisons. While it is possible that different mechanisms are important in different populations or that resistance may be conferred by small changes at multiple loci, our findings suggest that these are unlikely to be major loci conferring macrocyclic lactone resistance on UK farms or suitable for diagnostic marker development. More powerful approaches, using genome-wide or whole genome sequencing, may be required to define macrocyclic lactone resistance loci in such genetically variable populations

Pyramiding of Ryd2 and Ryd3 conferring tolerance to a German isolate of Barley yellow dwarf virus-PAV (BYDV-PAV-ASL-1) leads to quantitative resistance against this isolate

Barley yellow dwarf virus (BYDV) is an economically important pathogen of barley, which may become even more important due to global warming. In barley, several loci conferring tolerance to BYDV-PAV-ASL-1 are known, e.g. Ryd2, Ryd3 and a quantitative trait locus (QTL) on chromosome 2H. The aim of the present study was to get information whether the level of tolerance against this isolate of BYDV in barley can be improved by combining these loci. Therefore, a winter and a spring barley population of doubled haploid (DH) lines were genotyped by molecular markers for the presence of the susceptibility or the resistance encoding allele at respective loci (Ryd2, Ryd3, QTL on chromosome 2H) and were tested for their level of BYDV-tolerance after inoculation with viruliferous (BYDV-PAV-ASL-1) aphids in field trials. In DH-lines carrying the combination Ryd2 and Ryd3, a significant reduction of the virus titre was detected as compared to lines carrying only one of these genes. Furthermore, spring barley DH-lines with this allele combination also showed a significantly higher relative grain yield as compared to lines carrying only Ryd2 or Ryd3. The QTL on chromosome 2H had only a small effect on the level of tolerance in those lines carrying only Ryd2, or Ryd3 or a combination of both, but the effect in comparison to lines carrying no tolerance allele was significant. Overall, these results show that the combination of Ryd2 and Ryd3 leads to quantitative resistance against BYDV-PAV instead of tolerance