Mutation accumulation in transfer RNAs: molecular evidence for Muller's ratchet in mitochondrial genomes

The accumulation of deleterious mutations is thought to be a major factor preventing the long-term persistence of obligately asexual lineages relative to their sexual ancestors. This phenomenon is also of potential relevance to sexual species that harbor asexually propagating organelle genomes. A comparative study of the transfer RNA genes in animal mitochondrial and nuclear genomes demonstrates that the former accumulate nucleotide substitutions much more rapidly than do the latter, and several lines of evidence are consistent with the idea that the excess substitutions are mildly deleterious. First, the average binding stability between complementary strands in the stems of mitochondrial tRNAs is less than half that in nuclear tRNAs. Second, most loop sizes in the mitochondrial tRNAs have experienced a net reduction in size over evolutionary time, and they are nearly 50 times more variable in the mitochondrial than in the nuclear genome. Third, although nearly 20% of the nucleotides in nuclear tRNA genes (particularly those involved in tertiary interactions) are invariant across all animal taxa and all tRNA species, there are no invariant sites in the mitochondrial tRNAs. These observations, as well as results from recent laboratory experiments, are consistent with the hypothesis that nonrecombining organelle genomes are subject to gradual loss of fitness due to the cumulative chance fixation of mildly deleterious mutations.      

基于进化足迹法结合位置打分函数的转录因子结合位点预测

目的:预测转录因子结合位点。方法:本文从ABS数据库上下载了人类和啮齿类动物的直系同源的启动子序列,首先使用位置打分函数对这些启动子序列进行打分,找到候选的转录因子结合位点,并进一步利用进化足迹法对这些候选的转录因子结合位点进行筛选,只有结合位点同时出现在人类和啮齿类动物的启动子序列才认为是真正的结合位点。结果:在对人类和啮齿类动物进行转录因子结合位点预测时,与单独使用打分函数的结果相比,进化足迹法与打分函数结合的方法有效的提高了预测结果的性能,大幅度提供所得预测结果的特异性。结论:进化足迹法结合位置打分矩阵的方法能较为准确有效的预测转录因子结合位点。     

Patterns in spontaneous mutation revealed by human-baboon sequence comparison

We have analyzed the alignment of a long homologous region of the human and baboon genomes (approximately 1.5 Mb). We show that the frequency of gaps between aligned segments decreases slowly with gap length, indicating that several successive nucleotides are often deleted or inserted in one event. By contrast, runs of consecutive mismatches decrease rapidly in frequency with increasing length, following an exponential distribution, indicating that nucleotides are mostly substituted one at a time. Nucleotide substitutions are clumped at the scales of <10 and 1000-10,000 nucleotides, but show almost no aggregation at the scales of <10-100 and over approximately 50,000 nucleotides. Apparently, two rather different factors make the substitution rate not exactly uniform along the DNA sequence. Comparison of regions of very similar genomes that are approximately selectively neutral makes it possible to study spontaneous mutation at a new level of resolution.