The recent advances and future perspectives of genetic compensation studies in the zebrafish model

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 compen-sation 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 compensa-tion 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 ad-dressing 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 poten-tial therapeutic strategy to treat human genetic disorder related diseases. 2022 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).

Automated summary

Genetic compensation is the ability of organisms to maintain their fitness and viability in the face of genetic mutation disruptions. The underlying mechanism of genetic compensation is still unresolved, but recent studies in zebrafish have uncovered that it can be triggered by the upregulation of compensating genes and involve collaboration with epigenetic machinery. The study of genetic compensation has potential implications for understanding gene function and developing therapeutic strategies for human genetic disorders.