“The genetic and molecular basis of haploinsufficiency in plants”

   In diploid organisms, haploinsufficiency (HI) can be defined as the requirement of more than one fully functional copy of a gene, rendering apparent dominance to loss-of-function allele in haploinsufficient genes. However, forward and reverse genetic screens are biased toward obtaining recessive, loss-of-function mutations, and thus, 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.¹ Haploinsufficient genes typically encode components of multimeric complexes or proteins that participate in highly connected nodes in regulatory or signaling pathways. HI in flowering plants is not always easy to notice, because these plants contain large gene families whose members are functionally redundant. Combined haploinsufficiency arises when the combined heterozygosity of two or more genes produces a mutant phenotype, but single heterozygotes are phenotypically wild type. Conditional haploinsufficiency is when HI depends on environmental conditions.

Analyses of HI tend to divide its occurrences in four broad mechanistic categories  via (1) direct protein insufficiency, which has been described in terms of shortages of developmental regulators operating close to functional thresholds, such as transcription factors (TFs), (2) Stochastic effects, partly due to the finite number of partners involved in the transcription reaction per cell, that is one or two DNA alleles, low concentrations of TFs, and the concentration of RNA polymerase II in a finite number of transcription factories, (3) Rate-limiting enzymes, compares the retention of paralogues at evolutionary scale in each category of genes following whole genome duplication (WGD) events,(4) Subunit imbalance, concerning the assembly and functioning of multi-subunit complexes, such as occurs among many TFs.³

    HI in plants, has proved useful to improve agronomically relevant traits. In maize 27 and 50 kDa γ-zein genes, which are linked, share combined haploinsufficiency, wherein diheterozygous plants for a deleted copy of each gene render a kernel phenotype intermediate between those lines with high and low 27 and 50 kDa γ-zein contents, with improved nutritional quality⁴. Overdominance also occurs in tomato plants containing a hypomorphic single flower truss (sft) allele in combination with a wild-type allele². In heterozygous plants, the yield is up to 60% higher than in homozygous wild-type plants, suggesting haploinsufficiency as potential genetic mechanism driving overdominance.

              Despite the complexity of most haploinsufficient genes, it is evident that HI can drive heterosis in flowering plants. Further insight into the mechanisms driving HI is still needed; however, this phenomenon has proved useful for understanding complex molecular mechanisms, with possible applications for fine-tuned genetic breeding of crop species.

References:

1.   NAVARRO-QUILES, C., LUP, S. D., MUÑOZ-NORTES, T., CANDELA, H. AND MICOL, J.L., 2024, The genetic and molecular basis of haploinsufficiency in flowering plants. Trends Plant Sci., 29(1): 72-85.

2.   KRIEGER, U., 2010, The flowering gene SINGLE FLOWER TRUSS drives heterosis for yield in tomato. Nat. Genet., 42: 459–463.

3.   JOHNSON, A.F., NGUYEN, H. T. AND VEITIA, R.A., 2019, Causes and effects of haploinsufficiency. Biol. Rev., 94(5): 1774-1785.

YUAN, L., 2014, Deletion mutagenesis identifies a haploinsufficient role for γ-zein in opaque2 endosperm modification. Plant Physiol., 164: 119–130.