Biba Dmitry A, Makarova Kira S, Wolf Yuri I, Waldron Leavi, Koonin Eugene V, Rochman Nash D
Computational Biology Branch, Division of Intramural Research, National Library of Medicine, National Institutes of Health, Bethesda, MD.
Oak Ridge Institute for Science and Education, Oak Ridge, TN.
bioRxiv. 2024 Nov 5:2024.11.05.622165. doi: 10.1101/2024.11.05.622165.
Prokaryote evolution is driven in large part by the incessant arms race with viruses. Genomic investments in antivirus defense can be coarsely classified into two categories, immune systems that abrogate virus reproduction resulting in clearance, and altruistic programmed cell death (PCD) systems. Prokaryotic defense systems are enormously diverse, as revealed by an avalanche of recent discoveries, but the basic ecological determinants of defense strategy remain poorly understood. Through mathematical modeling of defense against lytic virus infection, we identify two principal determinants of optimal defense strategy and, through comparative genomics, we test this model by measuring the genomic investment into immunity vs PCD among diverse bacteria and archaea. First, as viral pressure grows, immunity becomes the preferred defense strategy. Second, as host population size grows, PCD becomes the preferred strategy. We additionally predict that, although optimal strategy typically involves investment in both PCD and immunity, overinvestment in immunity can result in system antagonism, increasing the probability a PCD-competent cell will lyse due to infection. Together these findings indicate that, generally, PCD is preferred at low multiplicity of infection (MOI) and immunity is preferred at high MOI, and that the landscape of prokaryotic antivirus defense is substantially more complex than previously suspected.
原核生物的进化在很大程度上是由与病毒持续不断的军备竞赛驱动的。在抗病毒防御方面的基因组投入大致可分为两类:一类是能够消除病毒繁殖从而实现清除的免疫系统,另一类是利他性程序性细胞死亡(PCD)系统。正如近期大量发现所揭示的那样,原核生物的防御系统极为多样,但防御策略的基本生态决定因素仍知之甚少。通过对针对裂解性病毒感染的防御进行数学建模,我们确定了最佳防御策略的两个主要决定因素,并通过比较基因组学,通过测量不同细菌和古菌在免疫与PCD方面的基因组投入来检验该模型。首先,随着病毒压力的增加,免疫成为首选的防御策略。其次,随着宿主种群规模的增大,PCD成为首选策略。我们还预测,尽管最佳策略通常涉及对PCD和免疫的投入,但对免疫的过度投入可能会导致系统拮抗,增加具有PCD能力的细胞因感染而裂解的概率。这些发现共同表明,一般来说,在低感染复数(MOI)时PCD是首选,在高MOI时免疫是首选,而且原核生物抗病毒防御的格局比之前所怀疑的要复杂得多。