用于靶向基因组编辑的定点核酸酶(SDN)是强大的新工具,可将精确的遗传变化引入植物。像常规杂交和诱导诱变等传统方法一样,基因组编辑旨在提高作物产量和营养。
下一代测序研究表明,农作物物种的整个基因组通常携带数百万个单核苷酸多态性以及许多拷贝数和结构变异。自发突变以每代每个位点约10-8至10-9的速率发生,而化学处理或电离辐射引起的变异导致更高的突变率。
图 1 比较不同育种策略导入番茄的每个基因组(单个)的SNP和插入缺失的平均数。数据代表在S.lycopersicum(Heinz 1706参考基因组)的基因组序列与已用于现代番茄品种育种的其他品种或野生近缘种之间的大约SNP数量。
在SDN中,脱靶更改或编辑是发生在与目标编辑区域具有序列相似性的位点上的意外,非特异性突变。与自然发生在育种种群中或通过诱变方法引入的SDN变异相比,SDN介导的脱靶变异可以导致少量其他遗传变异。
最近的研究表明,使用计算算法设计基因组编辑试剂可以减轻植物的脱靶编辑。最后,农作物必须经过强有力的选择,才能通过成熟的多代育种,选择和商业品种开发实践来淘汰异型植物。
图2 来自前20个番茄育种国家的官方发布的突变品种数量,显示了用作育种材料的改良品种(橙条)和突变品种(蓝条)的直接释放。星号表示欧盟国家。数据来源:突变品种数据库(https://mvd.iaea.org).
在这种情况下,与其他育种实践相比,作物的脱靶编辑不会带来新的安全问题。已经证明,当前一代的基因组编辑技术对于开发具有消费者和农民利益的新植物品种很有用。
基因组编辑可能会伴随着SDN交付的新发展以及基因组表征的增加而提高编辑特异性,从而进一步改善试剂设计和应用。
Site-directed nucleases (SDNs) used for targeted genome editing are powerful new tools to introduce precise genetic changes into plants. Like traditional approaches, such as conventional crossing and induced mutagenesis, genome editing aims to improve crop yield and nutrition. Next-generation sequencing studies demonstrate that across their genomes, populations of crop species typically carry millions of single nucleotide polymorphisms and many copy number and structural variants. Spontaneous mutations occur at rates of ∼10−8 to 10−9 per site per generation, while variation induced by chemical treatment or ionizing radiation results in higher mutation rates. In the context of SDNs, an off-target change or edit is an unintended, nonspecific mutation occurring at a site with sequence similarity to the targeted edit region. SDN-mediated off-target changes can contribute to a small number of additional genetic variants compared to those that occur naturally in breeding populations or are introduced by induced-mutagenesis methods. Recent studies show that using computational algorithms to design genome editing reagents can mitigate off-target edits in plants. Finally, crops are subject to strong selection to eliminate off-type plants through well-established multigenerational breeding, selection, and commercial variety development practices. Within this context, off-target edits in crops present no new safety concerns compared to other breeding practices. The current generation of genome editing technologies is already proving useful to develop new plant varieties with consumer and farmer benefits. Genome editing will likely undergo improved editing specificity along with new developments in SDN delivery and increasing genomic characterization, further improving reagent design and application.
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