bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2024.08.15.607931

Genetic basis of resistance in hosts facing alternative infection strategies by a virulent bacterial pathogen

Mathieu-Begne, E.·Gattis, S.·Ebert, D.
View original source ↗Export metadata ↓

Abstract

Having alternative infection routes is thought to help parasites circumvent host resistance, provided that these routes are associated with different host resistance loci. This study examines whether alternate infection routes of the parasite Pasteuria ramosa are linked to distinct resistance loci in its crustacean host, Daphnia magna. We focus on the P. ramosa isolate P15, which can attach and penetrate the host through either the hindgut or the foregut. Using a global panel of 174 D. magna genotypes supplemented with breeding experiments, we analyzed resistance patterns for each of these infection routes. Our findings confirm our hypothesis: in D. magna, hindgut attachment is determined by the D locus, while foregut attachment is controlled by a newly identified G locus. We established a gene model for the G locus that indicated Mendelian segregation and epistatic interaction with at least one other resistance locus for P. ramosa, the C locus. Using genomic Pool-sequencing data, we localized the G locus within a known Pasteuria Resistance Complex on chromosome 4 of D. magna, whereas the D locus is on chromosome 7. Two candidate genes for the G locus, belonging to the Glycosyltransferase gene family, were identified. Our study sheds new light on host-parasite coevolution and enhances our understanding of how parasites evolve infection strategies. Author summaryParasites continuously evolve strategies to overcome host resistance, including the use of alternative infection routes. However, this strategy is advantageous only if host resistance loci are specific to each entry point; otherwise, a single host gene could provide resistance to all infection routes. In this study, we tested this hypothesis using the freshwater crustacean Daphnia magna and a strain of the parasite Pasteuria ramosa that can infect its host via the esophagus (foregut) or the hindgut. By conducting a phenotypic assay of P. ramosa attachment on a global panel of D. magna genotypes, we demonstrate that foregut and hindgut infections are associated with independent genetic host resistance loci. Through a breeding experiment on a subset of D. magna genotypes, we were able to propose a gene model for the newly discovered G locus linked to foregut attachment, while the previously identified D locus is linked to hindgut attachment. We also discovered that the foregut infection route is influenced by an epistatic interaction between the G locus and another P. ramosa resistance locus, the C locus. Using genomic data, we confirmed that the G and D loci are not overlapping, with the G locus being part of the Pasteuria Resistance Complex on chromosome 4, whereas the D locus is on chromosome 7. Two potential genes involved in glycosylation processes were identified as candidates for the G locus. Overall, our study confirms a key postulate in the understanding of host-parasite co-evolution, highlighting the importance of infection strategies in host resistance.

Source connections

Explore related subjects

evolutionary biologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Mathieu-Begne, E., Gattis, S., Ebert, D.. 2024-08-17. Genetic basis of resistance in hosts facing alternative infection strategies by a virulent bacterial pathogen. https://doi.org/10.1101/2024.08.15.607931

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Denisovan introgression left differential selection regimes in Humans and Neanderthals on the SLC30A9 gene

Signals of positive selection around the SLC30A9 gene have been reported in human populations outside Africa. Selection likely acted on a highly differentiated single-nucleotide polymorphism, rs1047626, leading to a non-synonymous substitution in the encoded zinc transporter. Because of the striking similarity between the putatively selected SLC30A9 haplotype observed in several current human populations and the Denisovan individual, previous work has proposed adaptive introgression. Yet alternative explanations, including ancient human variation, and the precise archaic source -Neanderthal or Denisovan- remained unresolved. Considering the potentially complex evolution of SLC30A9, we applied Approximate Bayesian Computation (ABC) algorithms coupled to machine learning to investigate the most plausible evolutionary origin of this substitution. After modelling different evolutionary scenarios with forward-in-time simulations, our results highlight that the most probable scenario is a Denisovan origin of the rs1047626 polymorphism. However, the allele likely introgressed into Neanderthals first and was then passed into non-African modern humans. Moreover, the derived allele frequency for rs1047626 across several African populations is consistent with back-to-Africa migrations. Finally, our ABC analyses indicate strong positive selection in East Asian populations and other out-of-Africa populations, whereas in Neanderthal populations, the selection coefficient was probably neutral or slightly deleterious.

evolutionary biology↗
bioRxiv2026

RELAX does not reproduce its own estimates at default settings, and its output does not show it

Selection-intensity estimates from RELAX are reported as a point value of K with a likelihood-ratio P. We report that, at default settings and on data of ordinary size, the program does not reproduce its own fits. Of 27 enzyme entries refitted under two optimiser configurations, none reproduced its log-likelihood to within 0.01 units; the median change was 103 units, the largest over 3,400, and four verdicts reversed. Eighty null orthologues reproduced none. A byte-identical command returned a distinct likelihood on every repetition, single-threaded, across three releases, and on alignments simulated under the fitted model, where 3.3 per cent of replicates reproduced. The documented random-number seed never reaches the generator when assigned on the command line, yet reads back as the value supplied. PAML localises the cause: its two-ratio model, without site classes, reproduced its log-likelihood for all 288 genes; its site-class models agreed for 27 to 67 per cent. The instability follows the mixture over sites, not the program. The output does not show it: 46 of 410 fits ended with a negative likelihood-ratio statistic, impossible under convergence, and 123 of 410 report a K re-estimated under a domain restriction rather than the unconstrained maximum. Of 234 published studies using RELAX, none reported a seed. Seeding while holding the thread count at one reproduced sixty of sixty runs on twenty genes under two releases; the seed alone reproduced none of five, and no documentation states the second condition. We recommend that fits be repeated and their dispersion published.

evolutionary biology↗
bioRxiv2026

Sequential accumulation of adaptive alleles forms an inversion supergene in deer mice

Supergenes are clusters of co-inherited loci that affect multiple or complex phenotypes. Despite the growing number of chromosomal inversions identified as supergenes in natural populations, their molecular basis and evolutionary history often remain obscure. Here, we identified two candidate genes, Slc45a2 and Npr3, within a 41-Mb inversion supergene in the deer mouse (Peromyscus maniculatus) that respectively drive darker coats and longer tails - two traits associated with forest adaptation. Mice homozygous for the inversion (inv/inv) exhibit elevated Slc45a2 expression in melanocytes relative to the congenic standard genotype (std/std), disrupting pheomelanin production. In parallel, downregulation of Npr3 in inv/inv mouse growth plates prolongs postnatal growth of caudal vertebrae, resulting in tail elongation. Population-level analyses further implicate that this supergene arose through the subsequent accumulation of the Npr3 allele within the inversion, rather than by capturing all beneficial mutations at its origin.

evolutionary biology↗