经济学人：祖母吸烟产生的影响可能会遗传至孙辈

时光无念

Think of your grandchildren!

想想你的孙辈吧！

ONE of biology’s hottest topics is epigenetics. The term itself covers a multitude of sins. Strictly speaking, it refers to the regulation of gene expression by the chemical modification of DNA, or of the histone proteins in which DNA is usually wrapped. This modification is either the addition of methyl groups (a carbon atom and three hydrogens) to the DNA or of acetyl groups (two carbons, three hydrogens and an oxygen) to the histones. Methylation switches genes off. Acetylation switches them on. Since, in a multicellular organism, different cells need different genes to be active, such regulation is vital.

当今生物学最热的话题之一是表观遗传学，这个术语本身就涵盖了许多宗罪。严格来说，表观遗传学研究的是DNA或含有DNA的组蛋白化学改性中的基因表达调控现象。这种改性或者是甲基（一个碳原子和三个氢原子所组成的基团）增至DNA中，或者是乙酰基（两个碳原子、三个氢原子和一个氧原子所组成的基团）增加到组蛋白中。甲基化作用关闭基因，乙酰化作用启动基因。由于在多细胞有机体中，不同的细胞需要借助不同的基因以激活自身，所以这种调控至关重要。

What has got a lot of people excited, though, is the idea that epigenetic switches might be transmitted down the generations. Some see this as contrary to Darwinism, since it would permit characteristics acquired during an organism’s lifetime to be passed on to its offspring, as suggested by a rival theory of evolution put forward by Jean-Baptiste Lamarck. This is an exaggeration. The DNA sequence itself is not being permanently altered. Even those epigenetic changes that are inherited seem to be subsequently reversible. But the idea that acquired characteristics can be inherited at all is still an important and novel one, and a worrying example of the phenomenon has been published this week in BioMed Central Medicine.

但令人兴奋的是，有观点认为，表观遗传现象中的基因表达调控功能有可能世代相传。有些人将之视为对达尔文学说的反证，因为这将允许有机体存活期间所获得的特征遗传给后代，正如法国著名生物学家让-巴蒂斯特•拉马克所提出的与进化论相对的学说。这种想法有些夸张了。基因序列不会一直变化，甚至那些表观遗传学意义上的变化遗传给下一代后，似乎仍然存在可逆性。但是，“因表观遗传现象所获得的特征完全可以遗传”的观点仍然新颖且重要。本周，BioMed Central Medicine刊出了一项研究，可例证这一现象，其结果令人担忧。

The study in question, by Virender Rehan of the Los Angeles Biomedical Research Institute, and his colleagues, was of the intergenerational effects of nicotine. It was done in rats, but a rat’s physiology is sufficiently similar to a human’s to suspect the same thing may be true in Homo sapiens. In a nutshell, Dr Rehan showed that if pregnant rats are exposed to nicotine, not only will their offspring develop the asthma induced by this drug, so will the offspring of those offspring.

该项研究是由洛杉矶生物医学研究所的Virender Rehan和他的同事们开展的，研究的是尼古丁的代际影响。研究人员虽然在大鼠身上进行实验，但因为大鼠的生理机能与人类十分相像，所以研究人员怀疑对于大鼠的研究结果可能同样适用于智人（现代人）。简而言之，Rehan博士想说明的是，如果大鼠怀孕时接触尼古丁，不仅下一代会因此患上哮喘，第三代也会深受其害。

Dr Rehan and his team injected their rats with nicotine when they were six days pregnant. (Rat pregnancies last 22 days.) They then allowed them to give birth and raised the pups to the age of three weeks, before some were examined. The rest were allowed to mature and breed, and their own offspring were similarly examined. There was, however, no further administration of nicotine.

Rehan博士和他的团队在大鼠怀孕的第六天（大鼠妊娠期为22天）为其注射尼古丁。大鼠的后代出生后，由母鼠养育三周。然后研究人员选取一部分后代进行检查，其余的第二代大鼠继续生长繁殖，最后研究人员对第三代大鼠进行类似的检验。但是，第二代大鼠在妊娠期间，不再被注射尼古丁。

The pups of the treated mothers had asthmatic lungs. The organs’ airways were constricted, and molecular analysis showed abnormally high levels of fibronectin and collagen—which would stiffen the lung tissue—and also high levels of receptor molecules for nicotine. That was expected, since the developing embryos were exposed to the nicotine when their mothers were treated. However, when the team did similar tests on the grand-offspring of the treated mothers, they got similar results. Those grand-offspring had not been exposed to nicotine.

检测发现，被注射尼古丁的母鼠所繁殖的第二代大鼠肺部有哮喘病变。大鼠肺部的气道处于收缩状态。经过分子分析发现，大鼠肺部的纤维连接蛋白和胶原蛋白含量异常升高，这将导致肺组织硬化；同时尼古丁受体分子增加。结果表明，母鼠被注射尼古丁后，其后代在胚胎发育时期就会受尼古丁的影响，这一结果正如预期。但是，当研究团队对第三代大鼠进行类似检查时，发现了同样的情况，即使这些第三代大鼠并没有接触尼古丁。

The cause of the grand-offsprings’ asthma, Dr Rehan believes, is epigenetic modification. Nicotine is not only affecting lung cells, but also affecting sex cells in ways that cause the lungs which ultimately develop from those cells to express their genes in the same abnormal ways.

Rehan博士认为，第三代大鼠的哮喘是表观遗传中的改性现象。尼古丁不仅侵袭肺部细胞，还会影响生殖细胞，使得生殖细胞在发育器官时，在肺部异常表达基因，导致新发育的肺部同样受到尼古丁的不良影响。

Exactly what those epigenetic changes are is hard to track down. The team have started looking, but could find no clear pattern except that one form of nicotine-induced acetylation, that of H3 histones (histones come in five varieties), could be blocked by a molecule called RGZ. This molecule is also known to protect lungs against the asthma-causing effects of nicotine. That suggests it is the acetylation of H3 histones rather than the methylation of DNA itself that is creating the effect.

表观遗传现象具体引起了哪种变化，目前难以获知。研究团队已经开始研究这一问题，但目前只研究出一种明确的模式：尼古丁会引起H3组蛋白（组蛋白有五种类型）的乙酰化，进而导致一种叫做RGZ的分子受到抑制，而目前已知RGZ分子可以保护肺脏，使其免受由尼古丁引起的哮喘。这表明由尼古丁引起的哮喘是源于H3组蛋白的乙酰化，而非DNA自身的甲基化作用。

Which crucial genes these histones surround remains obscure. Nor have the team yet found out whether the epigenetic effect they have discovered reaches further than grand-offspring. If it does, though, it suggests that epigenetics really might act like the biblical curse: that the sins of the fathers (or, in this case, the mothers) will be visited on the sons, even unto the third and fourth generations.

研究团队目前没有研究出这些受影响的组蛋白包含着哪些关键基因，也没有发现表观遗传的影响（即后生效应）是否会延续至第三代以下的后代。然而，如果有研究表明后生效应会世代相传的话，这就表明表观遗传现象真真是有如圣经上的诅咒：父辈（或者是母亲）的罪孽，会降罪至他们的下一代身上，甚至会延续至第三代或者第四代。

谢雯

额。。。。最好的办法，全国禁烟，哈哈。

薛双倩

科学真可怕！查得这么严，呵呵。