Gene Expression and Regulation
AP Biology Topic 6 8:40 English narration · English + 中文 subtitles burned in
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Transcript
That white thread in the tube is real DNA, pulled out of ordinary cells.
试管里那团白色的丝，是真正的DNA，从普通细胞里提取出来的。
It looks like nothing at all.
它看起来平平无奇。
But it holds every instruction your body will ever need.
可是它保存着你身体一生所需要的全部指令。
And here is the strange part: every cell in you carries the same set.
奇怪的地方在于：你体内的每一个细胞， 携带的都是同一套指令。
Why is a muscle cell not a nerve cell?
肌肉细胞为什么不是神经细胞呢？
Because a cell does not use every gene. It chooses.
因为细胞并不会使用每一个基因，它会做选择。
Today: how DNA is stored, copied, read into RNA, and built into protein — then how a cell switches genes on and off, and what happens when the code changes.
今天要讲：DNA如何储存、复制、被读成RNA、再造出蛋白质； 然后是细胞如何开关基因，以及密码改变时会发生什么。
Start with the molecule.
先看这个分子。
DNA is two strands of nucleotides twisted into a double helix — each nucleotide a sugar, a phosphate and a base, with the backbone outside and the bases as the rungs.
DNA是两条链拧成的双螺旋——外侧是糖和磷酸构成的骨架， 横档是成对的碱基。
Complementary base pairing is fixed: A with T, C with G.
配对是固定的：A配T，C配G。
Two hydrogen bonds for A and T, three for C and G.
A和T之间两个氢键，C和G之间三个。
And look at the ends: one strand runs five prime to three prime, the other runs the opposite way.
再看两端：一条链从五端到三端，另一条方向正好相反。
They are antiparallel.
它们是反平行的。
Where is that DNA kept?
这些DNA放在哪里？
A bacterium keeps one circular chromosome, plus small extra rings called plasmids.
细菌只有一条环状染色体，另外还有一些额外的小环，叫质粒。
A plant or animal cell is different: several long, straight chromosomes wound around proteins called histones, inside a nucleus.
植物或动物细胞不一样：有好几条又长又直的染色体，缠在叫组蛋白的蛋白质上， 装在细胞核里。
One more rule.
还有一条规则要记。
A and G are purines, with two rings.
A和G是嘌呤，有两个环。
C, T and U are pyrimidines, with one ring.
C、T和U是嘧啶，只有一个环。
A purine always pairs with a pyrimidine.
嘌呤总是和嘧啶配对。
Before a cell divides, it must copy all of it.
细胞分裂之前，必须把它全部复制一遍。
The two strands unzip, and free bases pair onto each old strand — A with T, C with G.
两条链解开， 游离的碱基分别配到每条旧链上——A配T，C配G。
At the end there are two molecules, and they are identical.
结束时得到两个分子，而且完全相同。
Look closely: each one keeps one old strand and one new strand — DNA replicates semiconservatively.
仔细看：每一个都保留了一条旧链和一条新链。 这就是半保留复制的意思。
Here is the machinery.
这是它的机器。
Helicase unzips the helix, and topoisomerase relaxes the twist ahead of it.
解旋酶把双螺旋解开，拓扑异构酶松开前方的扭结。
DNA polymerase builds the new strand, but only in one direction, five prime to three prime, and it needs a short RNA primer to start.
DNA聚合酶接着合成新链，但只能朝一个方向，从五端到三端， 而且需要一小段RNA引物才能起步。
So one strand runs smoothly — the leading strand.
所以一条链是一口气连续做出来的——前导链。
The other is built backwards in short pieces, which ligase joins.
另一条是倒着做成一小段一小段，再由连接酶接起来。
That is the lagging strand.
那就是后随链。
Copying is only storage.
复制只是保存。
To use a gene, the information has to flow.
要用一个基因，信息必须流动起来。
Watch.
看。
The DNA is copied into messenger RNA — that is transcription.
DNA先被抄成信使RNA——这就是转录。
Then a ribosome reads the RNA three bases at a time and joins amino acids into a chain — that is translation.
然后核糖体每次读三个碱基， 把氨基酸连成一条链——这就是翻译。
DNA to RNA to protein: the central dogma.
DNA到RNA，再到蛋白质：这就是中心法则。
RNA polymerase opens the DNA and copies only one strand — the template.
RNA聚合酶把DNA打开，只抄其中一条链——模板链。
Wherever the template says A, the RNA gets uracil, U, instead of T.
模板上是A的地方，RNA上用U，而不是T。
In a plant or animal cell the RNA must be processed before it leaves: a cap goes on one end, a long tail on the other, and the introns are cut out so only the exons remain.
在植物或动物细胞里，这条RNA还没完成： 一端加上帽子，另一端加上一条长尾巴，再把内含子剪掉，只留下外显子。
Join the exons differently, and one gene can make several proteins.
外显子换一种接法，同一个基因就能造出好几种蛋白质。
Three kinds of RNA, three different jobs.
三种RNA，三件不同的事。
Messenger RNA is the copy of the gene; it carries the message out to the ribosome.
信使RNA是基因的拷贝，它把信息带到核糖体。
Transfer RNA is the delivery van; one end holds an amino acid, the other end has three bases called an anticodon.
转运RNA是送货车：一端拿着一个氨基酸，另一端有三个碱基，叫反密码子。
Ribosomal RNA is the machine itself — the part of the ribosome that joins the amino acids.
核糖体RNA就是机器本身——核糖体上把氨基酸连起来的那一部分。
Now translation.
现在看翻译。
The ribosome reads the message three bases at a time, and each group of three is a codon.
核糖体每次读三个碱基，每三个一组就是一个密码子。
One codon names one amino acid.
一个密码子指定一个氨基酸。
Reading starts at the codon A, U, G, which also means methionine, and stops at one of three stop codons.
阅读从A、U、G这个密码子开始，它同时表示甲硫氨酸； 在三个终止密码子之一处停下。
Almost every living thing uses the same code — evidence of one common ancestor.
地球上几乎所有生物用的都是同一套密码——这说明我们有共同祖先。
Let's do a real question.
我们来做一道真实的考题。
A template strand of DNA reads T, A, C, then G, G, A, then T, T, C.
一条DNA模板链读作T、A、C，然后G、G、A，然后T、T、C。
Write the messenger RNA, and name the first three amino acids.
写出信使RNA，并说出前三个氨基酸。
Pause here and try it yourself.
先暂停，自己试一试。 准备好了吗？
Ready? First, pair every base, and remember RNA uses U in place of T.
首先，把每个碱基配对，记住RNA用U代替T。
T gives A, A gives U, C gives G.
T给出A，A给出U，C给出G。
So the message reads A, U, G, then C, C, U, then A, A, G. Now cut the message into codons and look them up.
所以这段信息读作A、U、G，然后C、C、U，然后A、A、G。
So the protein starts with methionine, then proline, then lysine — Met, Pro, Lys.
现在把信息切成密码子，再去查表。
And notice that most amino acids have more than one codon: the code is degenerate.
于是这个蛋白质开头是甲硫氨酸， 然后是脯氨酸，然后是赖氨酸。
Which genes does a cell actually use?
细胞到底用哪些基因？
Bacteria answer with an operon — a group of genes under one switch.
细菌用操纵子来解决——一组基因由同一个开关控制。
With no lactose, a repressor protein sits on the operator and blocks the way, so no enzymes are made.
没有乳糖时，阻遏蛋白坐在操纵基因上挡住去路，酶就造不出来。
Add lactose: it pulls the repressor off, the genes are transcribed, and the enzymes appear.
加入乳糖：它把阻遏蛋白拉下来，基因被转录，酶就出现了。
The cell builds the tool only when the job arrives.
有活儿来了，细胞才造工具。
Plant and animal cells use more layers.
植物和动物细胞的做法层次更多。
Transcription factors bind at the promoter, or at an enhancer further away, and switch transcription on or off.
转录因子结合在启动子上， 也可能结合在更远的增强子上，把转录打开或关掉。
Genes that share the same factors turn on together.
共用同一批因子的基因会一起开启。
Then there is epigenetics: adding methyl groups to DNA can silence a gene without changing a single base, and it can be undone.
还有表观遗传：给DNA加上甲基基团，可以让一个基因沉默， 而一个碱基都没有改变，而且它是可逆的。
Now we can answer our opening question.
现在我们可以回答开头那个问题了。
A stem cell can become a red blood cell, a muscle cell, or a nerve cell.
一个干细胞可以变成红细胞、肌肉细胞或神经细胞。
Every one keeps the same complete DNA — nothing is thrown away.
它们每一个保留的都是同样完整的DNA——没有丢掉任何东西。
What differs is which genes are switched on.
不同的只是哪些基因被打开。
That is differential gene expression, and it is how one fertilised egg builds a whole body.
这就是差异基因表达， 一个受精卵就是这样造出一整个身体的。
A mutation is any change in the DNA sequence.
突变就是DNA序列的任何改变。
Swap one base and you get a substitution.
把一个碱基换掉，就得到替换。
Sometimes nothing happens, because several codons name the same amino acid — silent.
有时什么也没发生，因为好几个密码子指的是同一个氨基酸——这叫沉默突变。
Sometimes one amino acid changes — missense.
有时一个氨基酸变了——错义突变。
Sometimes an early stop appears — nonsense.
有时出现提前的终止密码子——无义突变。
Now the last two rows: take a base out, or push one in, and every codon after it is read wrong.
再看最后两行：去掉一个碱基，或者塞进一个碱基，从那里往后每个密码子都读错了。
That is a frameshift.
这就是移码突变。
Is a mutation bad?
突变是坏事吗？
A mutation can be harmful, neutral, or beneficial, and the DNA alone will not tell you which.
突变可以是有害的、中性的，也可以是有益的， 而且光看DNA是判断不出来的。
It depends on the environment.
这取决于生物所处的环境。
Take sickle cell.
以镰状细胞为例。
One base changes, so one amino acid in haemoglobin changes.
一个碱基改变，血红蛋白里的一个氨基酸也跟着改变。
In most places that is harmful — but where malaria is common, one copy protects you.
在大多数地方这是有害的—— 但在疟疾流行的地区，带一个拷贝反而能保护你。
Mutations are random, and they are the only source of new variation.
突变是随机的，而且它们是新变异唯一的来源。
Last, the tools.
最后是工具。
The polymerase chain reaction copies a gene over and over.
聚合酶链式反应能把一个基因反复复制。
Three temperatures, repeated.
它只是三个温度，不断重复。
At ninety-five degrees the hydrogen bonds break and the strands separate.
九十五摄氏度，氢键断开，两条链分离。
At fifty-five, primers stick to each end of the target.
五十五摄氏度，引物结合到目标片段两端。
At seventy-two, Taq polymerase builds new strands.
七十二摄氏度，Taq聚合酶合成新链。
Each cycle doubles the DNA, so thirty cycles give about a billion copies.
每一轮让DNA翻一倍，所以三十轮大约能得到十亿份拷贝。
Biotechnology uses these same tools. Restriction enzymes cut DNA at particular sequences, PCR copies it, and CRISPR edits a chosen sequence directly. Copying gives you a lot of DNA.
复制让你得到大量DNA。
Sorting it is a different job — gel electrophoresis.
把它们分开是另一件事——凝胶电泳。
The samples go into wells at one end of a jelly slab, and the current goes on.
样品加到一块果冻状凝胶一端的小孔里，然后通电。
DNA is negatively charged, so every fragment moves to the positive end.
DNA带负电， 所以每一个片段都向正极移动。
Short fragments slip through the mesh and travel furthest.
短片段容易穿过这张网，跑得最远。
Here is a real gel under ultraviolet light.
这是一块真实的凝胶，在紫外光下拍摄。
Each glowing band is one length of DNA, and comparing the patterns gives a DNA fingerprint.
每一条发光的带就是一种长度的DNA，比较这些图案，就得到DNA指纹。
Three marks students lose every year.
有三个分，学生年年都在丢。
First, transcribe from the template strand, and write U where the template has A.
第一，从模板链转录，模板上是A的地方就写U。
Second, cells never lose genes — a specialised cell has the whole genome and expresses part of it.
第二，细胞从来不会丢掉基因——特化的细胞拥有整个基因组，只是表达其中一部分。
Third, know what each mutation does: a substitution changes at most one amino acid, but an insertion or deletion shifts every codon after it.
第三，弄清每种突变的后果：替换最多只改变一个氨基酸， 而插入或缺失会让它后面的每一个密码子都错位。