3月26日，PNAS在线发表加拿大多伦多大学生态与进化生物学系研究人员的研究论文，研究人员发现拥有低质量基因的个体可能产生遗传质量更低的后代——至少在果蝇身上是这样。
Nathaniel Sharp 和Aneil Agrawal通过研究黑腹果蝇（Drosophila melanogaster）评估了遗传突变如何积累，这是一种常用于实验模型的果蝇。在蝇类身上，基因位于三个主要的染色体上。为了操纵遗传质量，科研人员向这些果蝇的3号染色体引入了有害突变。作者然后观察了在缺少自然选择的情况下这些变化如何影响46代后代的2号染色体。与拥有高质量的3号染色体的果蝇相比，拥有低质量的3号染色体的果蝇的2号染色体的适应度衰退速度是前者的2到3倍，这提示基因质量不良增加了后代的突变率。
这项发现背后的机制尚不明确，但是作者提出修复DNA损伤的能力可能在后代中被削弱了。此前的研究已经确定了突变在抑郁症、癌症和在人类与其他物种的一系列其他健康问题上起关键作用。作者说，这项研究提示基因质量不良可能让这类健康问题复杂化并且导致能够伤害濒危种群的灾难性突变。（生物谷 bioon.com）
doi:10.1073/pnas.1118918109
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Evidence for elevated mutation rates in low-quality genotypes
Nathaniel P. Sharp，Aneil F. Agrawa
The deleterious mutation rate plays a key role in a number of important topics in biology, from mating system evolution to human health. Despite this broad significance, the nature and causes of variation in mutation rate are poorly understood, especially in multicellular organisms. We test whether genetic quality, the presence or absence of deleterious alleles, affects the mutation rate in Drosophila melanogaster by using a modified mutation accumulation approach. We find evidence that genotypes constructed to carry deleterious “treatment” alleles on one chromosome during mutation accumulation experience an elevated mutation rate on a different chromosome. Further, this elevation is correlated with the effect of the treatment alleles on phenotypic condition, measured as body mass. Treatment alleles that reduce mass by 10% cause a doubling in the rate of mutational decline. Our results show that mutation rates are sensitive to genetic stress, such that individuals with low-quality genotypes will produce offspring of even lower genetic quality, in a mutational positive feedback loop. This type of variation in mutation rate is expected to alter a variety of predictions based on mutation load theory and accelerate adaptation to new environments. Positive mutational feedback could affect human health by increasing the rate of germline mutation, and possibly somatic mutation, in individuals of poor health because of genetic or environmental stress.
