High Rate of Large Deletions in Caenorhabditis briggsae Mitochondrial Genome Mutation Processes
High Rate of Large Deletions in Caenorhabditis briggsae Mitochondrial Genome Mutation Processes
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DOI：
10.1093/gbe/evp055
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发表时间：
2010-01-01
影响因子：
3.3
通讯作者：
Denver, Dee R.
中科院分区：
文献类型：
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作者：
Howe, Dana K.;Baer, Charles F.;Denver, Dee R.
线粒体 DNA (mtDNA) 突变是多种人类遗传疾病的基础，并且与衰老过程相关。线粒体DNA多态性广泛应用于各种进化应用中。尽管众所周知，mtDNA 突变谱在亲缘关系较远的模式生物之间存在差异，但 mtDNA 突变过程在更密切相关的物种之间以及物种内部的差异程度仍然是个谜。我们分析了两组 250 代 Caenorhabditis briggsae 突变累积 (MA) 系的 mtDNA 差异，每个系均源自不同的天然分离祖细胞：来自日本冈山的 HK104 菌株和来自美国俄亥俄州的 PB800 菌株。两组 C. briggsae MA 系都积累了许多大的异质性 mtDNA 缺失，而在之前对秀丽隐杆线虫 MA 系 mtDNA 的分析中只观察到一个类似的事件。同聚物长度变化突变在两组 C. briggsae MA 系中都很常见，并且发生在基因间和蛋白质编码基因区域。 C. briggsae mtDNA 碱基取代突变谱与之前在秀丽隐杆线虫中观察到的谱不同。在 C. briggsae 中，HK104 MA 系经历了许多不同的碱基取代类型，而 PB800 系仅显示 C:G -> T:A 转变，尽管差异并不显着。在 C. briggsae MA 系中检测到的 mtDNA 碱基替换中有一半以上处于异质状态，而之前在 C. elegans MA 系 mtDNA 中鉴定的所有碱基替换都是固定变化，表明与 C. briggsae 相比，C. elegans 的 mtDNA 瓶颈更窄。我们的结果表明，C. briggsae mtDNA 对大的缺失非常敏感，并且不同线虫物种之间的线粒体突变过程有所不同。
Mitochondrial DNA (mtDNA) mutations underlie a variety of human genetic disorders and are associated with the aging process. mtDNA polymorphisms are widely used in a variety of evolutionary applications. Although mtDNA mutation spectra are known to differ between distantly related model organisms, the extent to which mtDNA mutation processes vary between more closely related species and within species remains enigmatic. We analyzed mtDNA divergence in two sets of 250-generation Caenorhabditis briggsae mutation-accumulation (MA) lines, each derived from a different natural isolate progenitor: strain HK104 from Okayama, Japan, and strain PB800 from Ohio, United States. Both sets of C. briggsae MA lines accumulated numerous large heteroplasmic mtDNA deletions, whereas only one similar event was observed in a previous analysis of Caenorhabditis elegans MA line mtDNA. Homopolymer length change mutations were frequent in both sets of C. briggsae MA lines and occurred in both intergenic and protein-coding gene regions. The spectrum of C. briggsae mtDNA base substitution mutations differed from the spectrum previously observed in C. elegans. In C. briggsae, the HK104 MA lines experienced many different base substitution types, whereas the PB800 lines displayed only C:G -> T:A transitions, although the difference was not significant. Over half of the mtDNA base substitutions detected in the C. briggsae MA lines were in a heteroplasmic state, whereas all those previously characterized in C. elegans MA line mtDNA were fixed changes, indicating a narrower mtDNA bottleneck in C. elegans as compared with C. briggsae. Our results show that C. briggsae mtDNA is highly susceptible to large deletions and that the mitochondrial mutation process varies between Caenorhabditis nematode species.