科學家正在學習改寫生命密碼（1/2）

Recently the New York Times reported the following:

Scientists Are Learning to Rewrite the Code of Life (1/2)

In a giant feat of genetic engineering, scientists have created bacteria that make proteins in a radically different way than all natural species do.

By Carl Zimmer - Origins (Carl Zimmer covers news about science for The Times and writes the Origins column.)

July 31, 2025

At the heart of all life is a code. Our cells use it to turn the information in our DNA into proteins. So do maple trees. So do hammerhead sharks. So do shiitake mushrooms. Except for some minor variations, the genetic code is universal.

It’s also redundant. DNA can code for the same building block of proteins in more than one way. Researchers have long debated what purpose this redundancy serves — or whether it’s just an accident of history.

Thanks to advances in genetic engineering, they can now do more than just argue. Over the past decade, scientists have built microbes with smaller codes that lack some of that redundancy. A new study, published Thursday in the journal Science, describes a microbe with the most streamlined genetic code yet.

Remarkably, the engineered bacteria can run on an abridged code, making it clear that a full genetic code isn’t required for life.

“Life still works,” said Wesley Robertson, a synthetic biologist at the Medical Research Council Laboratory of Molecular Biology in Cambridge, England, and an author of the new study.

Our DNA is built from four different molecular building blocks, called bases: adenine, thymine, guanine and cytosine. A sequence of hundreds or thousands of these bases — known in brief as A, T, C and G — forms a gene. Our cells translate the sequence of bases in genes to make proteins.

To make the translation work, our cells read the bases three at a time, in units called codons. Each codon matches one of the 20 different amino acids that are available in the cell. It’s these amino acids that a cell strings together to form proteins.

A key feature of the genetic code is that more than one codon can encode the same amino acid. For instance, the triplet of bases TCT leads to the amino acid serine. But so do five other codons — TCC, TCA, TCG, AGT and AGC. All told, 61 different codons give rise to the 20 amino acids. Another three codons tell our cells when they have reached the end of the gene. With 64 codons in total, the genetic code is immensely redundant.

Scientists have puzzled over the bloated code of life ever since it came to light in the 1960s. With few exceptions, every species on Earth relies on the same 64 codons. Because the code is universal, scientists have speculated, there must be something essential about having so many ways to build a protein.

About a decade ago, scientists began testing this idea by building new, compressed genetic codes. Advances in DNA synthesis allowed them to construct genomes from scratch, eliminating some of the redundant codons to see whether cells could survive with a smaller code.

“You can start exploring what life will tolerate,” said Akos Nyerges, a synthetic biologist at Harvard Medical School who has been working on shrinking the genetic code. “We can finally test these alternative genetic codes.”

Dr. Robertson and his colleagues at the Medical Research Council have been working toward the same goal. Both teams have been tinkering with Escherichia coli, a species of bacteria that dwells in the human gut and has been intensively studied for more than a century. They picked out redundant codons to eliminate, hoping they wouldn’t harm the microbe in the process. Dr. Robertson and his colleagues, for instance, set out to reduce the six serine codons to just two.

These plans demand tremendous amounts of engineering. The genome of Escherichia coli is about four million bases long, and each type of codon appears in thousands of different places along its length. To carry out so many changes, the researchers must build entire genomes from scratch.

(to be continued)

Translation

科學家正在學習改寫生命密碼（1/2）

在基因工程的偉大壯舉中，科學家們創造了一種與所有自然物種截然不同的蛋白質合成方式的細菌。

所有生命的核心都是密碼。我們的細胞利用它將DNA中的信息轉化為蛋白質。楓樹也是。鎚頭鯊也是。香菇也是。除了一些細微的差異外，遺傳密碼是通用的。

遺傳密碼也是冗拙的。 DNA可以用多種方式編碼出相同的蛋白質組成部分。長期以來，研究人員一直在爭論這種冗拙的目的 - 或者這是否只是歷史的偶然。

由於基因工程的進步，研究人員現在可以做的不僅僅是爭論。在過去的十年裡，科學家們建構了擁有更小密碼的微生物，這些密碼沒有其中一些冗拙。週四發表在《科學》雜誌上的一項新研究描述了一種擁有迄今為止最精簡遺傳密碼的微生物。

值得注意的是，這種工程細菌能夠以簡化的密碼運行，這清楚地表明生命並不需要完整的遺傳密碼。

英國劍橋大學醫學研究委員會分子生物學實驗室的合成生物學家、亦是這項新研究的作者 Wesley Robertson說: 「細菌生命依然在運作」。

我們的DNA由四種不同的分子結構單元組成，稱為鹼基：腺嘌呤、胸腺嘧啶、鳥嘌呤和胞嘧啶。數百或數千個鹼基（簡稱A、T、C和G）的序列構成一個基因。我們的細胞翻譯出基因中的鹼基序列來製造蛋白質。

為了進行翻譯，我們的細胞每次讀取三個鹼基，這些鹼基以密碼子(codons)為單位。每個密碼子與細胞中20種不同的胺基酸中的一種相符。正是這些胺基酸被細胞串聯起來形成蛋白質。

遺傳密碼的一個關鍵特徵是，同一種胺基酸可以由多個密碼子編碼出來。例如，鹼基三聯體 TCT 編碼的胺基酸是絲胺酸。其他五種密碼子 - TCC、TCA、TCG、AGT 和 AGC - 也編碼出絲胺酸。總共有 61 種不同的密碼子編碼出 20 種胺基酸。另外三種密碼子負責通知細胞何時到達基因的尾端。遺傳密碼總共有 64 個密碼子，冗拙度極高。

自 20 世紀 60 年代生命密碼被揭露以來，科學家們一直對其繁瑣的編碼方式感到困惑。除了少數例外，地球上的所有物種都依賴相同的 64 個密碼子。科學家推測，由於密碼具有通用性，因此存在如此多的蛋白質建構方式必然存在某種必需性。

大約十年前，科學家開始透過建立新的壓縮遺傳密碼來驗證這個想法。 DNA合成技術的進步使他們能夠從零開始建立基因組，消除一些冗餘的密碼子，以觀察細胞是否能夠在更短的密碼下生存。

一直致力於縮短遺傳密碼的長度的哈佛醫學院合成生物學家Akos Nyerges說道: 「你可以開始探索生命能夠承受什麼」; 「我們終於可以測試這些替代的遺傳密碼了」。

Robertson 博士和他在醫學研究委員會的同事們一直朝著同一個目標努力。兩個團隊都在對大腸桿菌進行研究，大腸桿菌是一種寄居在人體腸道中的細菌，一個多世紀以來一直受到人們的深入研究。他們挑選出需要消除大腸桿菌的冗餘密碼子，希望消除這些密碼子不會對這微生物造成傷害。例如，Robertson 博士和他的同事著手將六個絲胺酸密碼子減少到兩個。

這些計劃需要大量的工程改造。大腸桿菌的基因組長度約為400萬個鹼基，每種密碼子都出現在其全長的數千個不同位置。為了進行如此多的改變，研究人員必須從頭開始建構整個基因組。

（待續）