Molecular Genetics of Heterokaryon Incompatibility in Filamentous Ascomycetes

Filamentous fungi spontaneously undergo vegetative cell fusion events within but also between individuals. These cell fusions (anastomoses) lead to cytoplasmic mixing and to the formation of vegetative heterokaryons (i.e., cells containing different nuclear types). The viability of these heterokaryons is genetically controlled by specific loci termed het loci (for heterokaryon incompatibility). Heterokaryotic cells formed between individuals of unlike het genotypes undergo a characteristic cell death reaction or else are severely inhibited in their growth. The biological significance of this phenomenon remains a puzzle. Heterokaryon incompatibility genes have been proposed to represent a vegetative self/nonself recognition system preventing heterokaryon formation between unlike individuals to limit horizontal transfer of cytoplasmic infectious elements. Molecular characterization of het genes and of genes participating in the incompatibility reaction has been achieved for two ascomycetes, Neurospora crassa and Podospora anserina. These analyses have shown that het genes are diverse in sequence and do not belong to a gene family and that at least some of them perform cellular functions in addition to their role in incompatibility. Divergence between the different allelic forms of a het gene is generally extensive, but single-amino-acid differences can be sufficient to trigger incompatibility. In some instances het gene evolution appears to be driven by positive selection, which suggests that the het genes indeed represent recognition systems. However, work on nonallelic incompatibility systems in P. anserina suggests that incompatibility might represent an accidental activation of a cellular system controlling adaptation to starvation.

丝状真菌可在个体内部以及个体之间自发发生营养细胞融合事件。这类细胞融合（又称菌丝融合，anastomoses）会引发细胞质混合，并形成营养异核体——即包含不同核类型的细胞。此类异核体的存活由特定基因座遗传调控，该基因座被称为异核体不亲和位点（het loci，为heterokaryon incompatibility的缩写）。当融合个体的het基因型存在差异时，所形成的异核体细胞会出现典型的细胞死亡反应，或其生长受到严重抑制。这一现象的生物学意义至今仍是一个未解之谜。有假说提出，异核体不亲和基因代表一类营养型自我/非自我识别系统，可阻止基因型相异的个体之间形成异核体，以此限制细胞质感染因子的水平转移。目前已在两种子囊菌——粗糙脉孢菌（Neurospora crassa）和鹅掌柄孢壳（Podospora anserina）中完成了het基因以及参与不亲和反应的基因的分子表征工作。分析结果表明，het基因序列多样性丰富，且不属于同一基因家族；其中至少部分基因除参与不亲和反应外，还兼具其他细胞功能。het基因的不同等位形式之间通常存在广泛的序列差异，但单个氨基酸的差异便足以触发不亲和反应。在部分案例中，het基因的演化似乎由正选择驱动，这表明het基因确实属于识别系统。然而，针对鹅掌柄孢壳中非等位不亲和系统的研究显示，不亲和反应可能只是调控饥饿适应的细胞系统的意外激活。