母亲的线粒体DNA，会影响后代的身高、寿命和疾病风险
剑桥大学对35万人进行的一项研究表明，线粒体——为我们的细胞提供能量的“电池”——在常见疾病(如2型糖尿病和多发性硬化症)中发挥着意想不到的作用。
The study, published today in Nature Genetics, found that genetic variants in the DNA of mitochondria could increase the risk of developing these conditions, as well influencing characteristics such as height and lifespan.
这项研究发表在今天的《自然·遗传学》(Nature Genetics)杂志上，研究发现：线粒体DNA的基因变异，可能会增加患这些疾病的风险，并影响身高和寿命等特征。
There was also evidence that some changes in mitochondrial DNA were more common in people with Scottish, Welsh or Northumbrian genetic ancestry, implying that mitochondrial DNA and nuclear DNA (which accounts for 99.9% of our genetic make-up) interact with each other.
也有证据表明，线粒体DNA的一些变化在苏格兰、威尔士或诺森伯兰遗传祖先中更常见，这意味着线粒体DNA和核DNA(占我们基因组成的99.9%)相互作用。
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Almost all of the DNA that makes up the human genome—the body's 'blueprint' - is contained within the nuclei of our cells. Among other functions, nuclear DNA codes for the characteristics that make us individual as well as for the proteins that do most of the work in our bodies.
几乎所有构成人类基因组的DNA——人体的“蓝图”——都包含在细胞核中。在其他功能中，核DNA编码使我们成为个体的特征，以及完成我们身体大部分工作的蛋白质。
Our cells also contain mitochondria, often referred to as 'batteries', which provide the energy for our cells to function. They do this by converting the food that we eat into ATP, a molecule capable of releasing energy very quickly. Each of these mitochondria is coded for by a tiny amount of 'mitochondrial DNA'. Mitochondrial DNA makes up only 0.1% of the overall human genome and is passed down exclusively from mother to child.
我们的细胞也含有线粒体，它为我们的细胞提供运行所需的能量。它们通过将我们吃的食物转化为ATP来达到这一目的，ATP是一种能够快速释放能量的分子。每一个线粒体都由少量的“线粒体DNA”编码。线粒体DNA只占人类基因总数的0.1%，而且只从母亲遗传给孩子。
While errors in mitochondrial DNA can lead to so-called mitochondrial diseases, which can be severely disabling, until now there had been little evidence that these variants can influence more common diseases. Several small-scale studies have hinted at this possibility, but scientists have been unable to replicate their findings.
虽然线粒体DNA的错误，可能会导致所谓的线粒体疾病，从而导致严重的残疾，但到目前为止，几乎没有证据表明这些变异会影响更常见的疾病。一些小规模的研究，已经暗示了这种可能性，但科学家们一直无法复制他们的发现。
Now, a team at the University of Cambridge has developed a new technique to study mitochondrial DNA and its relation to human diseases and characteristics in samples taken from 358,000 volunteers as part of UK Biobank, a large-scale biomedical database and research resource.
现在，剑桥大学(University of Cambridge)的一个研究小组开发了一种新技术，研究取自358000名志愿者样本的线粒体DNA及其与人类疾病和特征的关系。这些样本是英国生物样本库(UK Biobank)的一部分。
Dr. Joanna Howson, who carried out the work while at the Department of Public Health and Primary Care at the University of Cambridge, said: "Using this new method, we've been able to look for associations between the numerous features that have been recorded for participants of UK Biobank and see whether any correlate with mitochondrial DNA.
剑桥大学公共卫生和初级护理学系的乔安娜·豪森(Joanna Howson)博士表示：“使用这种新方法，我们已经能够寻找关联的众多特性，记录了参与者之间的英国生物库，看是否与线粒体DNA相关联。”
"Aside from mitochondrial diseases, we don't generally associate mitochondrial DNA variants with common diseases. But what we've shown is that mitochondrial DNA—which we inherit from our mother—influences the risk of some diseases such as type 2 diabetes and MS as well as a number of common characteristics."
“除了线粒体疾病，我们通常不会将线粒体DNA变异与常见疾病联系起来。但我们已经证明，人类从母亲那里继承的线粒体DNA会影响一些疾病的风险，如2型糖尿病和多发性硬化，以及一些共同特征。”
Among those factors found to be influenced by mitochondrial DNA are: type 2 diabetes, multiple sclerosis, liver and kidney function, blood count parameters, life span and height. While some of the effects are seen more extremely in patients with rare inherited mitochondrial diseases—for example, patients with severe disease are often shorter than average—the effect in healthy individuals tends to be much subtler, likely accounting for just a few millimetres' height difference, for example.
在这些被发现受线粒体DNA影响的因素中有：2型糖尿病、多发性硬化症、肝肾功能、血细胞计数参数、寿命和身高。虽然有些影响在患有罕见遗传性线粒体疾病的患者身上表现得更为明显——例如，患有严重疾病的患者往往比平均身高要短——但在健康个体身上的影响往往要微妙得多，例如，可能只有几毫米的身高差异。
There are several possible explanations for how mitochondrial DNA exerts its influence. One is that changes to mitochondrial DNA lead to subtle differences in our ability to produce energy. However, it is likely to be more complicated, affecting complex biological pathways inside our bodies—the signals that allow our cells to operate in a coordinated fashion.
线粒体疾病目前没有治愈方法。对于线粒体DNA如何发挥其影响，有几种可能的解释。一是线粒体DNA的改变，导致我们产生能量的能力发生细微的变化。然而，它可能更复杂，影响我们体内复杂的生物途径——让我们的细胞以协调的方式运作的信号。
Professor Patrick Chinnery from the MRC Mitochondrial Biology Unit at Cambridge said: "If you want a complete picture of common diseases, then clearly you're going to need to factor in the influence of mitochondrial DNA. The ultimate aim of studies of our DNA is to understand the mechanisms that underlie these diseases and find new ways to treat them. Our work could help identify potential new drug targets."
来自英国医学研究委员会线粒体生物学小组的Patrick Chinnery教授表示：“如果你想了解常见疾病的完整情况，那么显然你需要考虑线粒体DNA的影响。对我们DNA研究的最终目的是了解这些疾病背后的机制，并找到治疗它们的新方法。我们的工作可以帮助确定潜在的新药物靶点。”
Unlike nuclear DNA, which is passed down from both the mother and the father, mitochondria DNA is inherited exclusively from the mother. This suggests that the two systems are inherited independently and hence there should be no association between an individual's nuclear and mitochondrial DNA—however, this was not what the team found.
研究人员表明，特定的核遗传背景优先与特定的线粒体遗传背景相关，尤其是在苏格兰、威尔士和诺森比亚。这表明，我们的核基因组和线粒体基因组已经进化，并将继续进化，彼此相互作用。
The researchers showed that certain nuclear genetic backgrounds are associated preferentially with certain mitochondrial genetic backgrounds, particularly in Scotland, Wales and Northumbria. This suggests that our nuclear and mitochondrial genomes have evolved—and continue to evolve—side-by-side and interact with each other.
其中一个原因可能是兼容性的需要。ATP是由线粒体内一组称为呼吸链的蛋白质产生的。呼吸链有100多种成分，其中13种是由线粒体DNA编码的;其余的由核DNA编码。尽管呼吸链中的蛋白质是由两个不同的基因组产生的，但这些蛋白质需要像拼图一样在物理上相互连锁。
One reason that may explain this is the need for compatibility. ATP is produced by a group of proteins inside the mitochondria, called the respiratory chain. There are over 100 components of the respiratory chain, 13 of which are coded for by mitochondrial DNA; the remainder are coded for by nuclear DNA. Even though proteins in the respiratory chain are being produced by two different genomes, the proteins need to physically interlock like pieces of a jigsaw.
如果孩子遗传的线粒体DNA与父亲遗传的核DNA不相容，拼图就不能正确地组合在一起，从而影响呼吸链，进而影响能量生产。这可能会微妙地影响一个人的健康或生理，从进化的角度来看，随着时间的推移，这可能是不利的。相反，匹配会被进化所鼓励，因此变得更加普遍。
If the mitochondrial DNA inherited by a child was not compatible with the nuclear DNA inherited from the father, the jigsaw would not fit together properly, thereby affecting the respiratory chain and, consequently, energy production. This might subtly influence an individual's health or physiology, which over time could be disadvantageous from an evolutionary perspective. Conversely, matches would be encouraged by evolution and therefore become more common.
此前还有研究表明，DNA测序表明，年龄越大的母亲，自身细胞的线粒体DNA突变越多。而高龄母亲生育的孩子，也更易患线粒体疾病。
This could have implications for the success of mitochondrial transfer therapy—a new technique that enables scientists to replace a mother's defective mitochondria with those from a donor, thereby preventing her child from having a potentially life-threatening mitochondrial disease.
这可能意味着线粒体转移治疗的成功——一项新技术使科学家能够用捐赠者的线粒体替换母亲有缺陷的线粒体，从而防止她的孩子患有潜在的危及生命的线粒体引发的疾病。
