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A team deciphers complicated mechanism underlying genetic diversity. Movies such as 'X-Men,' 'Fantastic Four,' and 'The Guardians,' which showcase vibrant mutant heroes, have captivated global audiences. Recently, a high-throughput genetic screening of meiotic crossover rate mutants in Arabidopsis thaliana garnered the interest of the academic community by unraveling a century-old mystery in the life sciences. A research team, consisting of Professor Kyuha Choi, Dr. Jaeil Kim, and PhD candidate Heejin Kim from the Department of Life Sciences at Pohang University of Science and Technology (POSTECH), has achieved a remarkable feat by unveiling the molecular mechanism responsible for crossover interference during meiosis, a biological pattern at the chromosome level. The findings of this research were published on February 20 in Nature Plants, an international journal in the field of life sciences. In sexually reproducing organisms, individuals resemble their parents or siblings. Despite the striking similarities, it's crucial to recognize that absolute identicalness is unattainable. This variation is attributed to the process of meiosis, which generates reproductive cells like sperm and eggs in animals or pollen and ovules in plants. Unlike somatic cell division, which duplicates and divides the genome identically, meiosis creates genetically diverse reproductive cells through a mechanism known as crossover. Meiosis and crossover play pivotal roles in biodiversity and have significant implications in breeding where the selection and cultivation of superior traits in crops occur. Typically, most animal and plant species exhibit a minimum of one and a maximum of three crossovers per a pair of homologous chromosomes. The ability to control the number of these crossovers could lead to cultivating crops with specific desired traits. However, achieving such control has been challenging due to the 'phenomenon of crossover interference.' Crossover interference, where one crossover inhibits the formation of another crossover nearby along the same chromosome, was initially identified by fruit fly geneticist Hermann J. Muller in 1916. Despite researchers' persistent efforts over the past century since its discovery, it is only recently that the mechanisms underlying crossover interference have started to unveil their secrets. In this research, the team utilized a high-throughput fluorescent seed scoring method to directly measure crossover frequency in Arabidopsis plants. Through a genetic screen, they identified a mutant named hcr3 (high crossover rate3) that exhibited an increased crossover rate at the genomic level. Further analysis revealed that the elevated crossovers in hcr3 was attributed to a point mutation in the J3 gene, which encodes a co-chaperone related to HSP40 protein. This research demonstrated that a network involving HCR3/J3/HSP40 co-chaperone and the chaperone HSP70 controls crossover interference and localization by facilitating the degradation of the pro-crossover protein, HEI10 ubiquitin E3 ligase. The application of genetic screen approaches to uncover the crossover interference and inhibition pathway successfully addressed a century-old puzzle in the life sciences. POSTECH Professor Kyuha Choi stated, "Applying this research to agriculture will enable us to rapidly accumulate beneficial traits, thereby reducing breeding time." He expressed optimism by saying, "We hope this research will contribute to the breeding of new varieties and identification of useful natural variations responsible for desirable traits such as disease and environmental stress resistance, improved productivity, and high-value production." The research was conducted with support from the Basic Research Program in Science and Engineering and the Mid-Career Researcher Program of the National Research Foundation of Korea, the Next-Generation BioGreen 21 Program of the Rural Development Administration, the Suh Kyungbae Foundation, and the Samsung Science & Technology Foundation.

New findings suggest an explanation for the century-old mystery of how chromosome recombination is regulated during sexual reproduction. In most higher organisms, including humans, every cell carries two versions of each gene, which are referred to as alleles. Each parent passes on one allele to each offspring. As they are linked together on chromosomes, adjacent genes are usually inherited together. However, this is not always the case. Why? The answer is recombination, a process that shuffles the allele content between homologous chromosomes during cell division. Mechanistically, recombination is achieved by crossovers, where homologous chromosomes contact each other, resulting in the exchange of genetic material. Crossovers have long fascinated scientists and especially plant breeders because manipulating the crossover process offers the potential of increasing genetic diversity and of assembling desired combinations of alleles that boost crop productivity. Crossovers are subject to a "Goldilocks principle"; at least one is required per chromosome pair for successful sexual reproduction; indeed, a lack of crossovers is a major cause of human trisomy such as in the case of Down's Syndrome. Crossover numbers are also tightly regulated and generally do not exceed three. This limit on crossover number, and therefore, recombination, is achieved by crossover interference, a phenomenon through which crossovers inhibit additional crossovers in their vicinity. However, how this interference works has remained a mystery since it was first described some 120 years ago. New model of crossover interference Now, a team led by Raphael Mercier at the Max Planck Institute for Plant Breeding Research in Cologne, Germany, have found convincing evidence in support of a recently proposed model of crossover interference. Mercier and his team, together with collaborators, in work spearheaded by Stéphanie Durand, Qichao Lian, and Juli Jing, achieved these insights by manipulating the expression of proteins known to be involved in either promoting crossovers or in connecting chromosomes together in the model plant Arabidopsis thaliana, a species which Mercier and his colleagues use to gain fundamental insights into the mechanisms of heredity. Boosting expression of the pro-crossover protein HEI10 resulted in a significant increase in crossovers, as did disrupting the expression of the protein ZYP1, a constituent of the synaptonemal complex, a protein structure that forms between homologous chromosomes. When the scientists combined the two interventions, they were surprised to observe a massive increase in crossovers, showing that HE10 dosage and ZYP1 jointly control CO patterning. Importantly, massively increasing crossovers in this way barely affected cell division. The considerable increase in crossovers upon increasing HEI10 levels chimes well with an emerging model for how crossover number is regulated. This model, formulated by David Zwicker and his team at the Max Planck Institute for Dynamics and Self-Organization in Göttingen, Germany, is based on diffusion of the HEI10 protein along the synaptonemal complex and a coarsening process leading to well-spaced HEI10 foci that promote crossovers. In the model, HEI10 initially forms multiple small foci and is progressively consolidated into a small number of large foci that co-localize with sites of crossovers. In this simple model, increasing the levels of HEI10 will result in more foci and therefore more crossovers; thus, the formation of droplets along an axis appears to be the determinant of crossover sites. Mercier is excited by the team's findings but is also already looking ahead: "These results are an exciting insight into a process that has baffled scientists for over a hundred years. Next, we want to better understand what controls the dynamics of the HEI10 droplets and how they promote crossovers. If we can get a better handle on how the process works, this may allow us selectively boost recombination during plant breeding, enabling the assembly of combinations of beneficial alleles that have remained out of reach."