Ankfn1-mutant vestibular defects require loss of both ancestral and derived paralogs for penetrance in zebrafish.

How and to what degree gene duplication events create regulatory innovation, redundancy, or neofunctionalization remain important questions in animal evolution and comparative genetics. Ankfn1 genes are single copy in most invertebrates, partially duplicated in jawed vertebrates, and only the derived copy retained in most mammals. Null mutations in the single mouse homolog have vestibular and neurological abnormalities. Null mutation of the single Drosophila homolog is typically lethal with severe sensorimotor deficits in rare survivors. The functions and potential redundancy of paralogs in species with two copies are not known. Here, we define a vestibular role for Ankfn1 homologs in zebrafish based on the simultaneous disruption of each locus. Zebrafish with both paralogs disrupted showed vestibular defects and early lethality from swim bladder inflation failure. One intact copy at either locus was sufficient to prevent major phenotypes. Our results show that vertebrate Ankfn1 genes are required for vestibular-related functions, with at least partial redundancy between ancestral and derived paralogs.

基因复制事件如何以及在何种程度上产生调控创新、冗余或新功能化，仍然是动物进化和比较遗传学中的重要问题。Ankfn1基因在大多数无脊椎动物中是单拷贝的，在有颌脊椎动物中部分复制，并且在大多数哺乳动物中仅保留衍生拷贝。小鼠单个同源基因的无效突变会导致前庭和神经异常。果蝇单个同源基因的无效突变通常是致命的，极少数幸存者会出现严重的感觉运动缺陷。具有两个拷贝的物种中旁系同源基因的功能和潜在冗余性尚不清楚。在此，我们基于对每个基因座的同时破坏，确定了Ankfn1同源基因在斑马鱼中的前庭作用。两个旁系同源基因均被破坏的斑马鱼表现出前庭缺陷以及因鱼鳔充气失败导致的早期死亡。任一基因座上有一个完整拷贝足以防止主要表型出现。我们的结果表明，脊椎动物的Ankfn1基因是前庭相关功能所必需的，祖先旁系同源基因和衍生旁系同源基因之间至少存在部分冗余。