克里斯托弗·万吉克　官华宇

You are what you eat， the saying goes. And， according to two new genetic studies， you are what your mother， father， grandparents and great-grandparents ate， too.

Diet， be it poor or healthy， can so alter the nature of ones DNA that those changes can be passed on to the progeny1. While this much has been speculated for years， researchers in two independent studies have found ways in which this likely is happening.

The findings， which involve epigenetics2， may help explain the increased genetic risk that children face compared to their parents for diseases such as obesity and diabetes.

Epigenetics

Epigenetics refers to changes in gene expression from outside forces. Different from a mutation， epigenetic changes lie not in the DNA itself but rather in its surroundings—the enzymes and other chemicals that orchestrate how a DNA molecule unwinds3 its various sections to make proteins or even new cells.

Recent studies have shown how nutrition dramatically alters the health and appearance of otherwise identical mice. A group led by Randy Jirtle of Duke University demonstrated how mouse clones implanted as embryos in separate mothers will have radical differences in fur color， weight， and risk for chronic diseases depending on what that mother was fed during pregnancy.

That is， the nutrients or lack of thereof changed the DNA environment in such a way that the identical DNA in these mouse clones expressed itself in very different ways.

Of mice and humans

Building upon this Duke University work， a new study led by Torsten Pl?sch of University of Groningen， The Netherlands， delineated4 the numerous ways in which nutrition alters the epigenome of many animals， including adult humans. The paper has been submitted to the journal Biochimie with lead author Josep C. Jiménez-Chillarón of the Paediatric Hospital Sant Joan de Deu， in Spain.

The researchers said that the diet of human adults induces changes in all cells—even sperm and egg cells—and that these changes can be passed on to offspring.

Such effects on a single generation have been known： Children born to mothers during the Dutch famine at the end of WWII had susceptibilities to various diseases later in life， such as glucose intolerance and cardiovascular disease， depending on the timing and extent of the food shortage during pregnancy.

In 2010， Jiménez-Chillarón and his colleagues took this a step further and found that overfed male mouse pups5 developed the telltale6 signs of metabolic syndrome7—insulin resistance， obesity and glucose intolerance—and passed some of these traits to their offspring， which then developed elements of metabolic syndrome without overeating.

But what still is missing， Jiménez-Chillarón told LiveScience， is an understanding of how such information is remembered from generation to generation. Unlike a gene mutation， all of the epigenetic inputs to the DNA environment should be forgotten when a newly formed embryo begins to divide.

“The dogma is that during the process of meiosis [cell division]， all epigenetic marks are erased，” said Jiménez-Chillarón. “But our work， as well as [the work] from many others， suggests that this is not completely true. Although the majority of epigenetic marks is erased， some marks are spared for unknown reasons.”

Attack on the DNA

A second study， led in part by Ram B. Singh of the TsimTsoum Institute in Krakow， Poland， published in the Canadian Journal of Physiology and Pharmacology， examined nutrients that affect the chromatin8. The chromatin is like the chemical soup in which DNA operates.

Aside from creating epigenetic marks， Singhs group speculates that these nutrients also can cause mutations， both good and bad. But the evidence is still inconclusive.

Hints of this were reported in a 2011 paper in Nature by Stanford University scientists who found lingering， positive effects on longevity from nutrition on three generations of the C. elegans worm9.

“It is possible that eating more omega-3 fatty acids， choline， betaine， folic acid and vitamin B12， by mothers and fathers， possibly can alter chromatin state and mutations， as well as have beneficial effects… leading to birth of a ‘super baby with long life and [lower risk] of diabetes and metabolic syndrome，” Singh told LiveScience. “This is just a possibility， to be proven by more experiments.”

Both teams of scientists said that cells in an early state of development are more prone to epigenetic changes from nutrition than adult cells， hence the most notable changes are seen fetuses and infants.

Yet it may be only a matter of time， they added， until there is evidence of how we pass along to subsequent generations the consequences of our own nutritional habits.

俗語云：人如其食。而两项新的遗传学研究则表明：人亦如其父母、祖父母乃至曾祖父母所食。

所谓饮食，无论贫乏抑或健康，都能改变一个人DNA的性质，以至那些改变还能遗传给后代。多年来人们对此颇多猜测，目前，两项独立研究的研究者已经发现这种现象可能的运行机制。

这些涉及表观遗传学的发现或许能帮助解释为什么孩子面临罹患肥胖症、糖尿病等疾病的遗传风险会比父母高。

表观遗传学

表观遗传学研究的是外界作用造成的基因表达的改变。与突变不同的是，表观遗传学改变并不在DNA本身，而在它的周围环境——即协调组织DNA解开自身各个区段以合成蛋白质甚或新细胞的那些酶和其他化学物质。

最近的研究阐明了营养状况如何使本该完全一致的小鼠在健康及外观上发生惊人变化。杜克大学的兰迪·杰特带领的团队证明了在胚胎时期被植入不同母体的克隆小鼠会因母体在妊娠期间摄入不同饲料而在毛色、体重和慢性病风险方面产生巨大差异。

这正是因为某些营养物质的摄入或缺乏改变了DNA所处的环境，以致这些克隆小鼠完全一致的DNA 在表达上产生了显著差异。

小鼠与人类

在杜克大学这项研究的基础上，荷兰格罗宁根大学的托斯顿·普拉施牵头的一项新研究则阐述了营养改变多种动物（包括成年人类）表观遗传的多个方式。研究报告已提交《生物化学》杂志，第一作者为西班牙圣女贞德儿童医院的何塞普·C.希门尼斯-奇利亚龙。……