Bugs in Transition: The Dynamic World of Wolbachia in Insects
Bugs in Transition: The Dynamic World of Wolbachia in Insects
复制标题
转变中的错误：昆虫中沃尔巴克氏体的动态世界
作者：
W. Miller
下一代测序工具的出现揭示了一个意想不到的高度复杂的隐藏微生物乘客宇宙，这些微生物乘客与宿主短暂或永久相关，以下称为共生体。在自然条件下，这些共生体通常受到内在和外在因素的严格控制，以低密度出现和/或被限制在特殊组织中，例如它们自身的复制能力、营养和压力以及宿主免疫能力。
然而，当前共生研究的主要问题之一是，这些微生物乘客在多大程度上影响宿主表型，如健康、繁殖力、病原体抵抗力，甚至行为。在本期 PLOS Genetics 中，Luis Teixeira 及其同事 [1] 非常优雅地开始回答共生研究中的一些基本问题。他们的研究重点是属于沃尔巴克氏菌属的细胞内细菌，这是研究最深入的共生体之一。沃尔巴克氏体存在于高达 70% 的昆虫物种和许多陆生节肢动物中，并通过受感染雌性的卵垂直传播给其后代。为了提高其在宿主群体中传播的成功率，沃尔巴克氏体可以通过充当生殖寄生虫来操纵宿主的生殖生物学，增强受感染雌性的适应性和繁殖力，使它们能够在自然界中迅速击败未感染的雌性[2]。
但是，一旦宿主群体中的大多数人已经被感染并且细菌的传播停止时，感染会发生什么？在某些情况下，已经表明，在其进化过程中，沃尔巴克氏体已经将其表型从生殖寄生转变为专性互利共生，其中共生体承担了重要的宿主功能，例如卵子发生、营养，甚至配偶识别[3]-[5]。哪种外在和/或内在因素触发表型转变，它们的遗传基础是什么？最近的一项研究表明，在自然界中，仅 20 年之内，沃尔巴克氏体就可以通过增强受感染的模拟果蝇雌性的繁殖力，从一种昂贵的生殖寄生虫转变为一种互利共生生物 [6]。
然而，最令人费解的观察结果之一是，20 世纪全球范围内，一种名为 wMelCS 的沃尔巴克氏体祖先菌株被果蝇中密切相关的变体 wMel 取代，果蝇是研究昆虫宿主-共生体相互作用的顶级遗传模型系统 [7], [8]。尽管无论是在实验室还是在自然界中，沃尔巴克氏菌菌株都不会在其各自的本地宿主中引起任何显着水平的生殖寄生，但这两种菌株在全世界黑腹果蝇中持续存在，表明它们具有某些宿主功能。此外，两项独立研究表明，两种沃尔巴克氏体菌株均具有显着的病毒保护作用[9]、[10]。令人印象深刻的是，黑腹果蝇沃尔巴克氏体还可以保护不天然携带沃尔巴克氏体的人工转染蚊子免受致病性 RNA 病毒（例如登革热和基孔肯雅热）的侵害 [11]。黑腹果蝇的第三种沃尔巴克氏菌菌株 wMelPop 具有更强的病毒抵抗力，它是一种致病性沃尔巴克氏体变种，最初是在实验室辐射诱变后出现的。这种有毒的沃尔巴克氏菌菌株最近成为一个主要的研究焦点，因为它在体细胞宿主组织中大量过度复制（由于成体组织中受感染细胞的外观像爆米花，因此被称为“爆米花”），从而显着缩短宿主的寿命[12]。将wMelPop转入登革热埃及伊蚊的主要载体后，结果表明wMelPop的缩短寿命作用在这一医学上重要的昆虫系统中也很明显[13]。病毒保护、寿命缩短和母体传播能力的结合使得黑腹果蝇沃尔巴克氏菌菌株成为生物学上合理的害虫控制策略的主要候选者。然而，除了它们在节肢动物传播疾病控制方面令人印象深刻的应用能力之外，我们目前对以下主要问题缺乏了解：这三个菌株之间的基因型和表型差异是什么，以及为什么 wMel 菌株在最近全球范围内取代了 wMelCS？更好地了解其遗传基础及其短期成本效益动态对于进一步将沃尔巴克氏体应用于异源害虫系统的研究至关重要。
为此，Texeira 及其同事研究了黑腹果蝇短期沃尔巴克氏体动力学的分子和表型基础。首先，他们将三种沃尔巴克氏体变种 wMelCS、wMel 和 wMelPop 杂交到共同的遗传果蝇背景中，以排除任何核背景效应。然后，他们仔细分析了它们在沃尔巴克氏体存在和不存在的情况下抑制果蝇 C 病毒和羊群病毒感染的能力。他们发现，与感染 wMel 变体的果蝇相比，祖先 wMelCS 变体增殖的密度更高，并且对这两种 RNA 病毒具有更强的保护作用。他们还发现，携带祖先 wMelCS 感染的果蝇虽然更能抵御病毒感染，但付出的代价是寿命比感染 wMel 的果蝇略短（图 1）。因此，他们提出，祖先的高成本菌株 wMelCS（由于滴度高而缩短寿命）最近在自然界中已被成本较低的沃尔巴克氏体变体 wMel 所取代，后者仍然可以显着保护宿主免受病毒感染，但以较低的密度复制，寿命成本也较低。
图1
沃尔巴克氏体在黑腹果蝇自然种群（下）和实验室品系（上）中的进化成本效益动态。
最后，他们通过将单系 wMelCS Wolbachia 群的表型与基因型联系起来，追踪了从共生到毒力转变的遗传基础。通过对互惠性 wMelCS 样基因组与致病性 wMelPop 基因组进行深思熟虑的比较分析，他们发现这两种表型不同的沃尔巴克氏菌菌株形成了一个单系群，其主要差异仅在一个基因组区域：wMelPop 中编码 8 种沃尔巴克氏体蛋白的 21 kb 区域扩增了 7 倍。这些数据强烈暗示，这个所谓的“Octomom 区域”内一个或多个基因的选择性扩增很可能是导致有毒爆米花表型表达的原因。
这项令人印象深刻的研究提出了许多额外的问题，这些问题不仅与共生研究高度相关，而且与未来的应用方面也高度相关：wMelPop Octomom 区域的八个候选基因中的哪一个足以触发沃尔巴克氏体致病性？共生体引导的病毒宿主保护的遗传基础及其强度是什么？最后，在不久的将来，在自然选择的作用下，在蚊子等新宿主系统中，预计会发生什么样的表型和遗传沃尔巴克氏体转变？敬请关注！我们很可能非常接近实时监测宿主-共生体相互作用的短期进化动态。
The availability of Next Generation Sequencing tools has uncovered an unexpected and highly complex universe of hidden microbial passengers that are transiently or permanently associated with their hosts, hereafter called symbionts. Under natural conditions, these symbionts are often tightly controlled to occur at low densities and/or are restricted to special tissues by intrinsic and extrinsic factors, such as their own replication capacity, nutrition, and stress, as well as host immune competence.
One of the main questions of current symbiosis research is, however, to what extent these microbial passengers affect host phenotypes such as fitness, fecundity, pathogen resistance, or even behavior. In this issue of PLOS Genetics, Luis Teixeira and colleagues [1] have, very elegantly, started to answer some of these essential questions in symbiosis research. The focus of their research is on intracellular bacteria belonging to the genus Wolbachia, one of the most intensively studied symbionts. Wolbachia are found in up to 70% of insect species and in many terrestrial arthropods, and are vertically transmitted with the egg from an infected female to her progeny. In order to enhance their spreading success throughout host populations, Wolbachia can manipulate host reproductive biology by acting as a reproductive parasite, enhancing fitness and fecundity of infected females, enabling them to outcompete uninfected females rapidly in nature [2].
But what happens to the infection as soon as the majority of individuals within a host population are already infected and the spreading of the bacteria comes to a stop? In some cases it has been shown that, in their evolutionary past, Wolbachia have changed their phenotype from reproductive parasitism to obligate mutualism, where the symbiont takes on essential host functions for, e.g., oogenesis, nutrition, or even mate recognition [3]–[5]. Which kind of extrinsic and/or intrinsic factors trigger phenotypic transitions, and what is their genetic basis? In a recent study it was shown that within only 20 years in nature, Wolbachia can transform from a costly reproductive parasite into a mutualist by enhancing fecundity of infected Drosophila simulans females [6].
One of the most puzzling observations, however, is the worldwide replacement during the 20th century of one ancestral Wolbachia strain named wMelCS with the closely related variant wMel in Drosophila melanogaster, the top genetic model system for studying insect host-symbiont interactions [7], [8]. Although neither Wolbachia strain causes any significant level of reproductive parasitism in its respective native host, either in the laboratory or in nature, both persist globally in D. melanogaster at high frequencies worldwide, suggesting they serve some host functions. Moreover, two independent studies have shown that both Wolbachia strains confer significant virus protection [9], [10]. Impressively, D. melanogaster Wolbachia also protects artificially transinfected mosquitos that do not naturally carry Wolbachia from pathogenic RNA viruses, such as Dengue and Chikungunya [11]. A third Wolbachia strain of D. melanogaster that provides even stronger virus resistance is wMelPop, a pathogenic Wolbachia variant that originally emerged after radiation mutagenesis in the laboratory. This virulent Wolbachia strain has recently become a major research focus because it overreplicates massively in somatic host tissues (it is named “popcorn” due to the popcorn-like appearance of infected cells in adult tissues) and hence significantly shortens the lifespan of its host [12]. After transferring wMelPop into the main vector of dengue fever Aedes aegypti, it was shown that the life-shortening effect of wMelPop is also manifest in this medically important insect system [13]. The combination of virus protection, life shortening, and the capacity of maternal spreading render D. melanogaster Wolbachia strains prime candidates for biologically sound insect pest control strategies. Besides their impressive applied capacities for arthropod-borne disease control, however, we currently lack understanding on the following main questions: what are the genotypic and phenotypic differences between the three strains, and why did the wMel strain replace wMelCS globally in the recent past? A better understanding of their genetic basis and their short-term cost–benefit dynamics will be pivotal for further Wolbachia-applied studies in heterologous pest systems.
To this end, Texeira and colleagues studied the molecular and phenotypic basis of short-term Wolbachia dynamics in D. melanogaster. First, they crossed the three Wolbachia variants wMelCS, wMel, and wMelPop into a common genetic fly background in order to exclude any nuclear background effects. Then they carefully assayed for their capacity to suppress viral infections of the Drosophila C virus and Flock house virus in the presence and absence of Wolbachia. They found that the ancestral wMelCS variants proliferate to higher densities and confer greater protection against the two RNA viruses than do flies infected with wMel variants. They also found that flies carrying the ancestral wMelCS infection, although more protected against viral infections, pay a price by living slightly shorter lives than wMel-infected flies (Figure 1). They therefore propose that the ancestral high-cost strain wMelCS (life-shortening due to high titer) has been replaced in nature recently by the less costly Wolbachia variant wMel, which still protects the host significantly from viral infections but replicates at lower densities with lower costs on longevity.
Figure 1
Evolutionary cost–benefit dynamics of Wolbachia in natural populations (below) and laboratory lines (above) of Drosophila melanogaster.
Finally, they trace the genetic basis for the transition from symbiosis to virulence by linking phenotype to genotype in the monophyletic wMelCS Wolbachia group. Through their thoughtful comparative analysis of mutualistic wMelCS-like versus pathogenic wMelPop genomes, they found that these two phenotypically distinct Wolbachia strains form a monophyletic group that mainly differ in only one genomic region: a 7-fold amplification of a 21-kb region in wMelPop encoding eight Wolbachia proteins. These data strongly imply that the selective amplification of one or more genes within this so-called “Octomom region” is quite likely responsible for the expression of the virulent Popcorn phenotype.
This impressive study opens numerous additional questions that will be highly relevant for symbiosis research but also for future applied aspects: Which of the eight candidate genes of the Octomom region of wMelPop are sufficient for triggering Wolbachia pathogenicity? What are the genetic bases for symbiont-directed viral host protection and its strength? And finally, what kind of phenotypic and genetic Wolbachia transitions can be expected to happen in novel host systems such as mosquitos in the near future under natural selection? Stay tuned! It is likely that we are pretty close to monitoring short-term evolutionary dynamics of host–symbiont interactions in real time.
DOI：
10.1073/pnas.94.20.10792
发表时间：
1997-09-30
影响因子：
11.1
作者：
Min, KT;Benzer, S
通讯作者：
Benzer, S