Gene knockdown approaches using antisense oligo nucleotides or analogs such as siRNAs and morpholinos have been widely adopted to study gene functions although the off-target issue has been always a concern in these studies. On the other hand, classic genetic analysis relies on the availability of loss-of-function or gain-of-function mutants. The fast development of genome editing technologies such as TALEN and CRISPR/Cas9 has greatly facilitated the generation of null mutants for the functional studies of target genes in a variety of organisms such as zebrafish. Surprisingly, an unexpected discrepancy was observed between morphant phenotype and mutant phenotype for many genes in zebrafish, i.e., while the morphant often displays an obvious phenotype, the corresponding null mutant appears relatively normal or only exhibits a mild phenotype due to gene compensation. Two recent reports have partially answered this intriguing question by showing that a pre-mature termination codon and homologous sequence are required to elicit the gene compensation and the histone modifying complex COMPASS is involved in activating the expression of the compensatory genes. Here, I summarize these exciting new progress and try to redefine the concept of genetic compensation and gene compensation.

使用脱义寡核苷酸或类似物（如siRNA和吗啉代）的基因敲除方法已被广泛用于研究基因功能，尽管脱靶问题一直是这些研究中关注的问题。另一方面，经典的遗传分析依赖于功能丧失或功能获得突变体的可用性。基因组编辑技术（例如TALEN和CRISPR / Cas9）的快速发展极大地促进了空突变体的产生，用于在各种生物（例如斑马鱼）中对目标基因进行功能研究。令人惊讶的是，对于斑马鱼中的许多基因，在突变体表型和突变体表型之间观察到了意想不到的差异，即，尽管该突变体通常表现出明显的表型，相应的无效突变体由于基因补偿而显得相对正常或仅表现出轻度的表型。最近的两个报道通过显示需要提前终止密码子和同源序列来引发基因补偿，而组蛋白修饰复合物COMPASS参与激活补偿基因的表达，部分地回答了这个有趣的问题。在这里，我总结了这些令人振奋的新进展，并试图重新定义基因补偿和基因补偿的概念。