HEIP1 is required for efficient meiotic crossover implementation and is conserved from plants to humans

Abstract

Crossovers (CO) shuffle genetic information and physically connect homologous chromosomal pairs, ensuring their balanced segregation during meiosis. COs arising from the major class I pathway require the activity of the well-conserved group of ZMM proteins, which, in conjunction with MLH1, facilitate the maturation of DNA recombination intermediates specifically into COs. The HEI10 Interacting Protein 1 (HEIP1) was identified in rice and proposed to be a new, plant-specific member of the ZMM group. Here, we establish and decipher the function of the Arabidopsis thaliana HEIP1 homolog in meiotic crossover formation and report its wide conservation in eukaryotes. We show that the loss of Arabidopsis HEIP1 elicits a marked reduction in meiotic COs and their redistribution toward chromosome ends. Epistasis analysis showed that AtHEIP1 acts specifically in the class I CO pathway. Further, we show that HEIP1 acts both prior to crossover designation, as the number of MLH1 foci is reduced in heip1 , and at the maturation step of MLH1-marked sites into COs. Despite the HEIP1 protein being predicted to be primarily unstructured and very divergent at the sequence level, we identified homologs of HEIP1 in an extensive range of eukaryotes, including mammals.

Enhanced recombination empowers the detection and mapping of Quantitative Trait Loci

“…COs were detected using a sliding window approach as described in Lian et al 28 . Sequence data were also used to identify potential aneuploids using relative coverage between chromosomes 29 , 30 .

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“…Despite the large increase in recombination, recq4ab figl1 hybrid mutants are fertile 23 , and we detected a very low frequency of aneuploid in their progeny (0/329 for the full hybrid, and 2/583 for the CSL populations), suggesting that the high crossover rate does not impair chromosome segregation. In contrast, even a relatively mild defect in ensuring at least one crossover per chromosome at meiosis results in the production of aneuploids in the next generation 22 , 29 , 30 . Further, the F2 populations did not show any phenotypic defects compared to the wild type, with similar mean and variation in diverse phenotypes related to growth, shape, color, or flowering time (Fig.…”

ASY3 has dosage-dependent diverse effects on meiotic crossover formation

“…COs are generated through the repair of programmed DNA double-strand breaks (DSBs) via either of two pathways catalyzed by distinct recombination machineries: one machinery depends on the group of meiosis-specific ZMM proteins (Zip1-4, MSH4-5, and Mer3 in Saccharomyces cerevisiae , SHOC1/Zip2, HEI10/Zip3, HEIP1, PTD/Spo16, ZIP4, MSH4-5, and MER3 in Arabidopsis thaliana ) that catalyzes class I COs, representing the major class of COs (85% to 90% in Arabidopsis , 70%-90% in rice, 75%-90% in maize); the other machinery relies on structure-specific nucleases, e.g., MUS81 and FANCD2 (a homolog of Fanconi Anemia Complementation Group D2) in Arabidopsis , and promotes the remaining, so-called class II COs, which are not limited by interference (Kurzbauer et al , 2017; Thangavel et al , 2023; Mercier et al , 2015; Zhang et al , 2014a; Singh et al , 2023; Li et al , 2018).…”