Université de Perpignan Via Domitia, Perpignan, France.
PLoS Pathog. 2013;9(8):e1003571. doi: 10.1371/journal.ppat.1003571. Epub 2013 Aug 29.
The digenetic trematode Schistosoma mansoni is a human parasite that uses the mollusc Biomphalaria glabrata as intermediate host. Specific S. mansoni strains can infect efficiently only certain B. glabrata strains (compatible strain) while others are incompatible. Strain-specific differences in transcription of a conserved family of polymorphic mucins (SmPoMucs) in S. mansoni are the principle determinants for this compatibility. In the present study, we investigated the bases of the control of SmPoMuc expression that evolved to evade B. glabrata diversified antigen recognition molecules. We compared the DNA sequences and chromatin structure of SmPoMuc promoters of two S. mansoni strains that are either compatible (C) or incompatible (IC) with a reference snail host. We reveal that although sequence differences are observed between active promoter regions of SmPoMuc genes, the sequences of the promoters are not diverse and are conserved between IC and C strains, suggesting that genetics alone cannot explain the evolution of compatibility polymorphism. In contrast, promoters carry epigenetic marks that are significantly different between the C and IC strains. Moreover, we show that modifications of the structure of the chromatin of the parasite modify transcription of SmPoMuc in the IC strain compared to the C strain and correlate with the presence of additional combinations of SmPoMuc transcripts only observed in the IC phenotype. Our results indicate that transcription polymorphism of a gene family that is responsible for an important adaptive trait of the parasite is epigenetically encoded. These strain-specific epigenetic marks are heritable, but can change while the underlying genetic information remains stable. This suggests that epigenetic changes may be important for the early steps in the adaptation of pathogens to new hosts, and might be an initial step in adaptive evolution in general.
曼氏血吸虫是一种寄生人体的双腔吸虫,其中间宿主是淡水螺——光滑小舌钉螺。曼氏血吸虫的某些特定株系仅能有效地感染某些光滑小舌钉螺株系(相容株系),而其他株系则不兼容。曼氏血吸虫中保守的多态黏蛋白家族(SmPoMucs)的转录在菌株特异性方面存在差异,是决定这种相容性的主要因素。在本研究中,我们研究了 SmPoMuc 表达调控的基础,这些调控机制的进化是为了逃避光滑小舌钉螺多样化的抗原识别分子。我们比较了两种曼氏血吸虫株系的 SmPoMuc 启动子的 DNA 序列和染色质结构,这两种株系与参考螺宿主分别是相容的(C)或不相容的(IC)。我们揭示了尽管在 SmPoMuc 基因的活性启动子区域观察到序列差异,但启动子的序列并没有多样化,在 IC 和 C 株系之间是保守的,这表明遗传因素本身并不能解释相容性多态性的进化。相比之下,启动子携带的表观遗传标记在 C 和 IC 株系之间存在显著差异。此外,我们还表明,寄生虫染色质结构的修饰改变了 IC 株系中 SmPoMuc 的转录,与仅在 IC 表型中观察到的额外 SmPoMuc 转录本组合的存在相关。我们的研究结果表明,一个负责寄生虫重要适应性特征的基因家族的转录多态性是由表观遗传编码的。这些菌株特异性的表观遗传标记是可遗传的,但在潜在遗传信息保持稳定的情况下,它们可以发生变化。这表明,表观遗传变化可能对病原体适应新宿主的早期步骤很重要,并且可能是一般适应性进化的初始步骤。