Close
Close

preLights is supported by…

Related posts

Related preLists

Conflicts with diarrheal pathogens trigger rapid evolution of an intestinal signaling axis

Clayton M. Carey, Sarah E. Apple, Zoё A. Hilbert, Michael S. Kay, Nels C. Elde

Preprint posted on 30 March 2020 https://www.biorxiv.org/content/10.1101/2020.03.29.014761v1

Article now published in Cell Host & Microbe at http://dx.doi.org/10.1016/j.chom.2021.07.005

Conflicts in the Gut – Diarrheal Pathogens Driving Host Evolution

Selected by Connor Rosen

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

 

Posted on: 17 April 2020

doi: https://doi.org/10.1242/prelights.18822

Read preprint (No Ratings Yet)

Author's response

Clay Carey shared

Hello, this is Clay Carey. I am the first author of the study highlighted here. Thank you for your great write-up, I am grateful for your interest in our work!

We observed very striking levels of divergence in GC-C among bats and substitution patterns consistent with strong selective pressure to modulate toxin interactions. Why bats might be subject to such intense selection relative to other mammals is an interesting question. As you noted, they have the unique ability of flight among mammals, which allows them to cover large geographic distances, providing more opportunities to encounter pathogens. What I think is probably a more important lifestyle factor is that all the bat species we sampled in our study live in high-density colonies with thousands or even millions of individuals sharing confined spaces and communal resources. We know conditions like these are conducive to the spread of diarrheal diseases in humans. It would be interesting to know whether these evolutionary patterns are different in bat species that live a more solitary lifestyle. An additional factor to consider is a heightened metabolic rate in bats might make water an even more precious resource, so losing the ability to fine tune water secretion via uroguanylin signaling might be more tolerable. I hope that our work can spark more interest in these hypotheses and the community can begin to experimentally test the links between host behavior and physiology and susceptibility to diarrheal disease.

We did find significant differences in susceptibility to toxin from Yersinia enterocolitica between different bat species, to the point where the giant fruit bat Pteropus vampyrus seems to be nearly immune to the effects of the toxin compared to the more susceptible vesper bat Myotis lucifugus. While it is tempting to speculate that there was a bottleneck event during an outbreak of Yersinia enterocolitica in an ancestor of the modern old world fruit bats that resulted in fixation of a resistant allele, we really can’t know if that is the case. Given the evidence of intense selection in GC-C even in the deep branches of the chiropteran tree, it is likely that bats have encountered many different STa-like peptides over the course of millions of years of evolution. One thing to consider is that our study has an anthropocentric bias in terms of the toxins we tested. This is out of necessity, because we only really know about the toxin variants found in human pathogens! I think we have only scratched the surface in terms of bacterial diversity of these heat-stable enterotoxins that target GC-C. I think it will be fascinating to learn about the sequences and activities of these toxins that are circulating in bat populations. Stay tuned to the Elde lab for more on this in the future!

Have your say

Your email address will not be published. Required fields are marked *

This site uses Akismet to reduce spam. Learn how your comment data is processed.

Sign up to customise the site to your preferences and to receive alerts

Register here

Also in the biochemistry category:

Structural basis of respiratory complexes adaptation to cold temperatures

Young-Cheul Shin, Pedro Latorre-Muro, Amina Djurabekova, et al.



Selected by Pamela Ornelas

Lens Placode Modulates Extracellular Matrix Formation During Early Eye Development

Cecília G. De Magalhães, Ales Cvekl, Ruy G. Jaeger, et al.



Selected by Bhaval Parmar

Generalized Biomolecular Modeling and Design with RoseTTAFold All-Atom

Rohith Krishna, Jue Wang, Woody Ahern, et al.



Selected by Saanjbati Adhikari

Also in the evolutionary biology category:

A long non-coding RNA at the cortex locus controls adaptive colouration in butterflies

Luca Livraghi, Joseph J. Hanly, Elizabeth Evans, et al.

AND

The ivory lncRNA regulates seasonal color patterns in buckeye butterflies

Richard A. Fandino, Noah K. Brady, Martik Chatterjee, et al.

AND

A micro-RNA drives a 100-million-year adaptive evolution of melanic patterns in butterflies and moths

Shen Tian, Tirtha Das Banerjee, Jocelyn Liang Qi Wee, et al.



Selected by Isabella Cisneros

A complex Plasmodium falciparum cryptotype circulating at low frequency across the African continent

Olivo Miotto, Alfred Amambua-Ngwa, Lucas Amenga-Etego, et al.



Selected by Alejandra Herbert Leffler's Lab

Evolution of tandem repeats in putative CSP to enhance its function: A recent and exclusive event in Plasmodium vivax in India

Manoswini Dash, Veena Pande, Aparup Das, et al.



Selected by Alejandra Herbert Leffler's Lab

Also in the microbiology category:

RIPK3 coordinates RHIM domain-dependent inflammatory transcription in neurons

Sigal B. Kofman, Lan H. Chu, Joshua M. Ames, et al.



Selected by Zoie Magri

Digital Microbe: A Genome-Informed Data Integration Framework for Collaborative Research on Emerging Model Organisms

Iva Veseli, Zachary S. Cooper, Michelle A. DeMers, et al.



Selected by Benjamin Dominik Maier, Jennifer Ann Black

Mixed Alkyl/Aryl Phosphonates Identify Metabolic Serine Hydrolases as Antimalarial Targets

John M. Bennett, Sunil K. Narwal, Stephanie Kabeche, et al.



Selected by Zhang-He Goh

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

Preprint Peer Review – Biochemistry Course at UFRJ, Brazil

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 biochemistry 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

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
Close