我們對于人類基因組的奧秘知道的越多,，對DNA的整體工作機制卻懂得的更少,。然而,，一切奧秘還是有跡可尋...
      
   編者案：“不要以為'垃圾基因’真的是垃圾”
   “心臟功能紊亂：概率99%,，潛伏并早期發(fā)病致死,。預期壽命：30.2年”
   一出生,，文森特的壽命和死亡原因就已經被知曉,。他的劣質基因意味著他所能期望的最佳工作就是去當一名清潔工，而不是去實現自己的雄心,，成為一名宇航員,。
    上面描述的正是科幻電影“千鈞一發(fā)”中的開始場景，在未來每個人的一生將由他們自己的基因決定,?！扒рx一發(fā)”于1997年公映，而當時人類基因組計劃正在執(zhí)行過程中,。電影情節(jié)反映了當時人們的普遍認識：人類不久就能夠通過基因預測個體的未來,。“存在一種信念，我們可以通過研究基因的自身和差異性,，來回答大量關于人類自身的問題”,，人類基因組計劃參與者，倫敦國王大學基因學家提姆.斯佩克特說,。
   時至今日,，美好的期望卻似乎更加遙遠。在人類基因組計劃進行過程中,，另外一個重要項目被啟動,，以試圖理解人類基因組中發(fā)現的基因比特到底在表達著些什么。本周公布的結果顯示,，我們的基因組已經比十年前生物學家所想象的更加復雜和神秘莫測,。
   回溯1960年，一幅美麗的圖片展現在人們面前,。我們的基因原來由蛋白質菜單組成,。雙螺旋結構可以通過解鏈來使RNA執(zhí)行菜單的復制，并將其傳送至細胞內部的蛋白質工廠,。然而直至70年代,，人們發(fā)現只有很少的一部分基因編碼用于蛋白質制造,，而現在我們知道這一比例不到1.2%。那么剩下的那一部分基因編碼在做什么,？有些人假設它們一定在執(zhí)行某些功能,，而另一些人則認為它們都是垃圾。“人類基因中至少90%的部分是無用的,，或者說是垃圾”,，基因學家Susumu Ohno在1972年寫道。
   Ohno當時就知道,，或者認為,，一些并沒用來執(zhí)行蛋白質編碼的DNA仍然在一些過程中扮演著重要的角色,。比如,，制造基因的RNA拷貝過程 - 轉錄- 一些蛋白質簇在基因附近被綁定至特定序列。這些被稱為轉錄因子的蛋白質,，通過控制基因來加速或阻斷轉錄過程,，而組裝成的特定序列被稱作調節(jié)DNA或開關。
   那么到底有多少DNA作為開關而工作,，或者說,，還執(zhí)行一些其它功能？為了提供一幅基因組的不同組件各自功能的全景圖,，ENCODE（ DNA元素百科全書）項目于2003年成立,。ENCODE項目由遍及全世界，并使用各種技術手段的不同小組構成,。針對僅僅1%基因的前期研究結果于2007年發(fā)布,。本周，所有基因的研究結果也已經發(fā)布,，并且在“Science”和其他期刊上公開發(fā)表大約30篇論文,。
   ENCODE項目試圖從眾多事務中尋找控制基因活動的開關。研究者通過獲取已知的轉錄因子并觀察它們將綁定的DNA序列來研究,。到目前為止,，研究者已經發(fā)現4百萬點位，約占全部基因序列的8.5%,，這一結果遠遠超過任何人的期望,。
   即便如此，這一結果也僅僅是對開關的最終真實數字的一個粗略估計,，因為ENCODE還沒有研究每一種細胞類型,，或每一種轉錄因子?！皳覀兊臉酚^估計,，開關大約占基因序列的18%到19%”,，英國劍橋大學歐洲生物信息研究所的尤恩.伯尼說，他目前正在主持ENCODE項目的數據分析工作,?！拔覀兛吹奖仍绕谕嗟枚嗟拈_關點位，并且看起來每一部分基因組都和開關相鄰,?！?/span>
    但是，新的發(fā)現和科學結論非常驚人,，但這些發(fā)現卻并沒有顯示這些開關到底在做些什么有益的工作,。比如，許多開關在過去或許執(zhí)行過一些角色,，但現在被斷開了,。
   另一個巨大的驚奇之處是調節(jié)基因在整個基因組中分布的相當廣泛，其中許多存在于過去被認為是“荒地”的基因之間很長的片段中間,。大約95%的基因組處于大約10000個基礎的開關對之間,。“這意味著幾乎所有的基因組都在做些什么,，或者說如果你更改它們的話,，就可能對某些地方的某些東西產生作用”，伯尼說,。這些開關工作的實際方式看起來比我們最初設想的要復雜的多,。一個ENCODE項目的研究發(fā)現單個開關可以影響多個基因。進一步說,，多數基因可以同時被大量的開關影響,。“幾乎我們觀察的每個基因都和DNA的其它片段存在物理接觸,，且從來不僅僅是1個,，而是5個，8個甚至10個,，并且每個上面都有RNA,，蛋白質和組蛋白”，一個來自伍斯特市馬薩諸塞大學醫(yī)學院的小組成員喬布斯.德克說,。
    這一結果有助于解釋一個生物學上最大的謎團：消失的遺傳特征,。我們都知道存在大量的遺傳基因會導致諸如身高或糖尿病的病態(tài)變異，但病態(tài)變異卻只在擁有這一遺傳基因的后代中非常小的一部分人中發(fā)生,。
    丟失的遺傳變異 
   存在這么一個假設：基因變異是彼此獨立發(fā)生的,，因此其結果是可加性的：如果你擁有某種會增加疾病風險的變異，比如說,，一個變異會增加心臟病發(fā)作風險5%而另一個變異增加10%,，那么你總的風險為15%,。但是德克的發(fā)現卻顯示，多個變異產生的綜合效應可能是可乘性的：某些變異自身作用不大,，但是和多個變異疊加后卻產生乘數效應,。
   “我確信很多遺傳變異的丟失，是因為多重基因,，多重非編碼變體和多重環(huán)境因素導致的,，”新漢普郡達特默斯蓋澤爾醫(yī)學院的詹森.莫爾說?！爸詴嬖诖罅窟z傳變異被丟失的現象,，是因為我們忽略在已知的生物學領域存在大量復雜的相互作用關系?！?/span>
   所以在超過20%的基因組中都存在調節(jié)開關,，無論它們工作或不工作。那么其它的基因組呢,？ENCODE試圖通過確定基因組中各自參與特定生化反應的映射關系來回答這個問題,，并顯示到底有多少基因組將參與日常運作,。研究結果顯示超過80%的基因組是活動的,，多數參與并被轉碼到RNA。
   既然這些RNA并不負責運送制造蛋白質的編碼,，那么它們負責做什么呢,？目前我們已經知道在已存具備大量不同功能的RNA中，多數都將參與調節(jié)基因活動,，比如微RNA,。進一步說，一些非編碼RNA看起來在執(zhí)行一些未知的工作,。
   “它們可能像出租車一樣負責在基因組附近傳送蛋白質,，但他們也能發(fā)揮橋梁的作用，將基因組的不同部分連接起來”,，加利福尼亞州拉賀亞市斯克里普斯研究中心的凱文.莫里斯說,。而其它的則像一個捕鳥器一樣，通過吸收編碼RNA來降低蛋白質生產,。
   到目前為止具備已知功能的RNA還不到全部基因組的80%,。一個解釋是大多數的RNA譯碼過程都是無用的，僅僅是過分活躍而又不知道如何終止DNA向RNA譯碼的過程中產生的白噪聲,。這就像在屋子里面養(yǎng)貓捕鼠卻無法制止貓捕殺鄰居家的小鳥一樣,。
  “非編碼DNA的轉錄過程并不會自動標記其功能”，加拿大安大略湖圭爾夫大學研究基因進化的瑞安.格雷戈里說,?！拔也徽J為ENCODE會顯示98%非編碼DNA中的多數具備調節(jié)功能,。使用如此多的非編碼DNA去調節(jié)區(qū)區(qū)20000個基因是令人驚訝的?！?/span>
   只有為數不多的幾個生物學家認為多數非編碼RNA在發(fā)揮重要的作用,，其中最直言不諱的是澳大利亞布里斯班昆士蘭大學的約翰.馬蒂克?！笆菚r候讓噪聲理論的鼓噪者們來解釋解釋,，為何有這么多基因組顯示其功能跡象？”
   但是做事并不代表做有用的事,，確實存在充足的理由來認為我們大多數的DNA并不在發(fā)揮重要的作用,。對于起步階段的人而言，設想我們都有幾十個新的基因變異,。華盛頓州西雅圖市系統(tǒng)生物研究所的約瑟夫.納多說,，我們中的多數都擁有一到五個對正常基因功能和蛋白質編碼存在負面影響的基因變異,。
   如果我們擁有的DNA中多數都是致命的,，人們將會比胚胎和幼兒由于不良基因變異導致的死亡更快的獲取有害的基因變異?！叭绻蚪M中存在有效功能的部分在增長,，問題是：我們如何才能夠忍受這一切？為什么我們不會在若干次變異后死亡,？”納多問,。
   一個獲取給定DNA片段重要性的方法是看是否這一片段可以累積存在而不存在不良后果，或者說可以在自然選擇淘汰不良變異后果的過程中幸免遇難,，并一個種群中持續(xù)不變,。“蛋白質編碼序列中70%的核苷酸變動將由于有害的后果而遭到淘汰,，但是90%的非編碼序列卻被保留下來,，”牛津大學的克里斯.龐廷說?！斑@一點告訴我們編碼序列的變異較非編碼序列的變異重要的多,。”
   伯尼說ENCODE項目已經發(fā)現針對靈長目的特定轉錄RNA,，并且其中有些看起來正處于人類競爭選擇的壓力之下,。
   另外一種評估DNA中給定基因編碼重要性的方法是刪除并觀察其后果。這一實現顯然不能針對人類進行,，然是在針對小白鼠的實驗中發(fā)現大量功能性非編碼DNA的刪除看起來并沒有造成明顯的后果,。而且，刪除諸如酵母菌的許多蛋白質編碼基因，看起來也不會造成明顯的后果,。
   一個解釋是在良好的實驗室環(huán)境下,，生物體即使不具備某些在實際競爭環(huán)境下至關重要的基因，也可以繼續(xù)生存,。另一個解釋是在生物基因中存在大量冗余備份,。盡管實驗者期望變異會消除冗余，仍然可能存在一些情形能夠是生物維持生存,。
  “冗余會讓系統(tǒng)更加強健,，”德克說?！叭绻魏谓o定的DNA片段都僅僅是上下文的一部分,，則刪除這些片段只會導致有限的后果。我認為這可以解釋為什么我們能夠容忍個體之間存在巨大的差異,，卻仍然能夠一起在街上漫步”,。
   第三個解釋是大多數我們的DNA都沒那么重要，雖然物種之間基因組存在大小的差異,，而物種復雜性和其基因組尺寸卻沒有太大的相關性,。并不存在明顯的理由表明石肺魚確實需要40倍于我們，400倍于河豚的DNA,。
    因為它們能 
   格雷戈里已經發(fā)現某些動物,，比如變態(tài)中的青蛙細胞需要快速分裂，并擁有比其它動物小的基因組,。這顯示生物體傾向于累積DNA直至產生有害的后果,，而不是像住大房子的人傾向于拿東西填滿閣樓而住小房子的人總是不斷把東西往外清。
   正因如此,，一些秘密將繼續(xù)保持下去。雖然一些證據表明我們的多數基因并沒有那么重要,，ENCODE項目的結果仍然顯示我們基因組中的多數區(qū)域還將做些事情,。一個答案是這些區(qū)域中的多數部分將不會導致重大后果?！八鼈兓蛟S會產生一些后果,。它們可以改變臉部解剖外形，”龐廷說,?！八鼈兛梢援a生較小，并且和進化無關的效應,?！?/span>
   盡管如此，伯尼仍然認為基因組的有些區(qū)域是至關重要的,?！拔覀冞€不能決然的回答到底這些區(qū)域有多重要,，但是我們已經發(fā)現更多的事實，并且較先前所有人所懷疑的更為重要,，”他說,。“人們經常說它們不過是蛋白質編碼區(qū)域而已,，多不了多少,。不是多不了多少，而是多得多,?！?/span>
   當ENCODE項目的工作開始時，伯尼自己就高度懷疑非編碼RNA在基因功能中的作用,。他甚至和馬蒂克賭一箱香檳酒,，只有不到20%的非編碼RNA是有用的?！翱雌饋砦液苡锌赡茌數暨@個賭局,，”他說。
   然而,，距離他們任何一方贏得賭局還有很長一段時間,。實際上，將數百萬基因區(qū)域中具備功能的部分標識出來是一個需要耗費數十年的艱巨任務,。根本上說,，證明特定基因區(qū)域重要性的唯一方法就是證明該區(qū)域的變異將對人造成影響，而這一過程非常困難,。盡管,，在某些情形下，證據已經存在：通過研究基因變異和疾病之間映射關系而標記出的重要基因變異常常和ENCODE項目結果相符,?！岸鄶禃r候我們我們獲取的結果要么和ENCODE研究結果完全相符，或非常接近,，”伯尼說,。
   這一結果已經給我們提供了關于疾病原因的線索。比如,，克羅恩病的一些基因變異就和ENCODE項目發(fā)現的被稱為T-helper的免疫細胞中的開關被激活有關,。
　　然而，看起來我們對于基因組了解的越多,，我們知道反而越少,。“我們的基因知道如何制造一個人，但是如果認為基因組的整張菜譜非常簡單并且已經完全展開則是不折不扣的妄自尊大，”伯尼說,。“人類是我們自身能夠了解到的最復雜的事物,，且確確實實非常復雜?！?/span>
   無疑,，正如“千鈞一發(fā)”的電影中所描述的那樣，我們距離完全了解和懂得基因組還有很長的一段路要走,。事實上,，我們從來就沒有過進展?！八_實過于復雜,，”摩爾說。
    這種復雜性的一部分來自于我們的基因組和環(huán)境間存在多種交互方式,。“我認為DNA會變得更具可預測性,，但是這項研究的另一面要求我們懂得由于環(huán)境影響和自由意志所產生的諸多復雜個性－－那些我們能夠改變的事物，”伯尼說,，“DNA不是命中注定的”,。
   某種程度上，即使“千鈞一發(fā)”的作者也會認可的是,，文森特置自身基因缺陷于不顧,，堅持抗拒宿命并最終完成離開地球的愿望。
      

    新科學家記者 林達.格迪斯 

              The ever deepening mystery of the human genome    

                         05 September 2012 by Linda Geddes

For similar stories, visit the Genetics Topic Guide

• The more we learn out about the secrets of the human genome, the less we seem to know about all that DNA actually does. But there are some clues       

(Image: Laguna Design/SPL/Getty)

Editorial:             "Don't junk the 'junk DNA' just yet"

       "HEART disorder: 99 per cent probability, early fatal potential. Life expectancy: 30.2 years."

        At birth, the time and cause of Vincent's death were already known. His inferior genes meant that the best job he could hope to get was as a cleaner, rather than realising his ambition of becoming an astronaut.

        Thus begins the film Gattaca, set in a future when a person's potential is thought to be determined by their genes. Gattaca was released in 1997 during the middle of the Human Genome Project, and its plot reflected what many believed at the time: we'd soon be able to predict all kinds of things about people based on their genes. "There was this belief that we could answer huge amounts of things just by studying genes and gene variants," says geneticist Tim Spector of Kings College London, who was involved in the project.

  Yet today, this prospect seems more distant than ever. After the genome was sequenced, another major project was launched to try to understand which bits of the genome do what. The results, released this week, reveal that our genome is far more complex and mysterious than biologists imagined just a decade ago.

Back in the 1960s, a beautifully simple picture emerged. Our DNA consisted of recipes for proteins. The double helix could be unzipped to allow RNA copies of these recipes to be made and sent to the protein-making factories in cells. But by the 1970s, it had become clear that only a tiny proportion of our DNA codes for proteins - just 1.2 per cent, we now know. What about all the rest? Some assumed it must do something, others suggested it was mostly junk. "At least 90 of our genomic DNA is 'junk' or 'garbage' of various sorts," the geneticist Susumu Ohno wrote in 1972.

   Ohno knew, though, that some of the DNA that didn't code for proteins still played a vital role. For instance, the process of making RNA copies of genes - transcription - involves clusters of proteins binding to specific sequences near the genes. These proteins - called transcription factors - control the activity of genes by either boosting or blocking transcription, so the sequences to which they bind are known as regulatory DNA or switches.

 So how much DNA acts a switch, or has some other function? To provide an overall picture of which parts of the genome do what, the Encyclopedia of DNA Elements (ENCODE) project was set up in 2003. It involves many teams around the world using a variety of techniques. The results of a pilot studylooking at just 1 per cent of the genome were released in 2007. This week, the results of its study of the entire genome were released, with the publication of more than 30 papers in Nature and other journals.

 Among other things, ENCODE looked for switches that control gene activity. The researchers did this by taking known transcription factors and seeing which bits of DNA these proteins bound to. So far, they have found 4 million sites, covering 8.5 per cent of the genome - far more than anyone expected.

     Even this is likely to be a gross underestimate of the true number, because ENCODE hasn't yet looked at every cell type, or every known transcription factor. "When we extrapolate up, it's more like 18 or 19 per cent," says Ewan Birney of the European Bioinformatics Institute in Cambridge, UK, who is coordinating the data analysis for ENCODE. "We see way more switches than we were expecting, and nearly every part of the genome is close to a switch."

    But - and it is a big but - these findings do not show whether these switches actually do anything useful. Many of them may have played a role in the past, for instance, but are now "disconnected".

        The other big surprise is that these regulatory regions are widely dispersed throughout the genome, with many lying in the middle of long stretches between genes that were thought to be barren wastelands. More than 95 per cent of the genome may lie within 10,000 base pairs of a switch. "It means that nearly all of the genome is in play for doing something, or if you change it maybe it would have an effect on something somewhere," Birney says.

       The way in which these switches work is also turning out to be vastly more complicated than thought. One ENCODE study found that individual switches interact with many genes. What's more, most genes are being influenced by numerous switches at the same time. "Almost every gene we look at is physically touching other pieces of DNA, and it's never just one, it tends to be five, eight, 10 sites, and each site in turn has RNAs on it, proteins on it, histones on it," says team member Job Dekker of the University of Massachusetts Medical School in Worcester.

   This might help to explain one of biology's biggest puzzles: the mystery of the "missing heritability". We know there's a big genetic component to traits and diseases such as height and diabetes, but the genetic variants found so far typically account for only a tiny percentage of this heritability.

              The missing inheritance

    The assumption has been that genetic variants work in isolation, so their effects are additive: if you've got one variant that increases the risk of, say, heart disease 5 per cent and another that increases it 10 per cent, your overall risk is 15 per cent. But Dekker's discovery suggests that the effects of some variants can multiply: these variants may have a small effect on their own, but a much bigger effect if a person has certain other variants too.

   "I firmly believe that much of the missing heritability is due to complex interactions between multiple genes, multiple non-coding variants and multiple environmental factors," saysJason Moore of the Geisel School of Medicine at Dartmouth in Hanover, New Hampshire. "The reason we've missed a lot of the heritability for complex diseases could be because we've ignored the complexity of the interactions that we know exist in biology."

 So up to 20 per cent of the genome may consist of regulatory switches, working or otherwise. What about the rest? ENCODE tried to address this by mapping what proportion of the genome is involved in some kind of biochemical event, which might suggest how much of it is in daily use. The results suggest that up to 80 per cent of the genome is active, with much of it being transcribed into RNAs.

        This RNA is not carrying the codes for making proteins, so what is it for? We know that there are lots of different kinds of functional RNAs, many of which are involved in regulating gene activity, such as microRNAs. What's more, some non-coding RNA is turning out to perform other unexpected jobs.

 "They can work like taxi drivers to deliver proteins around the genome, but they can also tether one part of the genome to another and act as a bridge," says Kevin Morris of the Scripps Research Institute in La Jolla, California. Yet others act as decoys, reducing protein output by soaking up coding RNAs.

        But so far all the RNAs with known functions do not begin to add up to 80 per cent of the genome. One explanation is that most RNA transcripts are useless, being mere "noise" generated by overzealous enzymes that don't know when to stop transcribing DNA into RNA. It's like getting a cat to kill mice in your house, and not being able to stop it killing birds in the neighbourhood too.

  "Transcription of non-coding DNA does not automatically indicate function," says Ryan Gregory of the University of Guelph in Ontario, Canada, who studies genome evolution. "I don't think ENCODE will show that the majority of the 98 per cent of non-coding DNA in the human genome is functional for regulation. It would be astonishing if it took so much to regulate a mere 20,000 genes."

     Only a handful of biologists, the most vocal being John Mattick of the University of Queensland in Brisbane, Australia, think most non-coding RNAs will turn out to have an important role. "It's now up to the proponents of the noise theory to explain why there's so much of the genome that's showing functional signatures," says Mattick.

    But doing something is not the same as doing something useful, and there are good reasons to think that most of our DNA does not play a vital role. For starters, at conception we all have dozens of new mutations. Most of us have one to five mutations that adversely affect gene function in our protein-coding DNA alone, says Joseph Nadeau of the Institute for Systems Biology in Seattle, Washington.

  If most of our DNA were vital, populations would acquire harmful mutations faster than they lose them through the death of embryos and children with lots of nasty mutations. "If the fraction of the genome that's functional increases, the question is: how do we tolerate that? Why aren't we dead many times over?" asks Nadeau.

One way to get a sense of the importance of a given bit of DNA is to look at whether it can accumulate mutations without consequence or whether it remains unchanged in a population because natural selection eliminates any individuals with mutations. "Something like seven out of ten nucleotide changes in [protein] coding sequences get kicked out because they're deleterious, but nine out of ten changes in non-coding sequence don't get kicked out," says Chris Ponting of the University of Oxford. "That's telling us something about the importance of coding changes versus non-coding changes."

Birney agrees, although he says ENCODE has looked at the transcribed RNA that's specific to primates and found that some of it seems to be under selective pressure in humans.

              Another way to assess the importance of a given bit of DNA is to delete it to see what happens. This obviously can't be done in people, but in mice huge chunks of non-coding DNA that appeared to be functional have been deleted without any obvious effect. Then again, it is possible to delete many protein-coding genes from organisms such as yeast without any obvious effect, too.

 One explanation is that in cossetted lab conditions, organisms can manage without DNA that is essential for survival in more challenging environments. Another is that there is a lot of redundancy in the genome. Although you would expect mutations to eliminate redundancy, there may be some circumstances in which it can be maintained.

       "[Redundancy] could be what makes the system robust," says Dekker. "If any given piece of DNA is only part of the context, deleting it may have very limited effects. I think it may explain why we can tolerate huge variation between individuals yet we're all still walking down the street."

       A third reason to think most of our DNA isn't vital is that although there isenormous variation in genome size between species, there is very little correlation between the complexity of animals and their genome size. There is no obvious reason why the marbled lungfish needs around 40 times as much DNA as we do, and nearly 400 times as much as the green pufferfish, for instance.

 Because they can   

Gregory has found that some kinds of animals, such as metamorphosing amphibians whose cells need to divide rapidly at times, have smaller genomes than other animals. This suggests that organisms tend to accumulate DNA until its size becomes detrimental, rather like the way people in a big house tend to fill the attic with junk whereas those in small houses have to keep throwing things out.     

              So we are left with something of a mystery. Although several lines of evidence suggest that most of our DNA is far from essential, ENCODE's results suggest that most regions of our genome do do something. One answer could be that most of these regions do not do anything of any great consequence. "They may still have effects. They may change someone's facial anatomy," says Ponting. "They may have very small effects which evolution isn't acting upon."

Birney thinks some of these regions do matter, though. "We don't yet have a definitive answer to how much of it is important, but we've discovered a lot more things that could be important than anybody had ever suspected," he says. "People often say it's the protein coding regions, plus a bit more. It's not a bit more, it's a lot more."

When ENCODE's work started, Birney himself was also highly sceptical about the role of non-protein-coding RNAs in genome function. He even bet Mattick a case of vintage champagne that less than 20 per cent of non-coding RNAs would turn out to be useful. "I am definitely closer to losing this bet," he says.

It could be a long time before one of them gets the champagne, though. Working out which of the millions of regions ENCODE has identified as functional are actually important is an immense task that could take many decades. Ultimately, the only way to prove that a particular region is vital is to show that variants in this region have some effect on people, which is far from easy. In some cases, though, the evidence already exists: the positions of significant genetic variants identified by studies looking for associations between genetic variants and diseases often coincide with ENCODE regions. "Most of the time we have something that's either bang on top of those regions identified by [these] studies, or really close by," says Birney.

              This is already giving us clues about the causes of diseases. For example, some variants associated with Crohn's disease are in switches that ENCODE found are active in immune cells called T-helper cells.

 It seems, though, that the more we learn about the genome, the less we know. "Our genome knows how to make a human, but I think it is hubris to think that that recipe book would be simple and well laid out," says Birney. "We are one of the most complicated things that we know about, and indeed it does look very complicated."

  We're certainly a long way from the complete understanding of the genome portrayed in Gattaca. In fact, we may never achieve it. "It may well be too complex," says Moore.

              Part of this complexity comes from the many ways in which our genome interacts with the environment. "I think DNA will become more predictive, but the flip side of this research is understanding how much of complex traits are due to environmental effects, or free will - things that we can change," says Birney. "DNA is not destiny."

        To some extent, even the writers of Gattaca agreed. (Spoiler alert.) Despite Vincent's genetic inadequacies, he refused to accept his genetic fate and ultimately achieved his goal of leaving Earth.

Linda Geddes is a reporter for New Scientist