克里斯托弗·萬吉克　官華宇

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。而兩項新的遺傳學研究則表明：人亦如其父母、祖父母乃至曾祖父母所食。

所謂飲食，無論貧乏抑或健康，都能改變一個人DNA的性質，以至那些改變還能遺傳給后代。多年來人們對此頗多猜測，目前，兩項獨立研究的研究者已經發(fā)現(xiàn)這種現(xiàn)象可能的運行機制。

這些涉及表觀遺傳學的發(fā)現(xiàn)或許能幫助解釋為什么孩子面臨罹患肥胖癥、糖尿病等疾病的遺傳風險會比父母高。

表觀遺傳學

表觀遺傳學研究的是外界作用造成的基因表達的改變。與突變不同的是，表觀遺傳學改變并不在DNA本身，而在它的周圍環(huán)境——即協(xié)調組織DNA解開自身各個區(qū)段以合成蛋白質甚或新細胞的那些酶和其他化學物質。

最近的研究闡明了營養(yǎng)狀況如何使本該完全一致的小鼠在健康及外觀上發(fā)生驚人變化。杜克大學的蘭迪·杰特帶領的團隊證明了在胚胎時期被植入不同母體的克隆小鼠會因母體在妊娠期間攝入不同飼料而在毛色、體重和慢性病風險方面產生巨大差異。

這正是因為某些營養(yǎng)物質的攝入或缺乏改變了DNA所處的環(huán)境，以致這些克隆小鼠完全一致的DNA 在表達上產生了顯著差異。

小鼠與人類

在杜克大學這項研究的基礎上，荷蘭格羅寧根大學的托斯頓·普拉施牽頭的一項新研究則闡述了營養(yǎng)改變多種動物（包括成年人類）表觀遺傳的多個方式。研究報告已提交《生物化學》雜志，第一作者為西班牙圣女貞德兒童醫(yī)院的何塞普·C.希門尼斯-奇利亞龍。

研究者稱，成人的飲食會誘發(fā)所有細胞的改變——甚至改變精子和卵子——而這些改變可能遺傳給后代。

這樣的影響在一代以內已經被證實：經歷了二戰(zhàn)末荷蘭饑荒時期的母親誕下的孩子長大后都容易罹患包括葡萄糖耐受不良和心血管疾病在內的多種疾病，概率大小取決于母親懷孕期間遭受食物短缺影響的時間節(jié)點和嚴重程度。

2010年，希門尼斯-奇利亞龍和他的同事進一步發(fā)現(xiàn)，過度喂食的雄性幼鼠表現(xiàn)出代謝綜合征的明顯跡象——包括胰島素耐受、肥胖癥和葡萄糖耐受不良，它們更把部分癥狀遺傳給了后代，致使下一代小鼠不過度進食也出現(xiàn)了代謝綜合征的相關癥狀。

不過，希門尼斯-奇利亞龍告訴科學鮮聞網，現(xiàn)在還沒有弄清楚的是，這些信息如何能夠在代際遺傳中保留下來。不像基因突變，在新胚胎開始細胞分裂時，對DNA環(huán)境的所有表觀遺傳學輸入應該都會丟失。

“在生物學法則里，所有的表觀遺傳標記都會在減數分裂（一種細胞分裂方式）期間被抹除，”希門尼斯-奇利亞龍說道，“但我們及其他很多人的研究都表明，這個法則并不是完全正確的。盡管大部分表觀遺傳標記被抹除，仍然有一些標記出于未知的原因得以保留?！?/p>

攻擊DNA

波蘭克拉科夫齊姆索姆研究所的拉姆·B.辛格參與領導的另一項研究在《加拿大生理學與藥理學雜志》上發(fā)表了研究成果，該研究檢測了影響染色質的營養(yǎng)物質。染色質就好比化學物質的大雜燴，DNA在其中發(fā)揮功能。

辛格的團隊推測，這些營養(yǎng)物質除了創(chuàng)造表觀遺傳標志，還會造成突變，其中有好有壞。但是，他們仍然缺乏決定性的證據。

2011年斯坦福大學的科學家發(fā)表在《自然》雜志上的一篇論文也提到了這一點。他們發(fā)現(xiàn)，營養(yǎng)對于秀麗隱桿線蟲壽命的積極影響綿延了足足三代。

“父母攝入更多ω-3脂肪酸、膽堿、甜菜堿、葉酸和維生素B12，或許能夠改變染色質的狀態(tài)和突變，同時還有多個益處……有利于誕下更長壽、糖尿病和代謝綜合征患病風險更低的‘超級寶貝，”辛格告訴科學鮮聞網，“但這只是一種可能，還需要更多的實驗來證明。”

兩個科學家團隊都表示，處于發(fā)育早期的細胞比起成熟細胞更容易在營養(yǎng)作用下發(fā)生表觀遺傳學改變，所以胎兒和嬰兒的改變最為顯著。

他們還補充說，有關我們自身營養(yǎng)習慣所致影響如何傳遞給后代的證據總會被找到，只是時間早晚的問題。

（譯者為“《英語世界》杯”翻譯大賽獲獎者）