Original Research Results on Meiotic Recombination from SDU

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Meiosis is a specialized cellular program by which a diploid progenitor cell gives rise to haploid gametes (sperms and eggs). Crossover recombination, comprising the reciprocal exchange of DNA segments between paternal and maternal chromosomes, is the central feature of meiosis. Crossovers increase genetic diversity of species and ensure the proper meiotic chromosome segregation. Abnormally placed crossovers or absence of crossovers will lead to chromosome mis-segregation and thus aneuploidy. However, it is unclear how meiotic recombination is regulated and how species are benefit from crossovers.
In the issue ofCellpublished on March 14, Zhang Liangran and Wang Shunxin, Laboratories from Center for Reproductive Medicine, Shandong University, collaborating mainly with Nancy Kleckner laboratory from Harvard University, reveal a fundamental, evolutionarily conserved feature of meiosis: within individual meiotic nuclei, crossover frequencies covary across different chromosomes, and demonstrate its evolutionarily adaptive advantage. (Shunxin Wang,Carl Veller, Fei Sun, Aurora Ruiz-Herrera, Yongliang Shang, Hongbin Liu, Denise Zickler, Zijiang Chen, Nancy Kleckner and Liangran Zhang; Per-Nucleus Crossover Covariation and Implications for Evolution,Cell, 2019, 177: https://doi.org/10.1016/j.cell.2019.02.021).

Previous studies of crossovers mainly focus on analyzing crossover patterns on a single chromosome level, and revealed the existence of crossover, the phenomenon of crossover interference, in which crossovers tend to be evenly spaced along each chromosome. In this paper, Wang et al. analyzed crossovers on each chromosome in several eukaryotes including human and revealed a new basic feature of meiotic recombination that the numbers of crossovers across different chromosomes tend to covary within single nuclei. By further analysis, the basis for this effect is per-nucleus covariation of individual chromosome axis lengths which is determined by the covariation of chromatin loop length. The per-nucleus crossover covariation leads to overdispersed distribution of the numbers of total crossovers per nucleus, thus increases the frequencies of meiotic cells and thereafter gametes which have very many or very few crossovers. Population genetic modeling demonstrates the advantage of crossover covariation in fluctuating environment. When the environment changes, hyper-crossover gametes would be available to produce more new genetic combinations for adaptation. When environment is stable, hypo-crossover gametes would be available to maintain the parental well-evolved combinations.
These findings provide new insights into the mechanisms of the regulation of meiotic crossovers and its critical roles in evolutionary adaption.

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