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1、unit 5 why genes arent destiny为什么基因不是命运the remote, snow-swept expanses of northern sweden are an unlikely place to begin a story about cutting-edge genetic science. the kingdoms northernmost county, norrbotten, is nearly free of human life; an average of just six people live in each square mile. and
2、 yet this tiny population can reveal a lot about how genes work in our everyday lives.1. 偏远,白雪皑皑的瑞典北部区域不像是一个关于最前沿的基因科学的故事开始的地方。北博滕是这片区域最北部的一个镇,那儿人烟稀少,每平方公里平均只有两人居住。然而如此稀少的人口却大大揭示了基因在我们日常生活中的作用。norrbotten is so isolated that in the 19th century, if the harvest was bad, people starved. the starving ye
3、ars were all the crueler for their unpredictability. for instance, 1800, 1812, 1821, 1836 and 1856 were years of total crop failure and extreme suffering. but in 1801, 1822, 1828, 1844 and 1863, the land spilled forth such abundance that the same people who had gone hungry in previous winters were a
4、ble to gorge themselves for months.2. 北博滕是如此的与世隔绝以至于在十九世纪时,如果收成不好,人们就只能挨饿。由于其不可预测,饥饿的年成便更加恐怖。例如,1800,1812,1821,1836 和1856都是颗粒无收,民不聊生的年份。但在1801,1822,1828,1844及1863年,土地产出了如此丰沛的粮食以至于头年挨饿的人们可以连续数月大吃特吃。in the 1980s, dr. lars olov bygren, a preventive-health specialist who is now at the prestigious karoli
5、nska institute in stockholm, began to wonder what long-term effects the feast and famine years might have had on children growing up in norrbotten in the 19th century and not just on them but on their kids and grandkids as well. so he drew a random sample of 99 individuals born in the overkalix pari
6、sh of norrbotten in 1905 and used historical records to trace their parents and grandparents back to birth. by analyzing meticulous agricultural records, bygren and two colleagues determined how much food had been available to the parents and grandparents when they were young.3. 拉尔夫 欧勒 拜格伦博士是一位预防医学专
7、家,现任职于声名显赫的位于斯德哥尔摩的卡罗林斯卡学院。从二十世纪八十年代起,他开始研究丰收和饥饿的年份对十九世纪的北博滕孩子的成长的长期影响-不仅这些孩子,还有这些孩子的孩子以及孙辈。他随机抽取了生于1905年的北博滕奥佛卡利克斯教区的99个孩子作为研究对象。通过历史记录,他追踪到了这些孩子的父母和祖父母的生平。通过仔细分析农业生产记录,拜格伦和两个同事能够计算出那些父母和祖父母年轻时的食物有多少。around the time he started collecting the data, bygren had become fascinated with research showing
8、that conditions in the womb could affect your health not only when you were a fetus but well into adulthood. in 1986, for example, the lancet published the first of two groundbreaking papers showing that if a pregnant woman ate poorly, her child would be at significantly higher than average risk for
9、 cardiovascular disease as an adult. bygren wondered whether that effect could start even before pregnancy: could parents experiences early in their lives somehow change the traits they passed to their offspring?4. 研究表明,子宫内的环境不仅对胎儿健康有影响,这种影响甚至能够持续到一个人的成年期。拜格伦对这一研究产生了极大的兴趣,他开始收集相关数据。例如,柳叶刀杂志在1986年首次发
10、表了两篇具有突破性意义的文章,文中称,如果一个怀孕的妇女营养不良,那么她的孩子在成年后患心血管疾病的风险将远高于平均水平。拜格伦想知道,这种影响是否在孕期前就开始了,即:父母早期的生活经历是否会改变他们遗传给下一代的特征?it was a heretical idea. after all, we have had a long-standing deal with biology: whatever choices we make during our lives might ruin our short-term memory or make us fat or hasten death,
11、 but they wont change our genes our actual dna. which meant that when we had kids of our own, the genetic slate would be wiped clean.5. 这在当时是一个异端邪说的想法。毕竟,我们在生物学上有一个长期存在的观念,即:无论我们在生活中做出怎样的选择,都只能毁坏我们的短期记忆,或者使我们发胖,或加速我们的死亡,但是那些选择将不会改变我们的基因我们的脱氧核糖核酸(dna)结构。也就是说,当我们有了我们自己的孩子,我们的基因表又能恢复如常。whats more, any
12、such effects of nurture (environment) on a species nature (genes) were not supposed to happen so quickly. charles darwin, whose on the origin of species celebrated its 150th anniversary in november, taught us that evolutionary changes take place over many generations and through millions of years of
13、 natural selection. but bygren and other scientists have now amassed historical evidence suggesting that powerful environmental conditions (near death from starvation, for instance) can somehow leave an imprint on the genetic material in eggs and sperm. these genetic imprints can short-circuit evolu
14、tion and pass along new traits in a single generation.6. 并且我们以为养育(环境)对一个物种的天性(基因)的任何影响都不可能这么快地体现出来。查尔斯 达尔文的物种起源到今年十一月已发表了150周年,它告诉我们渐进式变革的发生需要许多代人的时间并且是几百万年自然选择的结果。但是拜格伦和其他科学家现在已经积累了历史证据来证明,强大的环境因素(例如由于饥饿而濒临死亡)能够在卵子和精子的基因物质上留下痕迹。这些基因痕迹能暂时中断进化并在下一代人身上留下新的特征。for instance, bygrens research showed that
15、in overkalix, boys who enjoyed those rare overabundant winters kids who went from normal eating to gluttony in a single season produced sons and grandsons who lived shorter lives. far shorter: in the first paper bygren wrote about norrbotten, which was published in 2001 in the dutch journal acta bio
16、theoretica, he showed that the grandsons of overkalix boys who had overeaten died an average of six years earlier than the grandsons of those who had endured a poor harvest. once bygren and his team controlled for certain socioeconomic variations, the difference in longevity jumped to an astonishing
17、 32 years. later papers using different norrbotten cohorts also found significant drops in life span and discovered that they applied along the female line as well, meaning that the daughters and granddaughters of girls who had gone from normal to gluttonous diets also lived shorter lives. to put it
18、 simply, the data suggested that a single winter of overeating as a youngster could initiate a biological chain of events that would lead ones grandchildren to die decades earlier than their peers did. how could this be possible?7. 例如,拜格伦的研究表明,在奥佛卡利克斯教区,那些享受了过于丰盛的冬季的男孩(在同一季节中经历了从正常饮食到暴饮暴食的孩子),他们的子辈和
19、孙辈寿命比其他人更短。拜格伦第一篇关于北博滕的论文发表于2001年的荷兰期刊acta biotheoretica 上,在这篇文章中他提到,生活在奥佛卡利克斯教区的有过度饮食经历男孩的孙辈比经历了收成很差的男孩的孙辈平均寿命短六年。当拜格伦和他的研究小组控制了社会经济方面的其他变量,这一寿命差距就上升到令人震惊的32年。此后的论文研究了北博滕另一些孩子,结果同样发现了明显的寿命下降,并且这一结果也适用于女性,即经历了从正常饮食到暴饮暴食的女孩的子辈和孙辈寿命比其他人更短。简言之,数据显示一个过度饮食的冬季会启动一连串的生物连锁反应,其结果是,一个人的孙辈比其他人的孙辈的寿命短几十年。这是怎样发生
20、的呢?meet the epigenome认识表观基因组the answer lies beyond both nature and nurture. bygrens data along with those of many other scientists working separately over the past 20 years have given birth to a new science called epigenetics. at its most basic, epigenetics is the study of changes in gene activity t
21、hat do not involve alterations to the genetic code but still get passed down to at least one successive generation. these patterns of gene expression are governed by the cellular material the epigenome that sits on top of the genome, just outside it (hence the prefix epi-, which means above). it is
22、these epigenetic marks that tell your genes to switch on or off, to speak loudly or whisper. it is through epigenetic marks that environmental factors like diet, stress and prenatal nutrition can make an imprint on genes that is passed from one generation to the next.8. 答案不在天生和养育。拜格伦的研究数据以及过去20年间许多在
23、此领域做了独立研究的科学家们的成果催生了一门叫表观遗传学的新学科。究其根本,表观遗传学是一门研究基因活动中产生的变化的学科,这种变化虽不使基因码产生变异但还是会影响接下来的至少一代人。这种基因表达的模式由一种叫表观基因组的细胞物质控制,表观基因组在基因组之上,就在其表层(这一点我们从表观基因组这个单词的前缀就可得知)。正是这些表观遗传“标记”告诉你的基因打开或关闭,大声说话或低声细语。通过这些表观遗传标记,诸如饮食,压力和产前营养等环境因素能在基因上留下印记并传给接下来的一代人。epigenetics brings both good news and bad. bad news first:
24、 theres evidence that lifestyle choices like smoking and eating too much can change the epigenetic marks atop your dna in ways that cause the genes for obesity to express themselves too strongly and the genes for longevity to express themselves too weakly. we all know that you can truncate your own
25、life if you smoke or overeat, but its becoming clear that those same bad behaviors can also predispose your kids before they are even conceived to disease and early death.9. 表观遗传学研究给我们同时带来了好消息和坏消息。先说坏消息:抽烟和过度饮食等生活方式上的选择能通过一些方式改变你的脱氧核糖核酸上的表观遗传标记,例如,使肥胖基因过于强烈地表达或使长寿基因表达过于无力。我们都知道,如果你吸烟或饮食过量,你的寿命将缩短,但是
26、,现在我们了解到,这些坏习惯也能使你的孩子(甚至在他们出生前就注定要)生病或早亡。the good news: scientists are learning to manipulate epigenetic marks in the lab, which means they are developing drugs that treat illness simply by silencing bad genes and jump-starting good ones. in 2004 the food and drug administration (fda) approved an ep
27、igenetic drug for the first time. azacitidine is used to treat patients with myelodysplastic syndromes (usually abbreviated, a bit oddly, to mds), a group of rare and deadly blood malignancies. the drug uses epigenetic marks to dial down genes in blood precursor cells that have become overexpressed.
28、 according to celgene corp. the summit, n.j., company that makes azacitidine people given a diagnosis of serious mds live a median of two years on azacitidine; those taking conventional blood medications live just 15 months.10. 好消息是:科学家们正在实验室里学习操纵表观遗传标记,这意味着他们在研发能够通过使坏基因噤声和启动好基因的方式来治病的药物。2004年,美国食品与
29、药物监管局首次批准了一种表观遗传药物的上市。阿扎胞苷被用于治疗脊髓增生异常综合症患者(脊髓增生异常综合症是罕见而又致命的血液恶性肿瘤)。此药物利用表观遗传标记来抑制过度表达的血液前体细胞。据阿扎胞苷生产商的数据,在被诊断出患有严重脊髓增生异常综合症的患者当中,服用阿扎胞苷的患者能存活两年,而服用传统药物的人只能存活15个月。since 2004, the fda has approved three other epigenetic drugs that are thought to work at least in part by stimulating tumor-suppressor g
30、enes that disease has silenced. the great hope for ongoing epigenetic research is that with the flick of a biochemical switch, we could tell genes that play a role in many diseases including cancer, schizophrenia, autism, alzheimers, diabetes and many others to lie dormant. we could, at long last, h
31、ave a trump card to play against darwin.11. 自从2004年以来,美国食品与药物监管局已经批准了三种表观遗传药物的上市,这些药物被认为能在一定程度上刺激那些受疾病影响没有正常表达的肿瘤抑制基因。对于不断进行的表观遗传学研究,我们寄予重望,希望能轻扣生化开关,便能使那些在许多疾病中(如,癌症,精神分裂症,自闭症,老年痴呆症,糖尿病,等等)发挥作用的基因沉睡。这样,我们最终就能有一张打败达尔文的王牌。the funny thing is, scientists have known about epigenetic marks since at least
32、 the 1970s. but until the late 90s, epigenetic phenomena were regarded as a sideshow to the main event, dna. to be sure, epigenetic marks were always understood to be important: after all, a cell in your brain and a cell in your kidney contain the exact same dna, and scientists have long known that
33、nascent cells can differentiate only when crucial epigenetic processes turn on or turn off the right genes in utero.12. 有意思的是,科学家们自二十世纪七十年代以来就对表观遗传标记有所了解,但在二十世纪九十年代后期之前,表观遗传现象一直被当作是dna这一主要事件的小插曲。确切地说,表观遗传标记从来被认为是重要的,毕竟,你的脑细胞和你的肾脏细胞包含完全相同的dna,只有当至关重要的表观遗传程序在子宫里打开或关闭正确的基因,初生细胞才能辨别他们。more recently, however, researchers have begun to realize that epigenetics could also help explain certain scientific mysteries
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