Multiple Stages of Evolutionary Change in Anthrax Toxin Receptor Expression in Humans

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Nov 16

PMID 34782625

Citations 3

Authors

Lauren A Choate

Gilad Barshad

Pierce W McMahon

Iskander Said

Edward J Rice

Paul R Munn

James J Lewis

Charles G Danko

Affiliations

Soon will be listed here.

Abstract

The advent of animal husbandry and hunting increased human exposure to zoonotic pathogens. To understand how a zoonotic disease may have influenced human evolution, we study changes in human expression of anthrax toxin receptor 2 (ANTXR2), which encodes a cell surface protein necessary for Bacillus anthracis virulence toxins to cause anthrax disease. In immune cells, ANTXR2 is 8-fold down-regulated in all available human samples compared to non-human primates, indicating regulatory changes early in the evolution of modern humans. We also observe multiple genetic signatures consistent with recent positive selection driving a European-specific decrease in ANTXR2 expression in multiple tissues affected by anthrax toxins. Our observations fit a model in which humans adapted to anthrax disease following early ecological changes associated with hunting and scavenging, as well as a second period of adaptation after the rise of modern agriculture.

Citing Articles

Identification of Potential Therapeutic Targets Against Anthrax-Toxin-Induced Liver and Heart Damage.

Wu L, Chen Y, Yan Y, Wang H, Guy C, Carney J Toxins (Basel). 2025; 17(2).

PMID: 39998071 PMC: 11861023. DOI: 10.3390/toxins17020054.

Investigating the Influence of Gene Mutations on Protective Antigen Binding for Heightened Anthrax Resistance.

Archana C, Sekar Y, Suresh K, Subramaniam S, Sagar N, Rani S Genes (Basel). 2024; 15(4).

PMID: 38674361 PMC: 11049084. DOI: 10.3390/genes15040426.

Dissection of core promoter syntax through single nucleotide resolution modeling of transcription initiation.

He A, Danko C bioRxiv. 2024; .

PMID: 38559255 PMC: 10979970. DOI: 10.1101/2024.03.13.583868.

Multiple stages of evolutionary change in anthrax toxin receptor expression in humans.

Choate L, Barshad G, McMahon P, Said I, Rice E, Munn P Nat Commun. 2021; 12(1):6590.

PMID: 34782625 PMC: 8592990. DOI: 10.1038/s41467-021-26854-z.

References

Schmiedel B, Singh D, Madrigal A, Valdovino-Gonzalez A, White B, Zapardiel-Gonzalo J . Impact of Genetic Polymorphisms on Human Immune Cell Gene Expression. Cell. 2018; 175(6):1701-1715.e16. PMC: 6289654. DOI: 10.1016/j.cell.2018.10.022. View

LaForce F . Woolsorters' disease in England. Bull N Y Acad Med. 1978; 54(10):956-63. PMC: 1807561. View

Danko C, Hyland S, Core L, Martins A, Waters C, Lee H . Identification of active transcriptional regulatory elements from GRO-seq data. Nat Methods. 2015; 12(5):433-8. PMC: 4507281. DOI: 10.1038/nmeth.3329. View

Hsieh T, Cattoglio C, Slobodyanyuk E, Hansen A, Rando O, Tjian R . Resolving the 3D Landscape of Transcription-Linked Mammalian Chromatin Folding. Mol Cell. 2020; 78(3):539-553.e8. PMC: 7703524. DOI: 10.1016/j.molcel.2020.03.002. View

Pybus M, DallOlio G, Luisi P, Uzkudun M, Carreno-Torres A, Pavlidis P . 1000 Genomes Selection Browser 1.0: a genome browser dedicated to signatures of natural selection in modern humans. Nucleic Acids Res. 2013; 42(Database issue):D903-9. PMC: 3965045. DOI: 10.1093/nar/gkt1188. View

Cannavo E, Koelling N, Harnett D, Garfield D, Casale F, Ciglar L . Genetic variants regulating expression levels and isoform diversity during embryogenesis. Nature. 2016; 541(7637):402-406. DOI: 10.1038/nature20802. View

Perez-Pinera P, Kocak D, Vockley C, Adler A, Kabadi A, Polstein L . RNA-guided gene activation by CRISPR-Cas9-based transcription factors. Nat Methods. 2013; 10(10):973-6. PMC: 3911785. DOI: 10.1038/nmeth.2600. View

Choate L, Barshad G, McMahon P, Said I, Rice E, Munn P . Multiple stages of evolutionary change in anthrax toxin receptor expression in humans. Nat Commun. 2021; 12(1):6590. PMC: 8592990. DOI: 10.1038/s41467-021-26854-z. View

Tome J, Tippens N, Lis J . Single-molecule nascent RNA sequencing identifies regulatory domain architecture at promoters and enhancers. Nat Genet. 2018; 50(11):1533-1541. PMC: 6422046. DOI: 10.1038/s41588-018-0234-5. View

10.

Harrison G, Sanz J, Boulais J, Mina M, Grenier J, Leng Y . Natural selection contributed to immunological differences between hunter-gatherers and agriculturalists. Nat Ecol Evol. 2019; 3(8):1253-1264. PMC: 6684323. DOI: 10.1038/s41559-019-0947-6. View

11.

Kuhn R, Haussler D, Kent W . The UCSC genome browser and associated tools. Brief Bioinform. 2012; 14(2):144-61. PMC: 3603215. DOI: 10.1093/bib/bbs038. View

12.

Ludwig M, Bergman C, Patel N, Kreitman M . Evidence for stabilizing selection in a eukaryotic enhancer element. Nature. 2000; 403(6769):564-7. DOI: 10.1038/35000615. View

13.

Rao S, Huntley M, Durand N, Stamenova E, Bochkov I, Robinson J . A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell. 2014; 159(7):1665-80. PMC: 5635824. DOI: 10.1016/j.cell.2014.11.021. View

14.

Marcus J, Novembre J . Visualizing the geography of genetic variants. Bioinformatics. 2016; 33(4):594-595. PMC: 5408806. DOI: 10.1093/bioinformatics/btw643. View

15.

Liu S, Zhang Y, Moayeri M, Liu J, Crown D, Fattah R . Key tissue targets responsible for anthrax-toxin-induced lethality. Nature. 2013; 501(7465):63-8. PMC: 4080305. DOI: 10.1038/nature12510. View

16.

Durand N, Shamim M, Machol I, Rao S, Huntley M, Lander E . Juicer Provides a One-Click System for Analyzing Loop-Resolution Hi-C Experiments. Cell Syst. 2016; 3(1):95-8. PMC: 5846465. DOI: 10.1016/j.cels.2016.07.002. View

17.

Lv F, Agha S, Kantanen J, Colli L, Stucki S, Kijas J . Adaptations to climate-mediated selective pressures in sheep. Mol Biol Evol. 2014; 31(12):3324-43. PMC: 4245822. DOI: 10.1093/molbev/msu264. View

18.

Li H, Durbin R . Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics. 2010; 26(5):589-95. PMC: 2828108. DOI: 10.1093/bioinformatics/btp698. View

19.

Golden H, Watson L, Lal H, Verma S, Foster D, Kuo S . Anthrax toxin: pathologic effects on the cardiovascular system. Front Biosci (Landmark Ed). 2009; 14(6):2335-57. DOI: 10.2741/3382. View

20.

Snyder-Mackler N, Sanz J, Kohn J, Brinkworth J, Morrow S, Shaver A . Social status alters immune regulation and response to infection in macaques. Science. 2016; 354(6315):1041-1045. PMC: 5498102. DOI: 10.1126/science.aah3580. View