Instituto de Parasitología y Biomedicina López-Neyra (IPBLN), Consejo Superior de Investigaciones Científicas, Granada, Spain.
Brief Funct Genomics. 2019 Sep 24;18(5):313-357. doi: 10.1093/bfgp/elz007.
Malaria parasites face dynamically changing environments and strong selective constraints within human and mosquito hosts. To survive such hostile and shifting conditions, Plasmodium switches transcriptional programs during development and has evolved mechanisms to adjust its phenotype through heterogeneous patterns of gene expression. In vitro studies on culture-adapted isolates have served to set the link between chromatin structure and functional gene expression. Yet, experimental evidence is limited to certain stages of the parasite in the vertebrate, i.e. blood, while the precise mechanisms underlying the dynamic regulatory landscapes during development and in the adaptation to within-host conditions remain poorly understood. In this review, we discuss available data on transcriptional and epigenetic regulation in Plasmodium mosquito stages in the context of sporogonic development and phenotypic variation, including both bet-hedging and environmentally triggered direct transcriptional responses. With this, we advocate the mosquito offers an in vivo biological model to investigate the regulatory networks, transcription factors and chromatin-modifying enzymes and their modes of interaction with regulatory sequences, which might be responsible for the plasticity of the Plasmodium genome that dictates stage- and cell type-specific blueprints of gene expression.
疟原虫面临着动态变化的环境和人类及蚊子宿主内的强烈选择压力。为了在这种恶劣和不断变化的环境中生存，疟原虫在发育过程中切换转录程序，并通过基因表达的异质模式进化出调节表型的机制。体外培养适应株的研究已经将染色质结构和功能基因表达联系起来。然而，实验证据仅限于脊椎动物中寄生虫的某些阶段，即血液，而在发育过程中以及对体内条件的适应过程中动态调节景观背后的精确机制仍知之甚少。在这篇综述中，我们讨论了疟原虫蚊期在孢子发生发育和表型变异过程中转录和表观遗传调控的现有数据，包括避险和环境触发的直接转录反应。通过这些，我们主张蚊子提供了一个体内生物学模型，用于研究调节网络、转录因子和染色质修饰酶及其与调节序列相互作用的模式，这些可能是决定疟原虫基因组可塑性的原因，而基因组的可塑性决定了基因表达的阶段和细胞类型特异性蓝图。
