Conflicts with diarrheal pathogens trigger rapid evolution of an intestinal signaling axis
Posted on: 17 April 2020
Preprint posted on 30 March 2020
Article now published in Cell Host & Microbe at http://dx.doi.org/10.1016/j.chom.2021.07.005
Categories: biochemistry, evolutionary biology, microbiology
Background:
Pathogens represent a danger for all organisms necessitating the evolution of molecular defenses, from bacterial immune systems such as CRISPR and restriction enzymes to the evolution of adaptive immune systems in vertebrate animals. Beyond the development of specialized immune systems, the effect of pathogens on particular biological processes can be identified from genomic signatures. The co-evolution of pathogens with particular host proteins can be tracked with evidence of adaptive evolution and natural selection. In particular, the more rapid change in proteins targeted by particular pathogens, often measured by the ratio dN/dS (the ratio of non-synonymous to synonymous nucleotide changes between homologous proteins across species), is strong evidence of an evolutionary pressure from the pathogen. The back-and-forth evolution of pathogens to target the host, the host mutating to avoid or neutralize pathogen activity, and subsequent re-adaptation of the pathogen can result in an “arms-race” dynamic. While individual investigations have revealed signatures of host-pathogen co-evolution and “arms-races” in a number of immune proteins [Daugherty and Malik, 2012], the extent of the evolutionary pressures that pathogens represent on a broader range of physiological pathways has remained unclear. In this preprint, Carey et al identify signatures of rapid evolution at mammalian Guanylate Cyclase-C (GC-C), a regulator of intestinal osmotic balance, that appear to be driven by pressures from pathogen-derived toxins.
Key findings:
- Rapid evolution in GC-C and response to bacterial enterotoxins
GC-C is targeted by diarrhea-inducing enterotoxins from multiple pathogens. Primate GC-C sequences showed evidence of positive selection in the extracellular region, where toxins bind, and divergent binding towards enterotoxins derived from different pathogens. Among other mammalian lineages, bats showed extremely widespread positive selection in GC-C, again located exclusively in the extracellular region, and divergent susceptibility towards toxins from particular pathogens. These data suggest that the evasion of pathogen toxins is a sufficient evolutionary pressure to drive adaptive evolution in the toxin target, a regulator of a basic physiological process.
- Co-evolution of uroguanylin with GC-C in bats
The rapid evolution of GC-C in bats raises an evolutionary conundrum – GC-C responds to endogenous ligands (guanylin and uroguanylin) in order to carry out the basic function of intestinal water regulation. Uroguanylin sequences in bats show more variability across species than primates, consistent with the increased burden of GC-C mutations. Uroguanylin peptides showed species-specificity in their activating potential towards bat GC-C receptors, suggesting co-evolution to maintain binding in the presence of the “third party” pressure from the toxins. Interestingly, one species of bat showed reduced activity towards all uroguanylin peptides, including its own, suggesting it exists in an evolutionary “intermediate state” where it has decreased sensitivity to both toxins and uroguanylin.
Importance:
This preprint presents strong evidence for the pathogen-driven evolution of GC-C in primates and bats, and the co-evolution of uroguanylin in bats. This shows the immense selective pressure individual pathogens can exert on a broad range of pathways in host physiology – driving evolution not only of classical “immune” genes, but demonstrating that bacterial enterotoxins are sufficient to shape basic intestinal physiology over evolutionary timescales. Additionally, this study reveals the rapid evolution of bats in response to bacterial pathogens, including the ability to partially “neglect” basic GC-C regulation. This is of particular interest given that the range of unique adaptations in bat antiviral immunity may factor into their role as reservoirs of zoonotic viruses (Xie et al 2018, Ahn et al 2019, Lu and Liu et al 2019 as non-exhaustive recent examples), and raises the question of whether they might harbor similar reservoirs of zoonotic bacteria.
Moving Forward / Questions for Authors:
- Why might bats be so sensitive to diarrheal pathogens? The strong evidence of positive selection contrasts with a lack of positive selection in other lineages with evidence of bacterial enterotoxins, such as Bovidae. One obvious difference is a flying lifestyle, but are there other aspects of bat physiology that might explain the need to evolve so rapidly as to reach those “intermediate states” of impaired endogenous uroguanylin sensitivity?
- Are the patterns of evolution and toxin evasion sufficient to guess at the original selective pressures driving differences in bats? For example, it appears that the major difference between lucifugus and P. vampyrus is in sensitivity to Yersinia enterotoxin, with minor differences in sensitivity to the other toxins. How would the authors predict this would occur from, for example, a single plague outbreak leading to a bottlenecking event in an ancestor of P. vampyrus, versus geographic isolation and differential pathogen exposure leading to gradual selection during speciation?
References:
- Ahn M et al, “Dampened NLRP3-mediated inflammation in bats and implications for a special viral reservoir host”, Nature Microbiology (2019) 4:789-799
- Daugherty MD and Malik HS, “Rules of Engagement: Molecular Insights from Host-Virus Arms Races”, Annual Reviews of Genetics (2012) 46:677-700
- Lu D and Liu K et al, “Peptide presentation by bat MHC class I provides new insight into the antiviral immunity of bats”, PLOS Biology (2019) doi:10.1371/journal.pbio.3000436
- Xie J et al, “Dampened STING-Dependent Interferon Activation in Bats”, Cell Host and Microbe (2018) 23:297-301
doi: https://doi.org/10.1242/prelights.18822
Read preprint
(No Ratings Yet)Sign up to customise the site to your preferences and to receive alerts
Register hereAlso in the biochemistry category:
Triglyceride metabolism controls inflammation and APOE4-associated disease states in microglia
Gustavo Stelzer, Marcus Oliveira
Impaired 26S proteasome causes learning and memory deficiency and induces neuroinflammation mediated by NF-κB in mice
Gustavo Stelzer, Marcus Oliveira
Notch3 is a genetic modifier of NODAL signalling for patterning asymmetry during mouse heart looping
Bhaval Parmar
Also in the evolutionary biology category:
Enhancer-driven cell type comparison reveals similarities between the mammalian and bird pallium
Rodrigo Senovilla-Ganzo
Modular control of time and space during vertebrate axis segmentation
AND
Natural genetic variation quantitatively regulates heart rate and dimension
Girish Kale, Jennifer Ann Black
Fetal brain response to maternal inflammation requires microglia
Manuel Lessi
Also in the microbiology category:
Significantly reduced, but balanced, rates of mitochondrial fission and fusion are sufficient to maintain the integrity of yeast mitochondrial DNA
Leeba Ann Chacko
The bat Influenza A virus subtype H18N11 induces nanoscale MHCII clustering upon host cell attachment
Mitchell Sarmie, Mohammed A. Jalloh
Characterization of natural product inhibitors of quorum sensing in Pseudomonas aeruginosa reveals competitive inhibition of RhlR by ortho-vanillin
UofA IMB565 et al.
preLists in the biochemistry category:
BSCB-Biochemical Society 2024 Cell Migration meeting
This preList features preprints that were discussed and presented during the BSCB-Biochemical Society 2024 Cell Migration meeting in Birmingham, UK in April 2024. Kindly put together by Sara Morais da Silva, Reviews Editor at Journal of Cell Science.
| List by | Reinier Prosee |
Peer Review in Biomedical Sciences
Communication of scientific knowledge has changed dramatically in recent decades and the public perception of scientific discoveries depends on the peer review process of articles published in scientific journals. Preprints are key vehicles for the dissemination of scientific discoveries, but they are still not properly recognized by the scientific community since peer review is very limited. On the other hand, peer review is very heterogeneous and a fundamental aspect to improve it is to train young scientists on how to think critically and how to evaluate scientific knowledge in a professional way. Thus, this course aims to: i) train students on how to perform peer review of scientific manuscripts in a professional manner; ii) develop students' critical thinking; iii) contribute to the appreciation of preprints as important vehicles for the dissemination of scientific knowledge without restrictions; iv) contribute to the development of students' curricula, as their opinions will be published and indexed on the preLights platform. The evaluations will be based on qualitative analyses of the oral presentations of preprints in the field of biomedical sciences deposited in the bioRxiv server, of the critical reports written by the students, as well as of the participation of the students during the preprints discussions.
| List by | Marcus Oliveira et al. |
CellBio 2022 – An ASCB/EMBO Meeting
This preLists features preprints that were discussed and presented during the CellBio 2022 meeting in Washington, DC in December 2022.
| List by | Nadja Hümpfer et al. |
20th “Genetics Workshops in Hungary”, Szeged (25th, September)
In this annual conference, Hungarian geneticists, biochemists and biotechnologists presented their works. Link: http://group.szbk.u-szeged.hu/minikonf/archive/prg2021.pdf
| List by | Nándor Lipták |
Fibroblasts
The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!
| List by | Osvaldo Contreras |
ASCB EMBO Annual Meeting 2019
A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)
| List by | Madhuja Samaddar et al. |
EMBL Seeing is Believing – Imaging the Molecular Processes of Life
Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019
| List by | Dey Lab |
Cellular metabolism
A curated list of preprints related to cellular metabolism at Biorxiv by Pablo Ranea Robles from the Prelights community. Special interest on lipid metabolism, peroxisomes and mitochondria.
| List by | Pablo Ranea Robles |
MitoList
This list of preprints is focused on work expanding our knowledge on mitochondria in any organism, tissue or cell type, from the normal biology to the pathology.
| List by | Sandra Franco Iborra |
Also in the evolutionary biology category:
‘In preprints’ from Development 2022-2023
A list of the preprints featured in Development's 'In preprints' articles between 2022-2023
| List by | Alex Eve, Katherine Brown |
preLights peer support – preprints of interest
This is a preprint repository to organise the preprints and preLights covered through the 'preLights peer support' initiative.
| List by | preLights peer support |
EMBO | EMBL Symposium: The organism and its environment
This preList contains preprints discussed during the 'EMBO | EMBL Symposium: The organism and its environment', organised at EMBL Heidelberg, Germany (May 2023).
| List by | Girish Kale |
9th International Symposium on the Biology of Vertebrate Sex Determination
This preList contains preprints discussed during the 9th International Symposium on the Biology of Vertebrate Sex Determination. This conference was held in Kona, Hawaii from April 17th to 21st 2023.
| List by | Martin Estermann |
EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)
A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.
| List by | Alex Eve |
Planar Cell Polarity – PCP
This preList contains preprints about the latest findings on Planar Cell Polarity (PCP) in various model organisms at the molecular, cellular and tissue levels.
| List by | Ana Dorrego-Rivas |
TAGC 2020
Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20
| List by | Maiko Kitaoka et al. |
ECFG15 – Fungal biology
Preprints presented at 15th European Conference on Fungal Genetics 17-20 February 2020 Rome
| List by | Hiral Shah |
COVID-19 / SARS-CoV-2 preprints
List of important preprints dealing with the ongoing coronavirus outbreak. See http://covidpreprints.com for additional resources and timeline, and https://connect.biorxiv.org/relate/content/181 for full list of bioRxiv and medRxiv preprints on this topic
| List by | Dey Lab, Zhang-He Goh |
1
SDB 78th Annual Meeting 2019
A curation of the preprints presented at the SDB meeting in Boston, July 26-30 2019. The preList will be updated throughout the duration of the meeting.
| List by | Alex Eve |
Pattern formation during development
The aim of this preList is to integrate results about the mechanisms that govern patterning during development, from genes implicated in the processes to theoritical models of pattern formation in nature.
| List by | Alexa Sadier |
Also in the microbiology category:
BioMalPar XVI: Biology and Pathology of the Malaria Parasite
[under construction] Preprints presented at the (fully virtual) EMBL BioMalPar XVI, 17-18 May 2020 #emblmalaria
| List by | Dey Lab, Samantha Seah |
1
ECFG15 – Fungal biology
Preprints presented at 15th European Conference on Fungal Genetics 17-20 February 2020 Rome
| List by | Hiral Shah |
EMBL Seeing is Believing – Imaging the Molecular Processes of Life
Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019
| List by | Dey Lab |
Antimicrobials: Discovery, clinical use, and development of resistance
Preprints that describe the discovery of new antimicrobials and any improvements made regarding their clinical use. Includes preprints that detail the factors affecting antimicrobial selection and the development of antimicrobial resistance.
| List by | Zhang-He Goh |