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什么是表冠遗传学? – 译学馆
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什么是表冠遗传学?

What is epigenetics? - Carlos Guerrero-Bosagna

这里有一个谜题:
Here’s a conundrum:
同一双胞胎源于相同的DNA
identical twins originate from the same DNA,
那么为什么他们会出现巨大的差异?
so how can they turn out so different
即使他们拥有一样的基因组成特征
even in traits that have a significant genetic component?
举个例子 为什么双胞胎中的一个可能在55岁时患上心脏病
For instance, why might one twin get heart disease at 55,
然而她的姐姐却以十分健康的状态跑完马拉松?
while her sister runs marathons in perfect health?
先天和后天有很多关系
Nature versus nurture has a lot to do with it,
但是更深层的答案可以在表观遗传学中找到
but a deeper related answer can be found within something called epigenetics.
这是一门科学 关于DNA如何
That’s the study of how DNA interacts
同大量在细胞中的微小分子相互作用
with the multitude of smaller molecules found within cells,
这个过程可以激活或隐藏基因
which can activate and deactivate genes.
如果你把DNA想象成为一本食谱书
If you think of DNA as a recipe book,
这些分子是决定什么时候煮什么的主要因素
those molecules are largely what determine what gets cooked when.
它们自身并没有做出任何有意识的决定
They aren’t making any conscious choices themselves,
但是它们在细胞内的存在和集中让一切都不同了
rather their presence and concentration within cells makes the difference.
所以一切是怎么发生的呢?
So how does that work?
当基因从DNA中读取和转录到RNA时会发生挤压
Genes in DNA are expressed when they’re read and transcribed into RNA,
通过结构向蛋白质转化
which is translated into proteins by structures called ribosomes.
成为核糖体并且蛋白质很大程度上决定了一个细胞的特性和功能
And proteins are much of what determines a cell’s characteristics and function.
表观遗传变异会促进或妨碍特定基因的转移
Epigenetic changes can boost or interfere with the transcription of specific genes.
最普遍的干扰方式发生在当DNA
The most common way interference happens is that DNA,
或者蛋白质在被缠绕
or the proteins it’s wrapped around,
得到化学标记时
gets labeled with small chemical tags.
所有的化学标记都依附于染色体组
The set of all of the chemical tags that are attached to the genome
属于一个特定的细胞
of a given cell
被称作是表观基因组
is called the epigenome.
它们其中的一些 像甲基 抑制基因的表达
Some of these, like a methyl group, inhibit gene expression
通过阻碍细胞的转录
by derailing the cellular transcription machinery
或导致DNA的盘绕更紧密
or causing the DNA to coil more tightly,
使得它们难以看到
making it inaccessible.
基因依旧存在
The gene is still there, but it’s silent.
但是沉默的促进转录有重要的反作用
Boosting transcription is essentially the opposite.
一些化学标记将展开DNA 让它们更加容易被转录
Some chemical tags will unwind the DNA, making it easier to transcribe,
这会加强相关蛋白质的生产
which ramps up production of the associated protein.
表观遗传变异能够使细胞分裂继续
Epigenetic changes can survive cell division,
这意味着它们能够影响一个有机体的全部生命周期
which means they could affect an organism for its entire life.
有的时候这是一件好事
Sometimes that’s a good thing.
表观遗传变异是正常成长的一部分
Epigenetic changes are part of normal development.
细胞是一个胚胎从一个主要的染色体组开始
The cells in an embryo start with one master genome.
当细胞开始分裂 一些基因被激活
As the cells divide, some genes are activated
其他的被抑制
and others inhibited.
一段时间后 通过表观遗传学的重新运作
Over time, through this epigenetic reprogramming,
一些细胞成长为心脏细胞
some cells develop into heart cells,
其他的成为肝脏细胞
and others into liver cells.
大约有200细胞类型在你的身体里
Each of the approximately 200 cell types in your body
每一个细胞类型都有相同的染色体组
has essentially the same genome
但是拥有他们自己不同的表观基因组
but its own distinct epigenome.
表观基因组同样介导终生对话
The epigenome also mediates a lifelong dialogue
在基因和环境中
between genes and the environment.
让基因表现和隐藏的化学标记
The chemical tags that turn genes on and off
能够被很多因素影响
can be influenced by factors including diet,
包括节食与化学品接触
chemical exposure,
以及药物治疗
and medication.
表观基因变异的结果最终会导致疾病
The resulting epigenetic changes can eventually lead to disease,
举例而言 如果它们隐藏了基因中肿瘤抑制的蛋白质
if, for example, they turn off a gene that makes a tumor-suppressing protein.
环境诱导的表观基因变异是其中一个原因
Environmentally-induced epigenetic changes are part of the reason
为什么基因相同的双胞胎在长大以后拥有不同的人生
why genetically identical twins can grow up to have very different lives.
当双胞胎慢慢长大 它们的表观基因组不一样了
As twins get older, their epigenomes diverge,
影响了他们的寿命和他们受疾病的损害程度
affecting the way they age and their susceptibility to disease.
甚至社会经历也能够导致表观基因变异
Even social experiences can cause epigenetic changes.
在一个著名的实验中
In one famous experiment,
当母老鼠对它们的幼崽不够关心的情况下
when mother rats weren’t attentive enough to their pups,
幼崽体内帮助它们管理压力的基因甲基化
genes in the babies that helped them manage stress were methylated
并且隐藏了
and turned off.
而且在这一代中或许不会停止
And it might not stop with that generation.
当卵子和精子细胞形成时 大部分表观基因的痕迹会被抹去
Most epigenetic marks are erased when egg and sperm cells are formed.
但是现在研究者认为它们其中一些的特征会延续
But now researchers think that some of those imprints survive,
通过这些表观基因的特征遗传到下一代
passing those epigenetic traits on to the next generation.
你的母亲或者父亲作为孩子的经历
Your mother’s or your father’s experiences as a child,
或者成为成年人后的选择
or choices as adults,
事实上可能形成了你自己的表观基因组
could actually shape your own epigenome.
但是即使表观基因变异是令人不满的
But even though epigenetic changes are sticky,
它们不是永久的
they’re not necessarily permanent.
一个平衡的生活方式包括健康的饮食
A balanced lifestyle that includes a healthy diet,
锻炼
exercise,
和避免暴露于污染
and avoiding exposure to contaminants
从长远来看 能够创造一个健康的表观基因组
may in the long run create a healthy epigenome.
是一个激动的时候来学习一下了
It’s an exciting time to be studying this.
科学家刚刚开始理解
Scientists are just beginning to understand
表观基因学如何能够解释人类机体的发展和成长
how epigenetics could explain mechanisms of human development and aging,
以及癌症的起源
as well as the origins of cancer,
心脏病的起源
heart disease,
精神病的起源
mental illness,
上瘾
addiction,
以及很多其他情况
and many other conditions.
与此同时 新表观基因组编辑的技术正在将它变得更简单
Meanwhile, new genome editing techniques are making it much easier
来区分哪些表观基因变异对于健康和疾病有重要意义
to identify which epigenetic changes really matter for health and disease.
一旦知道我们的表观基因如何影响我们
Once we understand how our epigenome influences us,
我们就能够同样去影响它
we might be able to influence it, too.

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