Recently, the research group of Prof. Zhang Liangran from the School of Life Sciences and the State Key Laboratory of Microbial Technology (Shandong University), who has been selected for the “1000-talents Plan” for young researchers, made a breakthrough in the field of meiosis. The research paper “Inefficient Crossover Maturation Underlines Elevated Aneuploidy in Human Female Meiosis” was published online in the journal Cell on March 2.
Dr. Wang Shunxin, member of the group, is the first author of the paper, and Prof. Zhang and Harvard University professor Nancy Kleckner , member of the US National Academy of Sciences, are corresponding authors. It is the first time for Shandong University as both the first author and corresponding author’s institution to publish a research paper in the top level journal Cell.
Meiosis, an essential program for organisms producing the male and female gemmates, is tightly regulated with high fidelity. But human female meiosis is dramatically error-prone, a high frequency of eggs with aberrant set of chromosomes ("aneuploidy"), and the frequency of aneuploidies increases with increasing maternal age and can be up to 50% in women close to the end of reproductive lifespan. Aneuploidy eggs can cause sterility, and when fertilized the aneuploidy zygote can lead to infertility or develop to a child with genetic defects, among which the most known one is Down syndrome, which has 3 chromosome 21. But the reason of human female meiosis producing so high frequency of aneuploidy eggs is unclear.
Recently, Zhang's laboratory in Shandong University with his collaborators have investigated the meiotic crossover recombination, the crucial process of meiosis, in both human male and female. They have discovered that there is a crossover maturation defect specifically in female, but not in male, meiosis, which is called “female-specific crossover maturation inefficiency”. Because of this defect, ~25% crossover designations (crossover recombination intermediates) normally should give crossovers, but fail to do so. The consequence is that some homologous chromosome pairs failed to obtain the essential single crossover, and crossovers distributed abnormally along homologous chromosome pairs. Both of these effects can cause high frequency of chromosome segregation errors and thus high frequency of aneuploidies. Thus this “female-specific crossover maturation inefficiency” is the basis of the aneuploidies regardless of maternal age. Furthermore, this defect can work with other effects directly or indirectly to increase the aneuploidy level dramatically, especially in old women. These conclusions are further confirmed by quantitative modelling.
What is the biological significance of this defect? One possibility, as raised by previous studies, is that aneuploidy may confer an evolutionary advantage, e.g. increase the time between viable pregnancies to maintain enough maternal resources for young children, or, prevent a women to have a child before she is too old to raise a child. An alternative possibility is that human evolutionary time is still not long enough.
Professor Zhang joined in State Key Laboratory of Microbial Technology (Shandong University) in 2015 as a winner of 1000-talents Plan for young researchers. The research in Zhang's laboratory is focused on the mechanisms of meiosis. Professor Zhang has published a series of works in Nature, Cell, Genes & Development etc. This work was supported by NSFC, the 1000-talents Plan for young researchers, Qilu Scholar of Shandong University, and Shandong Provincial Natural Science Foundation.
Source: the School of Life Sciences, the State Key Laboratory of Microbial Technology (SDU)
Edited by: Xie Tingting