Why are some human disease-associated mutations fixed in mice?
Why are some human disease-associated mutations fixed in mice?
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DOI：
10.1016/j.tig.2003.10.002
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发表时间：
2003-12-01
影响因子：
11.4
通讯作者：
Zhang, JZ
中科院分区：
文献类型：
--
作者：
Gao, LZ;Zhang, JZ
最近的一项比较基因组分析显示，小鼠体内存在已知与人类疾病相关的核苷酸序列，但小鼠却表现正常。在本文中，我们提出并测试了几个假设，试图解释为什么这些明显有害的突变在小鼠体内固定下来。我们发现，除了一个案例外，与疾病相关的突变的固定发生在至少 100 万年前小家鼠和小家鼠分离之前，并且这种固定不能归因于近期小鼠繁殖历史中的奠基者效应。大约 80% 的病例涉及人类育龄前发生的疾病，并且由于针对晚发疾病的自然选择效率低下，这些替代不太可能被固定。我们的结论是，补偿突变假说仍然是对小鼠中大多数疾病突变固定的最可能的解释。
A recent comparative genomic analysis revealed the presence of nucleotide sequences in mouse that are known to be disease-associated in humans, yet the mouse appears normal. In this article we formulate and test several hypotheses in an attempt to explain why these apparently deleterious mutations become fixed in mice. We find that except for one case, the fixations of the disease-associated mutations occurred before the separation of Mus musculus and Mus spretus at least 1 million years ago and that the fixations are not attributable to a founder effect during the recent history of mouse breeding. About 80% of the cases involve diseases that occur before reproductive age in humans and these substitutions are unlikely to have been fixed because of the inefficiency of natural selection against late-onset diseases. We conclude that the compensatory mutation hypothesis remains the most probable explanation for the majority of the fixations of disease mutations in mice.