Ye Yixin H, Chenoweth Stephen F, McGraw Elizabeth A
School of Biological Sciences, The University of Queensland, St. Lucia, Queensland, Australia.
PLoS Pathog. 2009 Apr;5(4):e1000385. doi: 10.1371/journal.ppat.1000385. Epub 2009 Apr 17.
Drosophila harbor substantial genetic variation for antibacterial defense, and investment in immunity is thought to involve a costly trade-off with life history traits, including development, life span, and reproduction. To understand the way in which insects invest in fighting bacterial infection, we selected for survival following systemic infection with the opportunistic pathogen Pseudomonas aeruginosa in wild-caught Drosophila melanogaster over 10 generations. We then examined genome-wide changes in expression in the selected flies relative to unselected controls, both of which had been infected with the pathogen. This powerful combination of techniques allowed us to specifically identify the genetic basis of the evolved immune response. In response to selection, population-level survivorship to infection increased from 15% to 70%. The evolved capacity for defense was costly, however, as evidenced by reduced longevity and larval viability and a rapid loss of the trait once selection pressure was removed. Counter to expectation, we observed more rapid developmental rates in the selected flies. Selection-associated changes in expression of genes with dual involvement in developmental and immune pathways suggest pleiotropy as a possible mechanism for the positive correlation. We also found that both the Toll and the Imd pathways work synergistically to limit infectivity and that cellular immunity plays a more critical role in overcoming P. aeruginosa infection than previously reported. This work reveals novel pathways by which Drosophila can survive infection with a virulent pathogen that may be rare in wild populations, however, due to their cost.
果蝇在抗菌防御方面存在大量遗传变异,并且人们认为在免疫方面的投入涉及到与包括发育、寿命和繁殖在内的生活史特征之间的昂贵权衡。为了了解昆虫对抗细菌感染的投入方式,我们在10代的时间里,对野生捕获的黑腹果蝇用机会性病原体铜绿假单胞菌进行全身感染后选择存活个体。然后,我们检查了所选果蝇相对于未选对照(两者均已感染病原体)的全基因组表达变化。这种强大的技术组合使我们能够具体确定进化后的免疫反应的遗传基础。作为对选择的响应,群体水平上对感染的存活率从15%提高到了70%。然而,进化后的防御能力是有代价的,寿命和幼虫活力降低以及一旦去除选择压力该性状迅速丧失就证明了这一点。与预期相反,我们在所选果蝇中观察到了更快的发育速度。在发育和免疫途径中双重参与的基因的表达与选择相关的变化表明基因多效性是这种正相关的一种可能机制。我们还发现Toll和Imd途径协同作用以限制感染性,并且细胞免疫在克服铜绿假单胞菌感染中发挥着比先前报道更关键的作用。这项工作揭示了果蝇能够在感染一种在野生种群中可能罕见的致病病原体后存活的新途径,然而,由于其代价,这种情况可能很少见。