觀點(diǎn)：合成生命

Designing genomes from scratch will be the next revolution in biology.

By J. Craig Venter | October 1, 2011

作者：J.Craig Venter | 2011年10月1日

A little over one year ago, my team at the J. Craig Venter Institute announced the construction of the first cell completely controlled by a synthetic genome. After 8 years of work on DNA synthesis, assembly, and error correction, and on new ways to transplant and boot up chromosomes, we succeeded in creating a cell that used only a chemically synthesized chromosome to code for all aspects of the cellular phenotype.

一年多以前，我們?cè)贘.Craig Venter研究院 (J.Cragi Venter Institute, JCVI) 的研究小組宣布了首例人造細(xì)胞的誕生,。8年來,，我們致力于研究DNA的合成、組裝,、糾錯(cuò),，以及染色體的移植、增殖的新方法,。最后,，在僅靠化學(xué)合成的染色體的情況下，成功編譯了控制細(xì)胞表型的基因信息,，并且合成了細(xì)胞,。

DNA is the software of the cell, and our studies have shown that when we change the software we change the species. Because it is based on the digitized DNA sequence, the design of synthetic genomes provides a true interface between the computer and biological life. While genome design will dominate the future, the field has been limited to a few gene changes as a part of pathway design and to the engineering of novel biological circuits, such as oscillators, that can be used to construct semisynthetic biological machines.

DNA相當(dāng)于細(xì)胞的軟件,。我們的研究證明了當(dāng)軟件（也就是DNA）被改變的時(shí)候,，生物種類也會(huì)相應(yīng)改變。因?yàn)楹铣苫蛐蛄械脑O(shè)計(jì)是建立在DNA序列數(shù)字化的基礎(chǔ)上,，所以該設(shè)計(jì)也創(chuàng)建了電腦技術(shù)和生命科學(xué)的交互區(qū)域,。雖然基因設(shè)計(jì)將會(huì)主宰未來，但是目前仍有所局限：只能改變用于半合成生物機(jī)器的細(xì)胞通路設(shè)計(jì)和生物線路工程（例如生物震蕩器）（注1）上的少數(shù)基因序列,。

One major limitation is the cost—in both money and time—associated with genome modification. For example, it required over a decade of work and reportedly more than $100 million for the team at DuPont to make a dozen or so modifications to the E. coli genome so that it would convert glucose into propanediol to make “renewably sourced” fibers. And while some clever techniques for codon modification in E. coli have emerged recently from the laboratory of George Church, these are a long way from genomes designed and constructed to perform unique metabolic activities.

該技術(shù)的局限性在于基因改進(jìn)所需的時(shí)間和金額,。 例如，Dupont的研究小組耗時(shí)12年,，耗資10萬美金才成功地修改了大腸桿菌基因序列上12個(gè)左右的堿基對(duì),。修改后,，大腸桿菌可以把葡萄糖轉(zhuǎn)化為丙二醇，從而制造可再生的纖維,。雖然最近幾年從George教會(huì)實(shí)驗(yàn)室興起的,、成熟的密碼子修改技術(shù)在大腸桿菌上得到應(yīng)用，但是這離設(shè)計(jì)和構(gòu)建能夠執(zhí)行特定的新陳代謝活動(dòng)的基因組還有很長一段距離,。

The tools and techniques developed by my team to assemble a completely synthetic bacterial genome, while relatively efficient (we built the entire 1.1-million-base-pair synthetic genome in less than one month), are also still quite expensive ($0.30 per base pair) due to the current cost of oligonucleotide synthesis. Fortunately, this work has helped create a demand for rapid, accurate, cheap DNA synthesis, which has led to some very novel approaches that could help reduce these costs. Over the past 23 years, the cost of DNA sequencing has dropped 8 orders of magnitude. Similar improvements with DNA synthesis await technological breakthroughs that are tantalizingly close.

我們的研究小組改進(jìn)的技術(shù)可以合成并組裝出一套完整的病毒基因組,。雖然效率相對(duì)較高（可在一個(gè)月內(nèi)構(gòu)建了11萬對(duì)序列的基因組），但是受限于當(dāng)今的核酸合成技術(shù),，花費(fèi)不菲（2元人民幣每對(duì)核苷酸序列）,。幸運(yùn)的是，這項(xiàng)工作要求能夠快速,、準(zhǔn)確,、經(jīng)濟(jì)地合成DNA。這樣的需求刺激了技術(shù)革新,，導(dǎo)致DNA合成費(fèi)用的降低,。在過去的23年，DNA測(cè)序的費(fèi)用降低了8個(gè)數(shù)量級(jí),。我們期待著技術(shù)上巨大的革新,，那時(shí)DNA合成領(lǐng)域?qū)?huì)得到類似的進(jìn)步。

譯者注：

1. 細(xì)胞通路設(shè)計(jì)和生物線路工程屬于合成生物學(xué)的范疇,。該領(lǐng)域的一個(gè)應(yīng)用是設(shè)計(jì)出自然界中不存在的生物系統(tǒng),。例如，使用酵母細(xì)胞制造出合成電路,，細(xì)胞之間可通過細(xì)胞通路進(jìn)行連接,。這些酵母細(xì)胞經(jīng)過基因修改后，能夠基于設(shè)定的標(biāo)準(zhǔn)來感應(yīng)周遭環(huán)境,，并通過分泌出分子向其它酵母細(xì)胞發(fā)送信號(hào),。因此，這些不同的細(xì)胞能像樂高玩具的積木塊一樣連接在一起,，產(chǎn)生更復(fù)雜的電路,，完成更復(fù)雜的“電子功能”。