The genetic and molecular basis of haploinsufficiency in flowering plants

• Published in: Trends in plant science 2024-01, Vol.29 (1), p.72-85
• Main Authors: Navarro-Quiles, Carla, Lup, Samuel Daniel, Muñoz-Nortes, Tamara, Candela, Héctor, Micol, José Luis
• Format: Article
• Language: English
• Subjects: dominance; functional redundancy; gene dosage; haploinsufficiency; plants
• ISSN: 1360-1385; 1878-4372
• DOI: 10.1016/j.tplants.2023.07.009

•A first step in studying the molecular nature of dominant mutations is distinguishing between loss- and gain-of-function mutations. Loss-of-function mutations in haploinsufficient loci are dominant to their wild-type alleles.•Haploinsufficient genes typically encode components of multimeric complexes or proteins that participate in highly connected nodes in regulatory or signaling pathways.•The expression levels of haploinsufficient genes in yeast and plants are tightly controlled and their reduced expression or overexpression affect fitness.•Haploinsufficiency in flowering plants is not always easy to notice, as they contain large gene families whose members are functionally redundant. Raising awareness of this phenomenon among plant researchers will increase the detection of haploinsufficiency in plants. In diploid organisms, haploinsufficiency can be defined as the requirement for more than one fully functional copy of a gene. In contrast to most genes, whose loss-of-function alleles are recessive, loss-of-function alleles of haploinsufficient genes are dominant. However, forward and reverse genetic screens are biased towards obtaining recessive, loss-of-function mutations, therefore, dominant mutations of all types are underrepresented in mutant collections. Despite this underrepresentation, haploinsufficient loci have intriguing implications for studies of genome evolution, gene dosage, stability of protein complexes, genetic redundancy, and gene expression. Here we review examples of haploinsufficiency in flowering plants and describe the underlying molecular mechanisms and evolutionary forces driving haploinsufficiency. Finally, we discuss the masking of haploinsufficiency by genetic redundancy, a widespread phenomenon among angiosperms. In diploid organisms, haploinsufficiency can be defined as the requirement for more than one fully functional copy of a gene. In contrast to most genes, whose loss-of-function alleles are recessive, loss-of-function alleles of haploinsufficient genes are dominant. However, forward and reverse genetic screens are biased towards obtaining recessive, loss-of-function mutations, therefore, dominant mutations of all types are underrepresented in mutant collections. Despite this underrepresentation, haploinsufficient loci have intriguing implications for studies of genome evolution, gene dosage, stability of protein complexes, genetic redundancy, and gene expression. Here we review examples of haploinsufficiency in flowe