Abstract:
Genetic compensation is a remarkable biological concept to explain the genetic robustness in an organism to maintain its fitness and viability if there is a disruption occurred in the genetic variation by mutation. However, the underlying mechanism in genetic compensation remain unsolvable. The initial concept of genetic compensation has been studied in model organisms when there was a discrepancy between knockout-mediated and knockdown-mediated phenotypes. In the zebrafish model, several studies have reported that zebrafish mutants did not exhibit severe phenotype as shown in zebrafish morphants for the same genes. This phenomenon in zebrafish mutants but not morphants is due to the response of genetic compensation. In 2019, two amazing works partially uncovered genetic compensation could be triggered by the upregulation of compensating genes through regulating NMD and/or PTC-bearing mRNA in collaboration with epigenetic machinery in mutant zebrafish. In this review, we would like to update the recent advances and future perspectives of genetic compensation studies, which including the hypothesis of time-dependent involvement and addressing the discrepancy between knockout-mediated and knockdown-mediated to study gene function in the zebrafish model. At last, the study of genetic compensation could be a potential therapeutic strategy to treat human genetic disorder related diseases.
摘要:
遗传补偿是一个显着的生物学概念,可以解释生物体中的遗传稳健性,以维持其适应性和生存能力,如果通过突变在遗传变异中发生破坏。然而,遗传补偿的潜在机制仍然无法解决。当敲除介导的表型和敲除介导的表型之间存在差异时,已经在模型生物中研究了遗传补偿的初始概念。在斑马鱼模型中,一些研究报道,斑马鱼突变体没有表现出严重的表型,如斑马鱼的相同基因的形态。斑马鱼突变体而非突变体中的这种现象是由于遗传补偿的反应。2019年,通过调节NMD和/或携带PTC的mRNA,与突变斑马鱼的表观遗传机制合作,补偿基因的上调可能会引发两项部分揭示的基因补偿的惊人作品。在这次审查中,我们想更新基因补偿研究的最新进展和未来前景,其中包括时间依赖性参与的假设,并解决敲除介导和敲除介导之间的差异,以研究斑马鱼模型中的基因功能。最后,遗传补偿研究可能是治疗人类遗传病相关疾病的潜在治疗策略。