Unlike other organs, the thymus and gonads generate nonuniform cell populations, many members of which perish, and a few survive. While it is recognized that thymic cells are “audited” to optimize an organism’s immune repertoire, whether gametogenesis could be orchestrated similarly to favor high-quality gametes is uncertain. Ideally, such quality would be affirmed at early stages before the commitment of extensive parental resources. A case is here made that, along the lines of a previously proposed lymphocyte quality control mechanism, gamete quality can be registered indirectly through detection of incompatibilities between proteins encoded by the grandparental DNA sequences within the parent from which haploid gametes are meiotically derived. This “stress test” is achieved in the same way that thymic screening for potential immunological incompatibilities is achieved—by “promiscuous” expression, under the influence of the AIRE protein, of the products of genes that are not normally specific for that organ. Consistent with this, the Aire gene is expressed in both thymus and gonads, and AIRE deficiency impedes function in both organs. While not excluding the subsequent emergence of hybrid incompatibilities due to the intermixing of genomic sequences from parents (rather than grandparents), many observations, such as the number of proteins that are aberrantly expressed during gametogenesis, can be explained on this basis. Indeed, promiscuous expression could have first evolved in gamete-forming cells where incompatible proteins would be manifest as aberrant protein aggregates that cause apoptosis. This mechanism would later have been co-opted by thymic epithelial cells which display peptides from aggregates to remove potentially autoreactive T cells.

中文翻译：

---

当很少有人能讲这个故事时：作为试听器官的胸腺和性腺：历史概述。

与其他器官不同，胸腺和性腺会产生不均匀的细胞群，其中许多成员会死亡，少数会存活。尽管人们认识到胸腺细胞是“经过审计的”以优化生物体的免疫功能，但不确定是否可以类似地编排配子发生以支持优质配子。理想情况下，应在投入大量父母资源之前尽早确定这种质量。在此提出的一个案例是，沿着先前提出的淋巴细胞质量控制机制，配子质量可以通过检测由单倍体配子从其产生亲本的亲本中的祖父母DNA序列编码的蛋白质之间的不相容性来间接记录。这种“压力测试”的实现方式与通过胸腺细胞筛查潜在的免疫学不相容性的方式相同-通过在AIRE蛋白的影响下“杂乱”地表达通常对该器官没有特异性的基因产物。与此一致，Aire基因在胸腺和性腺中都有表达，AIRE缺乏会阻碍这两个器官的功能。虽然不排除随后由于来自父母（而不是祖父母）的基因组序列混合而出现杂种不相容性，但可以在此基础上解释许多观察结果，例如配子发生过程中异常表达的蛋白质数量。确实，混杂表达可能首先在配子形成细胞中进化，其中不相容的蛋白质将表现为引起凋亡的异常蛋白质聚集体。后来胸腺上皮细胞选择了这种机制，胸腺上皮细胞从聚集物中展示肽以去除潜在的自身反应性T细胞。