Highly variable recessive lethal or nearly lethal mutation rates during germ-line development of male Drosophila melanogaster
Highly variable recessive lethal or nearly lethal mutation rates during germ-line development of male Drosophila melanogaster
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DOI：
10.1073/pnas.1100233108
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发表时间：
2011-09-20
影响因子：
11.1
通讯作者：
Fu, Yun-Xin
中科院分区：
文献类型：
--
作者：
Gao, Jian-Jun;Pan, Xue-Rong;Fu, Yun-Xin
高等生物成虫的每个细胞都是通过一系列分裂从受精卵中产生的，在此期间可能发生突变。突变的速率和时间都可能对个体和群体产生深远的影响，因为在早期细胞分裂时发生的突变将影响更多的组织，并且更有可能转移到下一代。利用大规模的多代筛选实验和最近发展起来的统计分析，我们发现雄性果蝇的隐性致死或近致死突变。（一）突变率（ii）第一次细胞分裂具有最高的突变率，其在第二次分裂或接下来的几次分裂中大幅下降;（iii）中间阶段，在几次分裂之后到精子发生之前，具有至少一个数量级的较小突变率;精子发生也有较高的突变率。因为生殖细胞系与体细胞系共享一些（早期）细胞分裂，所以第一个结论很容易扩展到体细胞系。可以想象，第一个结论对大多数（如果不是全部的话）高等生物是正确的，而其他三个结论则广泛适用，尽管程度可能因物种而异。因此，基于发育过程中相同突变率的结论或分析应谨慎对待。此外，所开发的统计方法可用于研究其他生物体，包括人类生殖系或体细胞突变模式。
Each cell of higher organism adults is derived from a fertilized egg through a series of divisions, during which mutations can occur. Both the rate and timing of mutations can have profound impacts on both the individual and the population, because mutations that occur at early cell divisions will affect more tissues and are more likely to be transferred to the next generation. Using large-scale multigeneration screening experiments for recessive lethal or nearly lethal mutations of Drosophila melanogaster and recently developed statistical analysis, we show for male D. melanogaster that (i) mutation rates (for recessive lethal or nearly lethal) are highly variable during germ cell development; (ii) first cell cleavage has the highest mutation rate, which drops substantially in the second cleavage or the next few cleavages; (iii) the intermediate stages, after a few cleavages to right before spermatogenesis, have at least an order of magnitude smaller mutation rate; and (iv) spermatogenesis also harbors a fairly high mutation rate. Because germ-line lineage shares some (early) cell divisions with somatic cell lineage, the first conclusion is readily extended to a somatic cell lineage. It is conceivable that the first conclusion is true for most (if not all) higher organisms, whereas the other three conclusions are widely applicable, although the extent may differ from species to species. Therefore, conclusions or analyses that are based on equal mutation rates during development should be taken with caution. Furthermore, the statistical approach developed can be adopted for studying other organisms, including the human germ-line or somatic mutational patterns.