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基因是什么？
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A generation game
基因游戏
本文英文部分选自经济学人Science and Technology版块
The ramifications of a new type of gene
一种新型基因的分支
It can pass on acquired characteristics
可传递已获得的（后天的）特征
WHAT’S a gene? You might think biologists had worked that one out by now. But the question is more slippery than may at first appear. The conventional answer is something like, “a piece of DNA that encodes the structure of a particular protein”. Proteins so created run the body. Genes, meanwhile, are passed on in sperm and eggs to carry the whole process to the next generation.
什么是基因？你可能认为生物学家已经找到了问题的答案。但是，这个问题可能要比起初发问时更棘手。传统答案一般就像是“一段编码特定蛋白质结构的DNA”。正是这些蛋白质维持身体运行。与此同时，基因通过精子和卵子传给下一代。
None of this is false. But it is now clear that reality is more complex. Many genes, it transpires, do not encode proteins. Instead, they regulate which proteins are produced. These newly discovered genes are sources of small pieces of RNA, known as micro-RNAs. RNA is a molecule allied to DNA, and is produced when DNA is read by an enzyme called RNA polymerase. If the DNA is a protein-coding gene, the resulting RNA acts as a messenger, taking the protein’s plan to a place where proteins are made. Micro-RNAs regulate this process by binding to the messenger RNA, making it inactive. More micro-RNA means less of the protein in question, and vice versa.
这些都不是错误的。但是现在明确的是，现实更加复杂。据披露，很多基因不编码蛋白质。相反，他们控制产生的蛋白质。这些新发现的基因是小片RNA的来源，被称为微RNA。RNA是与DNA相似的分子，当DNA被称为RNA聚合酶的酶读取时产生。如果DNA是一种编码蛋白质的基因，那么产生的RNA可以充当信使，将蛋白质的雏形带到制造蛋白质的地方。微RNA通过与信使RNA结合来控制这一过程，使其失去活性。越多的微RNA意味着上述的蛋白质越少，反之亦然。
注：RNA
https://en.wikipedia.org/wiki/RNA
非编码RNA
https://baike.baidu.com/item/%E9%9D%9E%E7%BC%96%E7%A0%81RNA/10066623?fr=aladdin
Often, this regulation is in response to environmental stimuli such as stress. And sometimes, the responses acquired in this way seem to be passed down through the generations, in apparent defiance of conventional genetic theory. The best known example in people comes from the Netherlands, which suffered famine in 1944, at the end of the second world war. Children born of starved mothers were, as might be expected, smaller than usual. But the children of those children were also small. Experiments carried out on mice confirm these observations.
通常而言，这种调节是对环境刺激（譬如压力）的反应。有时，这种在特殊情况下，后天获得的反应似乎一代代的传递了下去，但这一说法明显违背了传统的基因学说。最著名的例证是在1994年-二战后期，荷兰人民经历了一场饥荒，像预料那样，饥饿的母亲生下来的小孩儿比正常要小，而且这些小孩的后代同样很小。在老鼠身上做的实验证实了这些说法。
Stress city
压力之地
In the case of mothers, it is now believed that this process, called intergenerational epigenesis, is caused by micro-RNAs from the parent getting into eggs as they form in a developing fetus. That makes sense. Eggs are large cells, with room to accommodate these extra molecules. But intergenerational epigenetic effects can pass down the male line as well. And how paternal micro-RNAs come to be in an egg is a mystery, for the sperm that would have to carry them there are tiny and have no spare room. Work by Jennifer Chan, a graduate student at the University of Pennsylvania, has, however, shed light on the process.
从妈妈的遗传角度而言，现在普遍的观点是，代际间渐成的这一过程是由微RNA造成的微RNA从父母身上转移到卵子中，并且是在发育的胚胎中形成的。这能说得通。卵子是大型的细胞，有足够的空间按容纳这些多余的分子。但是代际间渐成的效应也能够从父系一支遗传下来。父亲的微RNA是如何进入卵子的，这尚不清楚，因为携带微RNA的精子很小，而且没有多余的空间。然而，宾夕法尼亚大学的研究生珍妮弗陈（Jennifer Chan）的论文对这一过程进行了阐述。
1.Epigenesis https://en.wikipedia.org/wiki/Epigenesis_(biology)
后成说(也称渐成说)是关于胚胎发育的一种假说。认为无论卵细胞还是精子中都不存在生物体发育的雏形，生物体的各种组织和器官都是在个体发育过程中逐渐形成的。
2.MicroRNA (miRNA) 是一类由内源基因编码的长度约为22 个核苷酸的非编码单链RNA 分子，它们在动植物中参与转录后基因表达调控。
https://en.wikipedia.org/wiki/MicroRNA
Ms Chan’s solution was described on February 16th by her research supervisor, Tracy Bale of the University of Maryland, at the annual meeting of the American Association for the Advancement of Science (AAAS), in Austin, Texas. The crucial insight behind her study was that micro-RNAs need not actually get inside sperm cells as they form. They could equally well be attached to sperm just before sexual intercourse. Ms Chan therefore concentrated her attentions on part of the male genital tract called the epididymis. This is where sperm mature. Cells lining the epididymis constantly discharge small, fluid-filled, membrane-bound bubbles called vesicles. When Ms Chan, working with mice, looked in detail at these vesicles, she found that they contained lots of micro-RNAs.
2月16日，在德克萨斯奥斯汀，美国科学促进会（AAAS）年会上，马兰里大学的特雷西贝尔（珍妮弗陈的研究主管）对陈女士的研究方法进行了描述。在她研究的背后，最重要的闪光点是，微RNA并不需要进入精子细胞。在人们性行为之前，微RNA可以附着在精子上。因此，陈女士把注意力放在男性的睾丸（精子成熟的地方）的上。排在附睾中的细胞不断地释放出小的，粘稠的，带有薄膜的囊泡。当陈女士用一个小鼠做实验时，详细观察了那些囊泡，她发现这些囊泡含有很多微RNA。
That was interesting. But she then went on to do an experiment. Mice are easily stressed. Simply putting new objects into their living space is enough to induce significant changes in their levels of stress hormones. Stress a male in this way and his offspring (of either sex) will react less to stress than do the offspring of unstressed males. That looks like intergenerational epigenesis. It also makes evolutionary sense, since it calibrates a mouse’s stress response to the stressfulness of the environment—which is likely to be the same as that of its father. To prove that this intergenerational effect was caused by epididymal micro-RNAs, Ms Chan collected these molecules and injected them into fertilised mouse eggs. Those eggs, as she had hypothesised they would, grew into less-stress-reactive adults.
那是非常有趣的发现。于是，她继续往下做实验。老鼠很容易紧张。仅仅是把一些新物体放在它们生活的地方就足以引发应激激素水平的显著变化。以这种方式给公鼠加压，他的后代（无论是何性别）都比那些未受压力老鼠繁殖出的后代，具有更好的抗压能力，这就像代际渐成。这也符合进化的道理，因为它改变了老鼠对压力环境作出的反应。（后代很有可能产生父辈一样的反应）为了证明这种代际效应是由附睾的微RNA所引起的，陈女士收集了那些分子并且把它注射到受孕的母鼠卵子中。正如她假设的那样，其后代更具抗压能力。
This work is all in mice. But Dr Bale has now roped some men into the experiment, too—namely 25 male students who have provided regular semen samples in order that the micro-RNAs therein can be tracked and correlated with such stressful events as sitting exams. The results of this are yet to come in. But, with her mouse work alone, it looks as if Ms Chan has cracked an important part of the puzzle ofintergenerational epigenesis.
这项试验全是在老鼠身上完成的。但是，贝尔博士现在已经说服一些人加入到实验中，也就是25名男性学生，他们提供了定期的精液样本，以便能够追踪到其中的微RNA，并将这些压力事件与久坐考试联系起来。这一结果尚未得到证实。但是，单凭在老鼠身上的试验，她就好像已经破解了代际后生之谜的一个重要部分。
Response to stress is not, however, the only thing in which micro-RNAs are implicated. They are also suspected of involvement in schizophrenia and bipolar disorder. To investigate this, a second speaker at the AAAS meeting, Paul Kenny, of the Icahn School of Medicine, in New York, also turned to mice.
然而，对压力的应激反应并不是微RNA所涉及的唯一情形。它们也被怀疑参与精神分裂症和双相情感障碍。为了研究这个问题，纽约的伊坎医学院的保罗·肯尼(Paul Kenny)在AAAS会议上的第二个发言人也对老鼠进行了研究。
The root of Dr Kenny’s suspicion was the discovery, post mortem, in the brains of patients who had been suffering from these conditions, of elevated levels of three micro-RNAs, called MiR206, MiR132 and MiR133b. He and his colleague Molly Heyer therefore looked at the role of these micro-RNAs in regulating brain cells called parvalbumin interneurons, which are thought to be involved in schizophrenia.
肯尼博士怀疑的根源在于，在患有这些疾病的病人的大脑中，发现了三种微RNA(MiR206、MiR132和MiR133b)的水平升高。因此，他和他的同事莫莉·海耶(Molly Heyer)研究了这些微RNA在调节称为小清蛋白中间神经元的大脑细胞中的作用，这些神经元被认为与精神分裂症有关。
Picking one, MiR206, for closer examination, the two researchers created a mouse strain in which the gene for MiR206 was switched off in the parvalbumin interneurons. They then performed experiments to study the behaviour of these mice, assuming that switching the gene off might protect them against schizophrenia-like symptoms. Surprisingly, they found the opposite.
择取其中一个，如MiR206，进一步研究，两名研究人员关闭了小鼠小清蛋白中间神经元上的MiR206表达细胞，并对小鼠施加压力。然后，他们对这些老鼠的行为进行了实验研究，原以为关闭基因表达可以保护小鼠免于患类似精神分裂症的疾病症状的影响。但是令人吃惊的是，实验结果和预期结果大相径庭。
Their first experiment was to play the mice a sudden, loud noise. This will startle any creature, mouse or man. If the noise is preceded by a softer one, however, both humans and murines react far less when the loud noise comes. They are expecting it. But people with schizophrenia seem never to learn this expectation. And neither, to the researchers’ surprise, do mice with the MiR206 knockout.
第一个实验中，研究人员突然播放了一个刺耳的噪音，这些噪音足以另任何生物受惊，不管是老鼠还是人类。但若是先放一个较为轻柔的噪音，那么播放高分贝噪音时，人类或老鼠的反应幅度都会小上很多，因为心中对于噪音有了预期。但是患有精神分裂症的人似乎怎样都无法学会这种预期。而令实验人员惊异的是，MiR206缺失的小鼠也没有类似预期
The scary moment
惊悚时刻
For people, these observations are often explained by the fact that one symptom of schizophrenia is increased fear. And, in a second experiment, Dr Kenny and Dr Heyer showed, again contrary to expectation, that MiR206-knockouts were unusually fearful as well.
从人类的角度而言，这些观察经常可以解释为精神分裂症患者症状之一是恐惧的增加。然后，在第二个实验中，肯尼博士和 耶尔博士发现，又一次不同于实验人员的预测的结果，MiR206缺失的小鼠同样表现了不同寻常的恐惧。
The researchers used a box which contained two lights, each positioned above a lever. First, a light would blink on and go off. Then, after a delay, both lights would come on. That was the signal for the mouse to press a lever. If the lever the mouse pressed was the one not under the initial light, the animal received some food. Drs Kenny and Heyer found that the knocked-out mice collected less food than did normal ones. But this was not because they were making mistakes. If they pressed a lever, they picked the correct one as often as a normal mouse would. Instead, they were pressing any lever less often. That was because they spent most of their time hiding in the corners of the box opposite the wall with the lights and levers. Again, they seemed abnormally afraid.
研究者们用了一个装有两盏灯的盒子，每盏灯都由一个拉杆控制。首先，一盏灯会闪烁然后消失。随后，在短暂停止后，两盏灯同时亮起。那就是让小鼠按下拉杆的信号。如果小鼠按下的拉杆不是在初始那盏灯下的，它就会得到一些食物。肯尼博士和耶尔博士发现（MiR2016）缺失的老鼠比正常老鼠得到的食物更少，但这并不是因为他们犯了错。如果他们按下了拉杆，他们会和他们正常的同类一样选择正确的。而是因为他们很少按下任何拉杆。他们大部分时间都在灯和拉杆对墙的箱子角落里。他们似乎再次感到异常的害怕。
What all this means for the study of schizophrenia is unclear. It is possible that examination of the other two pertinent micro-RNAs may shed more light on the matter. More generally, though, both Dr Kenny’s work and Ms Chan’s are good examples of the fact that there is more to genes than was once believed.
这些实验在精神分裂症的研究中意味着什么，目前尚不清晰。通过另外两个相关微RNA的检测，可能对这一问题有更多的了解。然而，更通俗的说，肯尼博士和陈小姐的成果都是很好的例子，证明基因中的学问比我们曾经认识到的要更多。
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