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(xiàng)新的遺傳學(xué)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(gè)人DNA的性質(zhì)，以至那些改變還能遺傳給后代。多年來人們對(duì)此頗多猜測(cè)，目前，兩項(xiàng)獨(dú)立研究的研究者已經(jīng)發(fā)現(xiàn)這種現(xiàn)象可能的運(yùn)行機(jī)制。

這些涉及表觀遺傳學(xué)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(fēng)險(xiǎn)會(huì)比父母高。

表觀遺傳學(xué)

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

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(xué)的蘭迪·杰特帶領(lǐng)的團(tuán)隊(duì)證明了在胚胎時(shí)期被植入不同母體的克隆小鼠會(huì)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(fēng)險(xiǎn)方面產(chǎn)生巨大差異。

這正是因?yàn)槟承I養(yǎng)物質(zhì)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(dá)上產(chǎn)生了顯著差異。

小鼠與人類

在杜克大學(xué)這項(xiàng)研究的基礎(chǔ)上，荷蘭格羅寧根大學(xué)的托斯頓·普拉施牽頭的一項(xiàng)新研究則闡述了營養(yǎng)改變多種動(dòng)物（包括成年人類）表觀遺傳的多個(gè)方式。研究報(bào)告已提交《生物化學(xué)》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(huì)誘發(fā)所有細(xì)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(nèi)已經(jīng)被證實(shí)：經(jīng)歷了二戰(zhàn)末荷蘭饑荒時(shí)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(nèi)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(shí)間節(jié)點(diǎn)和嚴(yán)重程度。

2010年，希門尼斯-奇利亞龍和他的同事進(jìn)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(jìn)食也出現(xiàn)了代謝綜合征的相關(guān)癥狀。

不過，希門尼斯-奇利亞龍告訴科學(xué)鮮聞網(wǎng)，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(xì)胞分裂時(shí)，對(duì)DNA環(huán)境的所有表觀遺傳學(xué)輸入應(yīng)該都會(huì)丟失。

“在生物學(xué)法則里，所有的表觀遺傳標(biāo)記都會(huì)在減數(shù)分裂（一種細(xì)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(gè)法則并不是完全正確的。盡管大部分表觀遺傳標(biāo)記被抹除，仍然有一些標(biāo)記出于未知的原因得以保留。”

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(lǐng)導(dǎo)的另一項(xiàng)研究在《加拿大生理學(xué)與藥理學(xué)雜志》上發(fā)表了研究成果，該研究檢測(cè)了影響染色質(zhì)的營養(yǎng)物質(zhì)。染色質(zhì)就好比化學(xué)物質(zhì)的大雜燴，DNA在其中發(fā)揮功能。

辛格的團(tuán)隊(duì)推測(cè)，這些營養(yǎng)物質(zhì)除了創(chuàng)造表觀遺傳標(biāo)志，還會(huì)造成突變，其中有好有壞。但是，他們?nèi)匀蝗狈Q定性的證據(jù)。

2011年斯坦福大學(xué)的科學(xué)家發(fā)表在《自然》雜志上的一篇論文也提到了這一點(diǎn)。他們發(fā)現(xiàn)，營養(yǎng)對(duì)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?nèi)旧|(zhì)的狀態(tài)和突變，同時(shí)還有多個(gè)益處……有利于誕下更長壽、糖尿病和代謝綜合征患病風(fēng)險(xiǎn)更低的‘超級(jí)寶貝，”辛格告訴科學(xué)鮮聞網(wǎng)，“但這只是一種可能，還需要更多的實(shí)驗(yàn)來證明?！?/p>

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

他們還補(bǔ)充說，有關(guān)我們自身營養(yǎng)習(xí)慣所致影響如何傳遞給后代的證據(jù)總會(huì)被找到，只是時(shí)間早晚的問題。

（譯者為“《英語世界》杯”翻譯大賽獲獎(jiǎng)?wù)撸?/p>