Cell:玉米KINDR蛋白如何打破孟德尔式分离定律?

2023-05-18 23:00:13

随着遗传学和表观遗传学研究的深入，人们对很多非孟德尔式遗传现象有了更深入地理解和认识。减数分裂驱动是打破孟德尔分离定律的主要力量。黑腹果蝇中的分离变相因子（segregation distorter, SD）是一种非常典型的具有减数分裂驱动性质的特殊遗传因子，是新物种形成的遗传力量。在玉米中存在着与SD类似的减数分裂驱动因子——异常第10染色体Ab10（abnormal chromosome 10）。Ab10是正常染色体的突变体，能够促使某些名为knobs的异染色质区域转换成可移动的新着丝粒（neocentromere）。这些形成的新着丝粒在分裂期间似着丝粒一样可受纺锤体牵引而移动，导致染色体末端在分裂后期首先移动，并造成由于染色体或片段的随机分配而导致的优先分离（preferential segregation）现象。

研究人员利用遗传学方法系统研究了玉米异常第10染色体Ab10（abnormal chromosome 10）中一段未知功能的区域。该区域约有1Mb大小，含有至少8个串联重复排列的名为Kindr（Kinesin driver）的基因。Kindr基因的表观突变——主要表现为DNA甲基化水平的增加以及小干扰RNA的积累——是Ab10形成和减数分裂驱动消失的主要原因。KINDR蛋白在体外具有负端导向驱动作用，在体内可以特异性地结合到含有180bp重复序列的knobs区域。序列分析结果表明，Kindr基因源于Kinesin-14A家族，它造成了>500Mb的knobs重复序列的形成并影响着第10染色体上上千个基因的分离。

KINDR驱动蛋白激活新着丝粒（neocentromere）并激活减数分裂驱动和非孟德尔遗传的功能帮助我们更深入地理解了复杂的减数分裂驱动过程。

Cell, 5 April 2018

A Kinesin-14 Motor Activates Neocentromeres to Promote Meiotic Drive in Maize

Author

R. Kelly Dawe*, Elizabeth G. Lowry, Jonathan I. Gent……Alex E. Harkess, Amy L. Hodges, Evelyn N. Hiatt

*: Department of Plant Biology; Department of Genetics, University of Georgia, USA

Summary

Maize abnormal chromosome 10 (Ab10) encodes a classic example of true meiotic drive that converts heterochromatic regions called knobs into motile neocentromeres that are preferentially transmitted to egg cells. Here, we identify a cluster of eight genes on Ab10, called the Kinesin driver(Kindr) complex, that are required for both neocentromere motility and preferential transmission. Two meiotic drive mutants that lack neocentromere activity proved to be kindr epimutants with increased DNA methylation across the entire gene cluster. RNAi of Kindr induced a third epimutant and corresponding loss of meiotic drive. Kinesin gliding assays and immunolocalization revealed that KINDR is a functional minus-end-directed kinesin that localizes specifically to knobs containing 180 bp repeats. Sequence comparisons suggest that Kindr diverged from a Kinesin-14A ancestor ∼12 mya and has driven the accumulation of > 500 Mb of knob repeats and affected the segregation of thousands of genes linked to knobs on all 10 chromosomes.

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