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

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.

Prospect of using B. anthracis exotoxin in the design of anti-selective emergency preparations

“…Despite the effectiveness of modern vaccines, scientists are searching for the development of the most areactogenic preparations, namely the improvement of anthrax vaccines to reduce irritation and inflammation at the injection site. Similar reactions occur in case of an edematous and lethal factor [29][30][31]. Another important criterion is an increase in the duration of immunity, an increase in the production of protective antigen by vaccine producing strains.…”

“…The BioThrax vaccine in the US (formerly known as AVA) and the similar AVP vaccine in the UK are alum-adsorbed culture filtrates of vaccine strains of the anthrax pathogen that contain PA. Earlier studies have shown that exotoxin immunization of various animal models provides protection against anthrax infection [29][30][31]. A post-vaccination correlation of PA antibody titres has also been established [32; 33].…”

“…Therefore, the search for both exotoxin producers and compositions of exotoxin compounds continues [37][38][39], both according to indicators of an allergic reaction and reduction of post-vaccination consequences [34][35][36], also considering the duration of the protective effect and improving the compositions [27; 28]. Immunization of animals [29][30][31] shows a more efficacious influence of exotoxin as the main component of the preparation or the main ingredient of the composition [32; 33].…”

Homo medicus: The transition to meat eating increased pathogen pressure and the use of pharmacological plants in Homo

“…Similar evolution of these genes in apes has not occurred, nor has there been recent evolution of these genes in humans (Moon et al, 2018), suggesting that the selection pressure was increased carnivory‐rated spillover c. 2 mya (Khan et al, 2020). There is also evidence that resistance to Bacillus anthracis , a zoonotic bacterium that spills over from ruminants into humans, evolved early in modern human evolution (Choate et al, 2021). Finally, unlike chimpanzees and other vertebrates, humans have three high frequency apolipoprotein E alleles, which are linked to meat‐eating and improved immune defense, among other things (Finch & Stanford, 2004; Vitek et al, 2009; cf.…”

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

“…Transcriptional regulation, the mechanism by which cells dynamically modulate the expression of each gene in their genome, plays a pivotal role in nearly every cellular process and is among the most important molecular pathways underlying variation in complex traits [1][2][3][4][5][6][7][8][9]. Transcription is controlled by at least two classes of transcription factor protein, which bind to characteristic DNA sequence motifs and work in concert to tune the rates of early steps during the RNA polymerase II (Pol II) transcription cycle [10].…”