Prevalence and polymorphism of a mussel transmissible cancer in Europe.

Transmissible cancers are parasitic malignant cell lineages that acquired the ability to infect new hosts from the same species, or sometimes related species. First described in dogs and Tasmanian devils, transmissible cancers were later discovered in some marine bivalves affected by a leukemia-like disease. In Mytilus mussels, two lineages of Bivalve Transmissible Neoplasia (BTN), both emerged in a M. trossulus founder individual, have been described to date (MtrBTN1 and MtrBTN2). Here, we performed an extensive screening of genetic chimerism, a hallmark of transmissible cancer, by genotyping hundred SNPs of thousands of European Mytilus mussels. The genetic analysis allowed us to simultaneously obtain the genotype of hosts -M. edulis, M. galloprovincialis or hybrids- and the genotype of tumors of heavily infected individuals. In addition, a subset of individuals were systematically genotyped and analysed by histology in order to screen for possible non-transmissible cancers. We detected MtrBTN2 at low prevalence in M. edulis, and also in M. galloprovincialis and hybrids although at a much lower prevalence. No MtrBTN1 or new BTN were found but a few individuals with non-transmissible neoplasia were observed at a single polluted site on the same sampling date. We observed a diversity of MtrBTN2 genotypes that appeared more introgressed or more ancestral than MtrBTN1 and reference healthy M. trossulus individuals. The observed polymorphism is most likely due to somatic null alleles caused by structural variations or point mutations in primer-binding sites leading to enhanced detection of the host alleles. Despite low prevalence, two divergent sublineages, confirmed by mtCOI sequences, are co-spreading in the same geographic area, suggesting a complex diversification of MtrBTN2 since its emergence and host species shift.

传染性癌症是寄生性的恶性细胞谱系，它们获得了感染同一物种或有时相关物种的新宿主的能力。传染性癌症最初在狗和袋獾中被发现，后来在一些患有类似白血病疾病的海洋双壳类动物中也被发现。在贻贝中，迄今为止已经描述了两种双壳类传染性肿瘤（BTN）谱系，它们都起源于一个紫贻贝（M. trossulus）的创始个体（MtrBTN1和MtrBTN2）。在这里，我们通过对数千只欧洲贻贝的数百个单核苷酸多态性（SNP）进行基因分型，对基因嵌合现象（传染性癌症的一个标志）进行了广泛的筛选。基因分析使我们能够同时获得宿主（紫贻贝、地中海贻贝或杂交种）的基因型以及重度感染个体的肿瘤基因型。此外，对一部分个体进行了系统的基因分型和组织学分析，以筛选可能的非传染性癌症。我们在紫贻贝中检测到低患病率的MtrBTN2，在地中海贻贝和杂交种中也有发现，但患病率要低得多。没有发现MtrBTN1或新的BTN，但在同一采样日期的一个污染地点观察到了少数患有非传染性肿瘤的个体。我们观察到MtrBTN2基因型的多样性，与MtrBTN1和参考的健康紫贻贝个体相比，它们似乎更具基因渗入性或更具原始性。观察到的多态性很可能是由于引物结合位点的结构变异或点突变导致的体细胞无效等位基因，从而增强了对宿主等位基因的检测。尽管患病率较低，但通过线粒体细胞色素c氧化酶亚基I（mtCOI）序列证实的两个不同的亚谱系在同一地理区域共同传播，这表明自MtrBTN2出现和宿主物种转变以来，其发生了复杂的多样化。