DNA

英

deoxyribonucleic acid

同

デオキシリボ核酸

関

リボ核酸 RNA

　

WordNet

1. the 4th letter of the Roman alphabet (同)d

PrepTutorEJDIC

1. deoxyribonucleic acidディオキシリボ核酸
2. ribonucleic acid・リボ核酸
3. deuteriumの化学記号

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/10/04 11:38:23」(JST)

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DNAの立体構造

デオキシリボ核酸（デオキシリボかくさん、英: deoxyribonucleic acid、DNA）は、核酸の一種である。

高分子生体物質で、地球上のある程度の生物において、遺伝情報を担う物質となっている（大部分のウイルスはRNAが遺伝情報を担っている。遺伝子を参照）。

DNA の構成物質と二重螺旋構造

相補的塩基対：AとT、GとCが水素結合でつながる。

紙上に記されたDNA配列

DNA はデオキシリボース（五炭糖）とリン酸、塩基 から構成される核酸である。塩基はアデニン、グアニン、シトシン、チミンの四種類あり、それぞれ A, G, C, Tと略す。デオキシリボースの1'位に塩基が結合したものをデオキシヌクレオシド、このヌクレオシドのデオキシリボースの5'位にリン酸が結合したものをデオキシヌクレオチドと呼ぶ。

ヌクレオチドは核酸の最小単位であるが、DNAはデオキシヌクレオチドの高分子である。核酸が構成物質として用いる糖を構成糖と呼ぶが、構成糖にリボースを用いる核酸はリボ核酸 (RNA) という。ヌクレオチド分子は、リン酸を介したフォスフォジエステル結合で連結し、鎖状の分子構造をとる。DNAには方向性があるという。複製の際、DNAポリメラーゼは5'から開始し、3'の合成で終えるからだ。転写のときもこの方向性に従う（DNA複製参照）。

2本の逆向きのDNA鎖は、シャルガフの法則による相補的な塩基 (A/T, G/C) による水素結合を介して、全体として二重らせん構造をとる。塩基の相補性とは、A、T、G、Cの4種のうち、1種を決めればそれと水素結合で結ばれるもう1種も決まる性質である。2つのヌクレオチド鎖が互いの方向に逆となるよう水素結合で結ばれるために二重らせんとなる。この相補的二本鎖構造の意義は、片方を保存用（センス鎖）に残し、もう片方は、遺伝情報を必要な分だけmRNAに伝達する転写用（アンチセンス鎖）とに分けることである。また、二本鎖の片方をそのまま受け継がせるため、正確なDNAの複製を容易に行うことができるため、遺伝情報を伝えていく上で決定的に重要である。さらにまれに起こる損傷の修復にも役立つ（詳しくは二重らせん）。多くの場合、DNAは環状構造をとっている（詳しくは超らせん参照）。

長さは様々で、塩基の対により形成されているため、長さの単位は二本鎖の場合 bp（base pair:塩基対）またはkbp (1kbp=1000bp)、一本鎖の場合 b または nt（base、nucleotide: 塩基、ヌクレオチド）。

DNAの化学的性質

• 穏やかな方法で単離されたDNAは白色のフェルト状繊維で、そのナトリウム塩の水溶液は粘性が高く、流動複屈折を示す。これは熱、酸、アルカリに容易に変性し、粘度は低下し、乾燥すると粉末となり、もはや繊維状になり得ない。この変化から分子量は数百万から2万〜3万程度に下がってしまう。この化学組成はアルカリに対しては安定性が高いが、酸には弱く、容易にプリンを遊離する。この変化に伴い、デソキシペントースのアルデヒド基が遊離し、シッフ試薬を赤紫に変色させる。この呈色反応をフォイルゲン反応と呼び、これを利用して、DNAを含む核や分裂中の染色体を赤紫に着色して観察できる。
• DNAの吸光度は塩基によって紫外線260nmを吸収極大としている。この値は、塩基が接近しているほど小さい。塩基が極めて整然と、かつ接近している二本鎖DNAよりも、不規則に配列しているときの一本鎖DNAのほうが光を吸収する力は強い。例えば、A₂₆₀=1,00である二本鎖DNAと同濃度の一本鎖DNAについて、A₂₆₀=1、37である（詳しくはDNAの巻き戻し参照）。
• 変性したDNA溶液から、未変性状態のDNA状態と同じDNAを作ることができる（詳しくは再生_(DNA)参照）。
• 異なる分子種から得た一本鎖の試料を混ぜて再結合DNAを形成させる手法をハイブリッド形成という。

DNAとRNA

DNAとRNAはともにヌクレオチドの重合体である核酸であるが、両者の生体内の役割は明確に異なっている。DNAは主に核の中で情報の蓄積・保存、RNAはその情報の一時的な処理を担い、DNAと比べて、必要に応じて合成・分解される頻度は顕著である。DNAとRNAの化学構造の違いの意味することの第一は「RNAはDNAに比べて不安定」である。両者の安定の度合いの違いが、DNAは静的でRNAは動的な印象を与える。

化学構造の相違

DNAとRNAの化学構造の違いの第一は、構成糖が、RNAはリボースで、リボースから2'位の水酸基で酸素が一つ少ない2'-デオキシリボースであることだ。これにより、構成糖の立体配座が異なる。DNAではリボースがC2'-エンド形構造を取ることが多いが、RNAでは2'位のヒドロキシ基の存在により立体障害が生じ、リボースがC3'-エンド型構造を取る。このためDNAはB型らせん構造を取りやすく、RNAはA型らせん構造を取りやすくなるという違いが生じる。この結果RNAのらせん構造は主溝が深く狭くなり、副溝が浅く広くなる。らせん構造についての詳細は、記事二重らせんに詳しい。

1本鎖RNAでは2'位のヒドロキシ基が比較的柔軟な構造を取り反応性もあるため、DNAと比較すると不安定である。水酸基の酸素には孤立電子対が2つあるため負の電荷を帯びており、例えば、近接したリン酸のリンは周囲を電気陰性度の高い酸素原子に囲まれて水酸基の酸素原子から求核攻撃を受けやすく、攻撃によりホスホジエステル結合が切れ、リン酸とリボースの骨格が開裂する可能性があるなどDNAと比べて不安定である。この特性から、翻訳の役割を終えたmRNAを直ちに分解することが可能になる（バクテリアでは数分、動物細胞でも数時間後には分解される）。安定RNAでは1本鎖に水素結合を形成し、らせん構造となるなど、多様な二次構造、三次構造を取り、安定性を増している。

糖に結合している塩基にも違いがあり、DNAはA、C、G、Tであるが、RNAはTがUに替わっている。ただし、DNA上にもUが稀に生じることがあり、また、塩基にTではなくUを用いるDNAを持つ生物も存在する（U-DNA参照）。圧倒的大多数の生物でDNAの構成塩基にUではなくTが用いられるのは、同じピリミジン塩基であるCは自然の状態でも脱アミノ化することでUに置き換わることがあるからだ。そのため、U－DNAは頻繁に塩基配列が変化し、またそれを防ぐためには、損傷してUに変化したCと元々がUであるのと識別する必要があるという問題がある。TはUの2'にメチル基がついている構造をしている。メチル基は水素結合に係わるものの他の原子には殆ど反応しない。また、Uに比較してCからは容易に生じず、Cの損傷によって生じたUを容易に検出できる。 以上より、DNAではUではなくTが用いられているが、ウラシルはチミンよりエネルギー的に有利であるため、RNAではウラシルが用いられている。

物理化学的性質の相違

DNAとRNAの物理化学的性質について。DNAとRNAはともに紫外線である波長260nm付近に吸収極大を持ち、230nm付近に吸収極小を持つ。この吸光度はタンパク質の280nmよりもずっと大きいが、これはDNAとRNAの塩基はプリンまたはピリミジンに由来するためである。ただし、二重らせん構造のDNAの場合、溶液を加熱するとその吸光度は増す（濃色効果）。これは、DNAは規則正しい2重らせん構造ゆえ、全体の吸光度は個々の塩基の吸光度の総和より小さい（淡色効果）が、熱によって水素結合が切れ、2重らせん構造が解け（核酸の変性）、個々の塩基が自由になり、独自に光を吸収するためである。また、DNAとRNAはアルカリ溶液中で挙動が異なる。RNAは弱塩基でも容易に加水分解するが、DNAは安定して存在する。

細胞内でのDNA

真正細菌において核DNAは通常環状DNAとしてむき出しの状態で存在し、細胞質で核様体を形成する。また、プラスミド (plasmid) と呼ばれる核外の環状DNAが存在することがある。

真核生物においては細胞核内に線状DNAとして存在し、ヒストンと結合して染色体を形成している。ちなみに動物細胞は直径が1000分の5ミリメートル程しかないが、その中のDNAをつなげてまっすぐに伸ばすと2メートルにも達する（ヒトの場合）ため、普段は非常に高度に折りたたまれている。染色体はヒストンによってDNAを収納するための箱といえる（詳細はクロマチン）。DNA合成酵素は、DNA合成の際にプライマーと呼ばれる短鎖RNAを必要とし、プライマーは後に除去されてしまうため、線状DNAはDNA合成の度に短くなってしまうことになるが、これを防ぐために末端修復酵素（telomerase; テロメレース）が働いて短くなった分を補うようになっている。このテロメレースの働きが鈍ることによって老化が進むとも言われている。

古細菌は真正細菌と同じように環状DNAとして細胞質に存在するが、真核生物と同じようにヒストン様タンパクと結合してクロマチン様構造をとる。

またオルガネラでもミトコンドリアや葉緑体は独自のDNAを持つ。このことがオルガネラの由来に関する膜進化説に対する細胞内共生説の証拠であるとされている。形状は環状のものもあれば、そうでないものもある。

細菌や酵母などではDNAは環状のプラスミドとして存在する。

DNAの含有量

核内のDNA含有量は生理的条件に左右されない。すなわち一般的な体細胞は二倍体で、卵・精子等は半数体である。つまり卵・精子の核のDNA含有量は、その生物の体細胞のほぼ半分である。DNA含有量は個々の生物で特有であり、一つの種類で、二倍体ならばどの種類の細胞であろうと値は一定である。脊椎動物では両生類では特に高い。哺乳類では種類ごとの含有量の差が小さく、6~7×10^－12gぐらいであり、鳥類はその半分ぐらいである。 この現象は、複製のためにあり、体細胞分裂ごとにDNAは2倍に増加して、2個の娘細胞に等分される。

DNAの合成は染色体が出現する分裂期ではなく、静止核の時期である間期のS期に行われ、分裂期は合成されたDNAを娘細胞に等分する時期に当たる。詳細は細胞周期参照。またDNAは分裂間期から分裂期までの間、転写をせず、安定な状態で、娘細胞の中に入れられる。

DNAの合成

デノボ合成

食物から摂った糖やアミノ酸などを元に肝臓で合成する。デノボ合成を参照。

サルベージ合成

食品から摂取されて分解経路に入ったヌクレオチドを再利用する。サルベージ経路を参照。

DNAの材料

ヌクレオチド及びその結合体であるポリヌクレオチド、DNA、RNAは生物を原料とするほとんどの食品に微量含まれており、魚の白子や動物の睾丸などでは含有率が高い。DNAを摂取すると、体内でいったんヌクレオチドに分解された後、ヌクレオシド3リン酸となり、RNA、DNAを効率的に合成する材料となる。

工業的に効率的に分離するための原料としてサケの白子やホタテガイの生殖巣などが利用されている。

遺伝情報の担い手としてのDNA

DNAの複製

全ての生物で、細胞分裂の際の母細胞から娘細胞への遺伝情報の受け渡しは、DNAの複製によって行われる。DNA の複製はDNAポリメラーゼによって行われる（詳しくはDNA複製を参照のこと）。

DNAが親から子へ伝わるときにDNAに変異が起こり、新しい形質が付加されることがあり、これが種の保存にとって重要になることがある。

細菌など分裂によって増殖する生物は、条件が良ければ対数的に増殖する。その際、複製のミスによって薬剤耐性のような新たな形質を獲得し、それまで生息できなかった条件で生き残ることができるようになる。

有性生殖をする生物において、DNAは減数分裂時の染色体の組み換えや、配偶子の染色体の組み合わせにより、次世代の形質に多様性が生まれる。

生命の設計図としてのDNA

DNAは生命の設計図とよく言われるが、これはDNAの塩基配列がタンパク質のアミノ酸配列に対応しており、生命現象の大部分はタンパク質が担っているため、「タンパク質の設計図」=「生命の設計図」ということである。詳細は遺伝子参照。

連続する3つの塩基配列により、1個のアミノ酸がコードされる。生命体を構成する蛋白は20種のアミノ酸をからなっているので、開始・終止を示すコードを含めて4塩基で表現する為には、3つの塩基が必要かつ十分なものである（コドンを参照のこと）。

DNAのタンパク質合成によって新陳代謝やオペロンは行われる。

DNAによるタンパク質合成の順序はセントラルドグマに従う。DNAのタンパク質をコードする部分は外部からの刺激に応じ、RNAポリメラーゼにより、mRNAに転写される。その後、mRNA内でイントロンを除去して遺伝情報を編集（スプライシング）、次にリボソーム内でタンパク質に翻訳され（転写、翻訳を参照のこと）る。

3本鎖DNAの存在について

これまで2本鎖、もしくは1本鎖のみと考えられていたDNAであるが、近年3本鎖DNAの存在が示唆されてきている (reviewed in Right 2004; myong et al., 2006) 。

通常、DNAは真核生物の細胞内では2本鎖の状態で存在している。そのDNAのGC含量にもよるが、DNAは60℃前後で水素結合が壊れて1本鎖となる（Tm値）。逆に温度が下がり、0℃を下回るあたり（Bm値。若干の幅がある）で細胞質内のリン酸基を中心に3つの塩基が同じ高さに来ることがある。

この場合、事実上3本のDNA鎖が並列に存在することとなり、DNAは3本鎖となる。リン酸を必要とするため、単純なDNA溶液のみでの実験を行っても、in vitro（試験管内などの人工的に構成された条件下）での証明が難しい。今後はより再現性を高めた研究が進むものと期待されている。

3本鎖となったDNAにおいても、そのねじれは2本鎖の場合と変わらず、約10.5塩基ごとに1周である。3本鎖になることにより、2本鎖の場合のDNAの一次構造の保持への負担はより軽くなると思われがちである。しかし、実際に保持エネルギーを計測すると3本鎖DNAの方がエネルギーが大きく、遥かに不安定であることが実験的に証明されている (reviewed in Documentation 2006; leime et al., 2007) 。

なお、一部の担子菌類では、自然界で正常に存在している状態で3本鎖のDNAを有するものが見つかっている。これらのDNAが転写・複製される場合、3本が同時にほどけるのではなく、1本ずつ順番にほどけて複製される。そのため、これらの生物がDNA複製を行う際生体内のDNA量を計測すると、ある1点で急激に増加するのではなく段階的に増加していることがわかる。

DNAの利用

DNA鑑定

DNAの反復領域の違いをもとに、血液その他から人物の特定などを行う。犯罪捜査や親子鑑定に利用される。

医療

遺伝子治療やオーダメイド医療という、一人ひとりの個性に合った治療が可能になる。

工業

DNAの二重らせん構造を使って、微細な有機分子を捉えるフィルターが開発されている。

健康食品

DNA 小史

• 1869年: フリードリッヒ.ミーシャー（スイス）がDNAを発見、1871年にヌクレインという名で発表したが、彼はその役割を細胞内におけるリンの貯蔵と考えていた。（後にリヒャルト・アルトマン（ドイツ）によってヌクレインは核酸と改称される）
• 1885年: A.コッセルがアデニンを発見。86年にグアニン、93年にチミン、94年にシトシンも発見。
• 1909年: フィーバス・レヴィーンがリボースを構成糖とする核酸・RNAを発見。
• 1929年: 上述のフィーバス・レヴィーンがDNAの構成糖はデオシキリボースで、核酸にはDNAとRNAの2種類あることを発見。
• 1944年: オズワルド・アベリーらによって肺炎双球菌を用いて DNA が形質転換の原因物質であることが証明される。これはDNAが遺伝子本体であることを強く示唆したものであると理解された（当時、遺伝子の正体がDNAかタンパク質か論争が起こっていた）。
• 1952年: A.D.ハーシーとM.チェイスは、バクテリオファージを用いて、DNAが遺伝物質であることを直接に確認（ハーシーとチェイスの実験）。DNA が遺伝物質であることが決定的になる。
• 1953年: J.ワトソン、F.クリックがロザリンド・フランクリンやモーリス・ウィルキンスの研究データの提供によって DNA の二重らせん構造を明らかにした。
• 1956年: A.コーンバーグによってDNAポリメラーゼが発見される。コーンバーグはDNAポリメラーゼの精製にも成功している。
• 1957年: M.メセルソンとF.W.スタールによって DNA の半保存的複製が明らかにされる。
• 1967年: 岡崎令治らによって岡崎フラグメントが発見される。
• 1970年: H.スミスによって制限酵素 HindIIIが分離される。
• 1971年: ポール･バーグによって史上初の組み替えDNA実験を行った。発ガンウイルスの1種SV40のDNAを、ある種のバクテリアファージに組み替えることに成功。その後、実験室から漏れ出した大腸菌の危険性を指摘され、4年後アシロマ会議を主催する。
• 1975年: 上述のバーグの呼びかけでアシロマ会議開催。

詳しくは遺伝子を参照のこと

脚注

関連項目

• DNA複製
• 二重らせん
• 遺伝子
• 遺伝子工学
• プラスミド
• 核酸
• RNA
• PNA
• 染色体
• ゲノム
• セントラルドグマ
• アガロースゲル電気泳動
• PCR
• 相補的塩基対
• DNA鑑定
• DNAマイクロアレイ
• DNAシーケンサー
• DNAコンピュータ
• DNA - DNA分子交雑法
• DNAバーコーディング
• ミーム：文化における伝統を遺伝子に喩える通俗的な言い方として「何々のDNA」と用いられることがあるが、これに近い概念としてミームがある。学術的な場面以外で「何々のDNA」という言いまわしが用いられた場合、実質的には「何々のミーム」という意味で用いられていることが多い。

外部リンク

• （百科事典）「DNA」 - Medpediaにある「デオキシリボ核酸」についての項目。（英語）
• A Structure for Deoxyribose Nucleic Acid,NATURE No.4356 April 25,1953

wiki en

[Wiki en表示]

For a non-technical introduction to the topic, see Introduction to genetics.

For other uses, see DNA (disambiguation).

The structure of the DNA double helix. The atoms in the structure are colour coded by element and the detailed structure of two base pairs are shown in the bottom right.

The structure of part of a DNA double helix

Deoxyribonucleic acid (ⁱ/diˌɒksiˌraɪbɵ.njuːˌkleɪ.ɨk ˈæsɪd/; DNA) is a nucleic acid containing the genetic instructions used in the development and functioning of all known living organisms (with the exception of RNA viruses). The DNA segments carrying this genetic information are called genes. Likewise, other DNA sequences have structural purposes, or are involved in regulating the use of this genetic information. Along with RNA and proteins, DNA is one of the three major macromolecules that are essential for all known forms of life.

DNA consists of two long polymers of simple units called nucleotides, with backbones made of sugars and phosphate groups joined by ester bonds. These two strands run in opposite directions to each other and are therefore anti-parallel, one backbone being 3' (three prime) and the other 5' (five prime). This refers to the direction the 3rd and 5th carbon on the sugar molecule is facing. Attached to each sugar is one of four types of molecules called nucleobases (informally, bases). It is the sequence of these four nucleobases along the backbone that encodes information. This information is read using the genetic code, which specifies the sequence of the amino acids within proteins. The code is read by copying stretches of DNA into the related nucleic acid RNA in a process called transcription.

Within cells, DNA is organized into long structures called chromosomes. During cell division these chromosomes are duplicated in the process of DNA replication, providing each cell its own complete set of chromosomes. Eukaryotic organisms (animals, plants, fungi, and protists) store most of their DNA inside the cell nucleus and some of their DNA in organelles, such as mitochondria or chloroplasts. In contrast, prokaryotes (bacteria and archaea) store their DNA only in the cytoplasm. Within the chromosomes, chromatin proteins such as histones compact and organize DNA. These compact structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed.

Properties

Chemical structure of DNA. Hydrogen bonds shown as dotted lines.

DNA is a long polymer made from repeating units called nucleotides. As first discovered by James D. Watson and Francis Crick, the structure of DNA of all species comprises two helical chains each coiled round the same axis, and each with a pitch of 34 ångströms (3.4 nanometres) and a radius of 10 ångströms (1.0 nanometres). According to another study, when measured in a particular solution, the DNA chain measured 22 to 26 ångströms wide (2.2 to 2.6 nanometres), and one nucleotide unit measured 3.3 Å (0.33 nm) long. Although each individual repeating unit is very small, DNA polymers can be very large molecules containing millions of nucleotides. For instance, the largest human chromosome, chromosome number 1, is approximately 220 million base pairs long.

In living organisms DNA does not usually exist as a single molecule, but instead as a pair of molecules that are held tightly together. These two long strands entwine like vines, in the shape of a double helix. The nucleotide repeats contain both the segment of the backbone of the molecule, which holds the chain together, and a nucleobase, which interacts with the other DNA strand in the helix. A nucleobase linked to a sugar is called a nucleoside and a base linked to a sugar and one or more phosphate groups is called a nucleotide. Polymers comprising multiple linked nucleotides (as in DNA) are called a polynucleotide.

The backbone of the DNA strand is made from alternating phosphate and sugar residues. The sugar in DNA is 2-deoxyribose, which is a pentose (five-carbon) sugar. The sugars are joined together by phosphate groups that form phosphodiester bonds between the third and fifth carbon atoms of adjacent sugar rings. These asymmetric bonds mean a strand of DNA has a direction. In a double helix the direction of the nucleotides in one strand is opposite to their direction in the other strand: the strands are antiparallel. The asymmetric ends of DNA strands are called the 5′ (five prime) and 3′ (three prime) ends, with the 5' end having a terminal phosphate group and the 3' end a terminal hydroxyl group. One major difference between DNA and RNA is the sugar, with the 2-deoxyribose in DNA being replaced by the alternative pentose sugar ribose in RNA.

A section of DNA. The bases lie horizontally between the two spiraling strands. (animated version).

The DNA double helix is stabilized primarily by two forces: hydrogen bonds between nucleotides and base-stacking interactions among the aromatic nucleobases. In the aqueous environment of the cell, the conjugated π bonds of nucleotide bases align perpendicular to the axis of the DNA molecule, minimizing their interaction with the solvation shell and therefore, the Gibbs free energy. The four bases found in DNA are adenine (abbreviated A), cytosine (C), guanine (G) and thymine (T). These four bases are attached to the sugar/phosphate to form the complete nucleotide, as shown for adenosine monophosphate.

The nucleobases are classified into two types: the purines, A and G, being fused five- and six-membered heterocyclic compounds, and the pyrimidines, the six-membered rings C and T. A fifth pyrimidine nucleobase, uracil (U), usually takes the place of thymine in RNA and differs from thymine by lacking a methyl group on its ring. Uracil is not usually found in DNA, occurring only as a breakdown product of cytosine. However in a number of bacteriophages - Bacillus subtilis bacteriophages PBS1 and PBS2 and Yersinia bacteriophage piR1-37 - thymine has been replaced by uracil. In addition to RNA and DNA a large number of artificial nucleic acid analogues have also been created to study the proprieties of nucleic acids, or for use in biotechnology.

Major and minor grooves of DNA. Minor groove is a binding site for the dye Hoechst 33258.

Grooves

Twin helical strands form the DNA backbone. Another double helix may be found tracing the spaces, or grooves, between the strands. These voids are adjacent to the base pairs and may provide a binding site. As the strands are not directly opposite each other, the grooves are unequally sized. One groove, the major groove, is 22 Å wide and the other, the minor groove, is 12 Å wide. The narrowness of the minor groove means that the edges of the bases are more accessible in the major groove. As a result, proteins like transcription factors that can bind to specific sequences in double-stranded DNA usually make contacts to the sides of the bases exposed in the major groove. This situation varies in unusual conformations of DNA within the cell (see below), but the major and minor grooves are always named to reflect the differences in size that would be seen if the DNA is twisted back into the ordinary B form.

Base pairing

Further information: Base pair

In a DNA double helix, each type of nucleobase on one strand normally interacts with just one type of nucleobase on the other strand. This is called complementary base pairing. Here, purines form hydrogen bonds to pyrimidines, with A bonding only to T, and C bonding only to G. This arrangement of two nucleotides binding together across the double helix is called a base pair. As hydrogen bonds are not covalent, they can be broken and rejoined relatively easily. The two strands of DNA in a double helix can therefore be pulled apart like a zipper, either by a mechanical force or high temperature. As a result of this complementarity, all the information in the double-stranded sequence of a DNA helix is duplicated on each strand, which is vital in DNA replication. Indeed, this reversible and specific interaction between complementary base pairs is critical for all the functions of DNA in living organisms.

Top, a GC base pair with three hydrogen bonds. Bottom, an AT base pair with two hydrogen bonds. Non-covalent hydrogen bonds between the pairs are shown as dashed lines.

The two types of base pairs form different numbers of hydrogen bonds, AT forming two hydrogen bonds, and GC forming three hydrogen bonds (see figures, right). DNA with high GC-content is more stable than DNA with low GC-content.

As noted above, most DNA molecules are actually two polymer strands, bound together in a helical fashion by noncovalent bonds; this double stranded structure (dsDNA) is maintained largely by the intrastrand base stacking interactions, which are strongest for G,C stacks. The two strands can come apart – a process known as melting – to form two ssDNA molecules. Melting occurs when conditions favor ssDNA; such conditions are high temperature, low salt and high pH (low pH also melts DNA, but since DNA is unstable due to acid depurination, low pH is rarely used).

The stability of the dsDNA form depends not only on the GC-content (% G,C basepairs) but also on sequence (since stacking is sequence specific) and also length (longer molecules are more stable). The stability can be measured in various ways; a common way is the "melting temperature", which is the temperature at which 50% of the ds molecules are converted to ss molecules; melting temperature is dependent on ionic strength and the concentration of DNA. As a result, it is both the percentage of GC base pairs and the overall length of a DNA double helix that determine the strength of the association between the two strands of DNA. Long DNA helices with a high GC-content have stronger-interacting strands, while short helices with high AT content have weaker-interacting strands. In biology, parts of the DNA double helix that need to separate easily, such as the TATAAT Pribnow box in some promoters, tend to have a high AT content, making the strands easier to pull apart.

In the laboratory, the strength of this interaction can be measured by finding the temperature required to break the hydrogen bonds, their melting temperature (also called T_m value). When all the base pairs in a DNA double helix melt, the strands separate and exist in solution as two entirely independent molecules. These single-stranded DNA molecules (ssDNA) have no single common shape, but some conformations are more stable than others.

Sense and antisense

Further information: Sense (molecular biology)

A DNA sequence is called "sense" if its sequence is the same as that of a messenger RNA copy that is translated into protein. The sequence on the opposite strand is called the "antisense" sequence. Both sense and antisense sequences can exist on different parts of the same strand of DNA (i.e. both strands contain both sense and antisense sequences). In both prokaryotes and eukaryotes, antisense RNA sequences are produced, but the functions of these RNAs are not entirely clear. One proposal is that antisense RNAs are involved in regulating gene expression through RNA-RNA base pairing.

A few DNA sequences in prokaryotes and eukaryotes, and more in plasmids and viruses, blur the distinction between sense and antisense strands by having overlapping genes. In these cases, some DNA sequences do double duty, encoding one protein when read along one strand, and a second protein when read in the opposite direction along the other strand. In bacteria, this overlap may be involved in the regulation of gene transcription, while in viruses, overlapping genes increase the amount of information that can be encoded within the small viral genome.

Supercoiling

Further information: DNA supercoil

DNA can be twisted like a rope in a process called DNA supercoiling. With DNA in its "relaxed" state, a strand usually circles the axis of the double helix once every 10.4 base pairs, but if the DNA is twisted the strands become more tightly or more loosely wound. If the DNA is twisted in the direction of the helix, this is positive supercoiling, and the bases are held more tightly together. If they are twisted in the opposite direction, this is negative supercoiling, and the bases come apart more easily. In nature, most DNA has slight negative supercoiling that is introduced by enzymes called topoisomerases. These enzymes are also needed to relieve the twisting stresses introduced into DNA strands during processes such as transcription and DNA replication.

From left to right, the structures of A, B and Z DNA

Alternate DNA structures

Further information: Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid, Molecular models of DNA, and DNA structure

DNA exists in many possible conformations that include A-DNA, B-DNA, and Z-DNA forms, although, only B-DNA and Z-DNA have been directly observed in functional organisms. The conformation that DNA adopts depends on the hydration level, DNA sequence, the amount and direction of supercoiling, chemical modifications of the bases, the type and concentration of metal ions, as well as the presence of polyamines in solution.

The first published reports of A-DNA X-ray diffraction patterns— and also B-DNA used analyses based on Patterson transforms that provided only a limited amount of structural information for oriented fibers of DNA. An alternate analysis was then proposed by Wilkins et al., in 1953, for the in vivo B-DNA X-ray diffraction/scattering patterns of highly hydrated DNA fibers in terms of squares of Bessel functions. In the same journal, James D. Watson and Francis Crick presented their molecular modeling analysis of the DNA X-ray diffraction patterns to suggest that the structure was a double-helix.

Although the `B-DNA form' is most common under the conditions found in cells, it is not a well-defined conformation but a family of related DNA conformations that occur at the high hydration levels present in living cells. Their corresponding X-ray diffraction and scattering patterns are characteristic of molecular paracrystals with a significant degree of disorder.

Compared to B-DNA, the A-DNA form is a wider right-handed spiral, with a shallow, wide minor groove and a narrower, deeper major groove. The A form occurs under non-physiological conditions in partially dehydrated samples of DNA, while in the cell it may be produced in hybrid pairings of DNA and RNA strands, as well as in enzyme-DNA complexes. Segments of DNA where the bases have been chemically modified by methylation may undergo a larger change in conformation and adopt the Z form. Here, the strands turn about the helical axis in a left-handed spiral, the opposite of the more common B form. These unusual structures can be recognized by specific Z-DNA binding proteins and may be involved in the regulation of transcription.

Alternate DNA chemistry

For a number of years exobiologists have proposed the existence of a shadow biosphere, a postulated microbial biosphere of Earth that uses radically different biochemical and molecular processes than currently known life. One of the proposals was the existence of lifeforms that use arsenic instead of phosphorus in DNA.

A December 2010 NASA press conference stated that the bacterium GFAJ-1, which has evolved in an arsenic-rich environment, is the first terrestrial lifeform found which may have this ability. The bacterium was found in Mono Lake, east of Yosemite National Park. GFAJ-1 is a rod-shaped extremophile bacterium in the family Halomonadaceae that, when starved of phosphorus, may be capable of incorporating the usually poisonous element arsenic in its DNA. This discovery may lend weight to the long-standing idea that extraterrestrial life could have a different chemical makeup from life on Earth. The research was carried out by a team led by Felisa Wolfe-Simon, a geomicrobiologist and geobiochemist, a Postdoctoral Fellow of the NASA Astrobiology Institute with Arizona State University. This finding has, however, faced strong criticism from the scientific community; scientists have argued that there is no evidence that arsenic is actually incorporated into biomolecules. Independent confirmation of this finding has also not yet been possible.

Quadruplex structures

Further information: G-quadruplex

At the ends of the linear chromosomes are specialized regions of DNA called telomeres. The main function of these regions is to allow the cell to replicate chromosome ends using the enzyme telomerase, as the enzymes that normally replicate DNA cannot copy the extreme 3′ ends of chromosomes. These specialized chromosome caps also help protect the DNA ends, and stop the DNA repair systems in the cell from treating them as damage to be corrected. In human cells, telomeres are usually lengths of single-stranded DNA containing several thousand repeats of a simple TTAGGG sequence.

DNA quadruplex formed by telomere repeats. The looped conformation of the DNA backbone is very different from the typical DNA helix.

These guanine-rich sequences may stabilize chromosome ends by forming structures of stacked sets of four-base units, rather than the usual base pairs found in other DNA molecules. Here, four guanine bases form a flat plate and these flat four-base units then stack on top of each other, to form a stable G-quadruplex structure. These structures are stabilized by hydrogen bonding between the edges of the bases and chelation of a metal ion in the centre of each four-base unit. Other structures can also be formed, with the central set of four bases coming from either a single strand folded around the bases, or several different parallel strands, each contributing one base to the central structure.

In addition to these stacked structures, telomeres also form large loop structures called telomere loops, or T-loops. Here, the single-stranded DNA curls around in a long circle stabilized by telomere-binding proteins. At the very end of the T-loop, the single-stranded telomere DNA is held onto a region of double-stranded DNA by the telomere strand disrupting the double-helical DNA and base pairing to one of the two strands. This triple-stranded structure is called a displacement loop or D-loop.

Single branch	Multiple branches

Branched DNA can form networks containing multiple branches.

Branched DNA

Further information: Branched DNA and DNA nanotechnology

In DNA fraying occurs when non-complementary regions exist at the end of an otherwise complementary double-strand of DNA. However, branched DNA can occur if a third strand of DNA is introduced and contains adjoining regions able to hybridize with the frayed regions of the pre-existing double-strand. Although the simplest example of branched DNA involves only three strands of DNA, complexes involving additional strands and multiple branches are also possible. Branched DNA can be used in nanotechnology to construct geometric shapes, see the section on uses in technology below.

Vibration

DNA may carry out low-frequency collective motion as observed by the Raman spectroscopy and analyzed with a quasi-continuum model.

Chemical modifications

cytosine	5-methylcytosine	thymine

Structure of cytosine with and without the 5-methyl group. Deamination converts 5-methylcytosine into thymine.

Base modifications

Further information: DNA methylation

The expression of genes is influenced by how the DNA is packaged in chromosomes, in a structure called chromatin. Base modifications can be involved in packaging, with regions that have low or no gene expression usually containing high levels of methylation of cytosine bases. For example, cytosine methylation, produces 5-methylcytosine, which is important for X-chromosome inactivation. The average level of methylation varies between organisms – the worm Caenorhabditis elegans lacks cytosine methylation, while vertebrates have higher levels, with up to 1% of their DNA containing 5-methylcytosine. Despite the importance of 5-methylcytosine, it can deaminate to leave a thymine base, so methylated cytosines are particularly prone to mutations. Other base modifications include adenine methylation in bacteria, the presence of 5-hydroxymethylcytosine in the brain, and the glycosylation of uracil to produce the "J-base" in kinetoplastids.

Damage

Further information: Mutation

A covalent adduct between a metabolically activated form of benzo[a]pyrene, the major mutagen in tobacco smoke, and DNA

DNA can be damaged by many sorts of mutagens, which change the DNA sequence. Mutagens include oxidizing agents, alkylating agents and also high-energy electromagnetic radiation such as ultraviolet light and X-rays. The type of DNA damage produced depends on the type of mutagen. For example, UV light can damage DNA by producing thymine dimers, which are cross-links between pyrimidine bases. On the other hand, oxidants such as free radicals or hydrogen peroxide produce multiple forms of damage, including base modifications, particularly of guanosine, and double-strand breaks. A typical human cell contains about 150,000 bases that have suffered oxidative damage. Of these oxidative lesions, the most dangerous are double-strand breaks, as these are difficult to repair and can produce point mutations, insertions and deletions from the DNA sequence, as well as chromosomal translocations. These mutations can cause cancer. Because of inherent limitations in the DNA repair mechanisms, if humans lived long enough, they would all eventually develop cancer.

Many mutagens fit into the space between two adjacent base pairs, this is called intercalation. Most intercalators are aromatic and planar molecules; examples include ethidium bromide, acridines, daunomycin, and doxorubicin. In order for an intercalator to fit between base pairs, the bases must separate, distorting the DNA strands by unwinding of the double helix. This inhibits both transcription and DNA replication, causing toxicity and mutations. As a result, DNA intercalators may be carcinogens, and in the case of thalidomide, a teratogen. Others such as benzo[a]pyrene diol epoxide and aflatoxin form DNA adducts which induce errors in replication. Nevertheless, due to their ability to inhibit DNA transcription and replication, other similar toxins are also used in chemotherapy to inhibit rapidly growing cancer cells.

Biological functions

DNA usually occurs as linear chromosomes in eukaryotes, and circular chromosomes in prokaryotes. The set of chromosomes in a cell makes up its genome; the human genome has approximately 3 billion base pairs of DNA arranged into 46 chromosomes. The information carried by DNA is held in the sequence of pieces of DNA called genes. Transmission of genetic information in genes is achieved via complementary base pairing. For example, in transcription, when a cell uses the information in a gene, the DNA sequence is copied into a complementary RNA sequence through the attraction between the DNA and the correct RNA nucleotides. Usually, this RNA copy is then used to make a matching protein sequence in a process called translation, which depends on the same interaction between RNA nucleotides. In alternative fashion, a cell may simply copy its genetic information in a process called DNA replication. The details of these functions are covered in other articles; here we focus on the interactions between DNA and other molecules that mediate the function of the genome.

Genes and genomes

Further information: Cell nucleus, Chromatin, Chromosome, Gene, Noncoding DNA

Genomic DNA is tightly and orderly packed in the process called DNA condensation to fit the small available volumes of the cell. In eukaryotes, DNA is located in the cell nucleus, as well as small amounts in mitochondria and chloroplasts. In prokaryotes, the DNA is held within an irregularly shaped body in the cytoplasm called the nucleoid. The genetic information in a genome is held within genes, and the complete set of this information in an organism is called its genotype. A gene is a unit of heredity and is a region of DNA that influences a particular characteristic in an organism. Genes contain an open reading frame that can be transcribed, as well as regulatory sequences such as promoters and enhancers, which control the transcription of the open reading frame.

In many species, only a small fraction of the total sequence of the genome encodes protein. For example, only about 1.5% of the human genome consists of protein-coding exons, with over 50% of human DNA consisting of non-coding repetitive sequences. The reasons for the presence of so much noncoding DNA in eukaryotic genomes and the extraordinary differences in genome size, or C-value, among species represent a long-standing puzzle known as the "C-value enigma". However, some DNA sequences that do not code protein may still encode functional non-coding RNA molecules, which are involved in the regulation of gene expression.

T7 RNA polymerase (blue) producing a mRNA (green) from a DNA template (orange).

Some noncoding DNA sequences play structural roles in chromosomes. Telomeres and centromeres typically contain few genes, but are important for the function and stability of chromosomes. An abundant form of noncoding DNA in humans are pseudogenes, which are copies of genes that have been disabled by mutation. These sequences are usually just molecular fossils, although they can occasionally serve as raw genetic material for the creation of new genes through the process of gene duplication and divergence.

Transcription and translation

Further information: Genetic code, Transcription (genetics), Protein biosynthesis

A gene is a sequence of DNA that contains genetic information and can influence the phenotype of an organism. Within a gene, the sequence of bases along a DNA strand defines a messenger RNA sequence, which then defines one or more protein sequences. The relationship between the nucleotide sequences of genes and the amino-acid sequences of proteins is determined by the rules of translation, known collectively as the genetic code. The genetic code consists of three-letter 'words' called codons formed from a sequence of three nucleotides (e.g. ACT, CAG, TTT).

In transcription, the codons of a gene are copied into messenger RNA by RNA polymerase. This RNA copy is then decoded by a ribosome that reads the RNA sequence by base-pairing the messenger RNA to transfer RNA, which carries amino acids. Since there are 4 bases in 3-letter combinations, there are 64 possible codons ( combinations). These encode the twenty standard amino acids, giving most amino acids more than one possible codon. There are also three 'stop' or 'nonsense' codons signifying the end of the coding region; these are the TAA, TGA and TAG codons.

DNA replication. The double helix is unwound by a helicase and topoisomerase. Next, one DNA polymerase produces the leading strand copy. Another DNA polymerase binds to the lagging strand. This enzyme makes discontinuous segments (called Okazaki fragments) before DNA ligase joins them together.

Replication

Further information: DNA replication

Cell division is essential for an organism to grow, but, when a cell divides, it must replicate the DNA in its genome so that the two daughter cells have the same genetic information as their parent. The double-stranded structure of DNA provides a simple mechanism for DNA replication. Here, the two strands are separated and then each strand's complementary DNA sequence is recreated by an enzyme called DNA polymerase. This enzyme makes the complementary strand by finding the correct base through complementary base pairing, and bonding it onto the original strand. As DNA polymerases can only extend a DNA strand in a 5′ to 3′ direction, different mechanisms are used to copy the antiparallel strands of the double helix. In this way, the base on the old strand dictates which base appears on the new strand, and the cell ends up with a perfect copy of its DNA.

Interactions with proteins

All the functions of DNA depend on interactions with proteins. These protein interactions can be non-specific, or the protein can bind specifically to a single DNA sequence. Enzymes can also bind to DNA and of these, the polymerases that copy the DNA base sequence in transcription and DNA replication are particularly important.

DNA-binding proteins

Further information: DNA-binding protein

Interaction of DNA (shown in orange) with histones (shown in blue). These proteins' basic amino acids bind to the acidic phosphate groups on DNA.

Structural proteins that bind DNA are well-understood examples of non-specific DNA-protein interactions. Within chromosomes, DNA is held in complexes with structural proteins. These proteins organize the DNA into a compact structure called chromatin. In eukaryotes this structure involves DNA binding to a complex of small basic proteins called histones, while in prokaryotes multiple types of proteins are involved. The histones form a disk-shaped complex called a nucleosome, which contains two complete turns of double-stranded DNA wrapped around its surface. These non-specific interactions are formed through basic residues in the histones making ionic bonds to the acidic sugar-phosphate backbone of the DNA, and are therefore largely independent of the base sequence. Chemical modifications of these basic amino acid residues include methylation, phosphorylation and acetylation. These chemical changes alter the strength of the interaction between the DNA and the histones, making the DNA more or less accessible to transcription factors and changing the rate of transcription. Other non-specific DNA-binding proteins in chromatin include the high-mobility group proteins, which bind to bent or distorted DNA. These proteins are important in bending arrays of nucleosomes and arranging them into the larger structures that make up chromosomes.

A distinct group of DNA-binding proteins are the DNA-binding proteins that specifically bind single-stranded DNA. In humans, replication protein A is the best-understood member of this family and is used in processes where the double helix is separated, including DNA replication, recombination and DNA repair. These binding proteins seem to stabilize single-stranded DNA and protect it from forming stem-loops or being degraded by nucleases.

The lambda repressor helix-turn-helix transcription factor bound to its DNA target

In contrast, other proteins have evolved to bind to particular DNA sequences. The most intensively studied of these are the various transcription factors, which are proteins that regulate transcription. Each transcription factor binds to one particular set of DNA sequences and activates or inhibits the transcription of genes that have these sequences close to their promoters. The transcription factors do this in two ways. Firstly, they can bind the RNA polymerase responsible for transcription, either directly or through other mediator proteins; this locates the polymerase at the promoter and allows it to begin transcription. Alternatively, transcription factors can bind enzymes that modify the histones at the promoter; this will change the accessibility of the DNA template to the polymerase.

As these DNA targets can occur throughout an organism's genome, changes in the activity of one type of transcription factor can affect thousands of genes. Consequently, these proteins are often the targets of the signal transduction processes that control responses to environmental changes or cellular differentiation and development. The specificity of these transcription factors' interactions with DNA come from the proteins making multiple contacts to the edges of the DNA bases, allowing them to "read" the DNA sequence. Most of these base-interactions are made in the major groove, where the bases are most accessible.

The restriction enzyme EcoRV (green) in a complex with its substrate DNA

DNA-modifying enzymes

Nucleases and ligases

Nucleases are enzymes that cut DNA strands by catalyzing the hydrolysis of the phosphodiester bonds. Nucleases that hydrolyse nucleotides from the ends of DNA strands are called exonucleases, while endonucleases cut within strands. The most frequently used nucleases in molecular biology are the restriction endonucleases, which cut DNA at specific sequences. For instance, the EcoRV enzyme shown to the left recognizes the 6-base sequence 5′-GATATC-3′ and makes a cut at the vertical line. In nature, these enzymes protect bacteria against phage infection by digesting the phage DNA when it enters the bacterial cell, acting as part of the restriction modification system. In technology, these sequence-specific nucleases are used in molecular cloning and DNA fingerprinting.

Enzymes called DNA ligases can rejoin cut or broken DNA strands. Ligases are particularly important in lagging strand DNA replication, as they join together the short segments of DNA produced at the replication fork into a complete copy of the DNA template. They are also used in DNA repair and genetic recombination.

Topoisomerases and helicases

Topoisomerases are enzymes with both nuclease and ligase activity. These proteins change the amount of supercoiling in DNA. Some of these enzymes work by cutting the DNA helix and allowing one section to rotate, thereby reducing its level of supercoiling; the enzyme then seals the DNA break. Other types of these enzymes are capable of cutting one DNA helix and then passing a second strand of DNA through this break, before rejoining the helix. Topoisomerases are required for many processes involving DNA, such as DNA replication and transcription.

Helicases are proteins that are a type of molecular motor. They use the chemical energy in nucleoside triphosphates, predominantly ATP, to break hydrogen bonds between bases and unwind the DNA double helix into single strands. These enzymes are essential for most processes where enzymes need to access the DNA bases.

Polymerases

Polymerases are enzymes that synthesize polynucleotide chains from nucleoside triphosphates. The sequence of their products are copies of existing polynucleotide chains – which are called templates. These enzymes function by adding nucleotides onto the 3′ hydroxyl group of the previous nucleotide in a DNA strand. As a consequence, all polymerases work in a 5′ to 3′ direction. In the active site of these enzymes, the incoming nucleoside triphosphate base-pairs to the template: this allows polymerases to accurately synthesize the complementary strand of their template. Polymerases are classified according to the type of template that they use.

In DNA replication, a DNA-dependent DNA polymerase makes a copy of a DNA sequence. Accuracy is vital in this process, so many of these polymerases have a proofreading activity. Here, the polymerase recognizes the occasional mistakes in the synthesis reaction by the lack of base pairing between the mismatched nucleotides. If a mismatch is detected, a 3′ to 5′ exonuclease activity is activated and the incorrect base removed. In most organisms, DNA polymerases function in a large complex called the replisome that contains multiple accessory subunits, such as the DNA clamp or helicases.

RNA-dependent DNA polymerases are a specialized class of polymerases that copy the sequence of an RNA strand into DNA. They include reverse transcriptase, which is a viral enzyme involved in the infection of cells by retroviruses, and telomerase, which is required for the replication of telomeres. Telomerase is an unusual polymerase because it contains its own RNA template as part of its structure.

Transcription is carried out by a DNA-dependent RNA polymerase that copies the sequence of a DNA strand into RNA. To begin transcribing a gene, the RNA polymerase binds to a sequence of DNA called a promoter and separates the DNA strands. It then copies the gene sequence into a messenger RNA transcript until it reaches a region of DNA called the terminator, where it halts and detaches from the DNA. As with human DNA-dependent DNA polymerases, RNA polymerase II, the enzyme that transcribes most of the genes in the human genome, operates as part of a large protein complex with multiple regulatory and accessory subunits.

Genetic recombination

Structure of the Holliday junction intermediate in genetic recombination. The four separate DNA strands are coloured red, blue, green and yellow.

Further information: Genetic recombination

Recombination involves the breakage and rejoining of two chromosomes (M and F) to produce two re-arranged chromosomes (C1 and C2).

A DNA helix usually does not interact with other segments of DNA, and in human cells the different chromosomes even occupy separate areas in the nucleus called "chromosome territories". This physical separation of different chromosomes is important for the ability of DNA to function as a stable repository for information, as one of the few times chromosomes interact is during chromosomal crossover when they recombine. Chromosomal crossover is when two DNA helices break, swap a section and then rejoin.

Recombination allows chromosomes to exchange genetic information and produces new combinations of genes, which increases the efficiency of natural selection and can be important in the rapid evolution of new proteins. Genetic recombination can also be involved in DNA repair, particularly in the cell's response to double-strand breaks.

The most common form of chromosomal crossover is homologous recombination, where the two chromosomes involved share very similar sequences. Non-homologous recombination can be damaging to cells, as it can produce chromosomal translocations and genetic abnormalities. The recombination reaction is catalyzed by enzymes known as recombinases, such as RAD51. The first step in recombination is a double-stranded break caused by either an endonuclease or damage to the DNA. A series of steps catalyzed in part by the recombinase then leads to joining of the two helices by at least one Holliday junction, in which a segment of a single strand in each helix is annealed to the complementary strand in the other helix. The Holliday junction is a tetrahedral junction structure that can be moved along the pair of chromosomes, swapping one strand for another. The recombination reaction is then halted by cleavage of the junction and re-ligation of the released DNA.

Evolution

Further information: RNA world hypothesis

DNA contains the genetic information that allows all modern living things to function, grow and reproduce. However, it is unclear how long in the 4-billion-year history of life DNA has performed this function, as it has been proposed that the earliest forms of life may have used RNA as their genetic material. RNA may have acted as the central part of early cell metabolism as it can both transmit genetic information and carry out catalysis as part of ribozymes. This ancient RNA world where nucleic acid would have been used for both catalysis and genetics may have influenced the evolution of the current genetic code based on four nucleotide bases. This would occur, since the number of different bases in such an organism is a trade-off between a small number of bases increasing replication accuracy and a large number of bases increasing the catalytic efficiency of ribozymes.

However, there is no direct evidence of ancient genetic systems, as recovery of DNA from most fossils is impossible. This is because DNA will survive in the environment for less than one million years and slowly degrades into short fragments in solution. Claims for older DNA have been made, most notably a report of the isolation of a viable bacterium from a salt crystal 250 million years old, but these claims are controversial.

On 8 August 2011, a report, based on NASA studies with meteorites found on Earth, was published suggesting building blocks of DNA (adenine, guanine and related organic molecules) may have been formed extraterrestrially in outer space.

Uses in technology

Genetic engineering

Further information: Molecular biology, nucleic acid methods and genetic engineering

Methods have been developed to purify DNA from organisms, such as phenol-chloroform extraction, and to manipulate it in the laboratory, such as restriction digests and the polymerase chain reaction. Modern biology and biochemistry make intensive use of these techniques in recombinant DNA technology. Recombinant DNA is a man-made DNA sequence that has been assembled from other DNA sequences. They can be transformed into organisms in the form of plasmids or in the appropriate format, by using a viral vector. The genetically modified organisms produced can be used to produce products such as recombinant proteins, used in medical research, or be grown in agriculture.

Forensics

Further information: DNA profiling

Forensic scientists can use DNA in blood, semen, skin, saliva or hair found at a crime scene to identify a matching DNA of an individual, such as a perpetrator. This process is formally termed DNA profiling, but may also be called "genetic fingerprinting". In DNA profiling, the lengths of variable sections of repetitive DNA, such as short tandem repeats and minisatellites, are compared between people. This method is usually an extremely reliable technique for identifying a matching DNA. However, identification can be complicated if the scene is contaminated with DNA from several people. DNA profiling was developed in 1984 by British geneticist Sir Alec Jeffreys, and first used in forensic science to convict Colin Pitchfork in the 1988 Enderby murders case.

The development of forensic science, and the ability to now obtain genetic matching on minute samples of blood, skin, saliva or hair has led to a re-examination of a number of cases. Evidence can now be uncovered that was not scientifically possible at the time of the original examination. Combined with the removal of the double jeopardy law in some places, this can allow cases to be reopened where previous trials have failed to produce sufficient evidence to convince a jury. People charged with serious crimes may be required to provide a sample of DNA for matching purposes. The most obvious defence to DNA matches obtained forensically is to claim that cross-contamination of evidence has taken place. This has resulted in meticulous strict handling procedures with new cases of serious crime. DNA profiling is also be used to identify victims of mass casualty incidents. As well as positively identifying bodies or body parts in serious accidents, DNA profiling is being successfully used to identify individual victims in mass war graves – matching to family members.

Bioinformatics

Further information: Bioinformatics

Bioinformatics involves the manipulation, searching, and data mining of biological data, and this includes DNA sequence data. The development of techniques to store and search DNA sequences have led to widely applied advances in computer science, especially string searching algorithms, machine learning and database theory. String searching or matching algorithms, which find an occurrence of a sequence of letters inside a larger sequence of letters, were developed to search for specific sequences of nucleotides. The DNA sequence may be aligned with other DNA sequences to identify homologous sequences and locate the specific mutations that make them distinct. These techniques, especially multiple sequence alignment, are used in studying phylogenetic relationships and protein function. Data sets representing entire genomes' worth of DNA sequences, such as those produced by the Human Genome Project, are difficult to use without the annotations that identify the locations of genes and regulatory elements on each chromosome. Regions of DNA sequence that have the characteristic patterns associated with protein- or RNA-coding genes can be identified by gene finding algorithms, which allow researchers to predict the presence of particular gene products and their possible functions in an organism even before they have been isolated experimentally. Entire genomes may also be compared which can shed light on the evolutionary history of particular organism and permit the examination of complex evolutionary events.

DNA nanotechnology

The DNA structure at left (schematic shown) will self-assemble into the structure visualized by atomic force microscopy at right. DNA nanotechnology is the field that seeks to design nanoscale structures using the molecular recognition properties of DNA molecules. Image from Strong, 2004.

Further information: DNA nanotechnology

DNA nanotechnology uses the unique molecular recognition properties of DNA and other nucleic acids to create self-assembling branched DNA complexes with useful properties. DNA is thus used as a structural material rather than as a carrier of biological information. This has led to the creation of two-dimensional periodic lattices (both tile-based as well as using the "DNA origami" method) as well as three-dimensional structures in the shapes of polyhedra. Nanomechanical devices and algorithmic self-assembly have also been demonstrated, and these DNA structures have been used to template the arrangement of other molecules such as gold nanoparticles and streptavidin proteins.

History and anthropology

Further information: Phylogenetics and Genetic genealogy

Because DNA collects mutations over time, which are then inherited, it contains historical information, and, by comparing DNA sequences, geneticists can infer the evolutionary history of organisms, their phylogeny. This field of phylogenetics is a powerful tool in evolutionary biology. If DNA sequences within a species are compared, population geneticists can learn the history of particular populations. This can be used in studies ranging from ecological genetics to anthropology; For example, DNA evidence is being used to try to identify the Ten Lost Tribes of Israel.

DNA has also been used to look at modern family relationships, such as establishing family relationships between the descendants of Sally Hemings and Thomas Jefferson. This usage is closely related to the use of DNA in criminal investigations detailed above. Indeed, some criminal investigations have been solved when DNA from crime scenes has matched relatives of the guilty individual.

History of DNA research

Further information: History of molecular biology

James D. Watson and Francis Crick (right), co-originators of the double-helix model, with Maclyn McCarty (left).

DNA was first isolated by the Swiss physician Friedrich Miescher who, in 1869, discovered a microscopic substance in the pus of discarded surgical bandages. As it resided in the nuclei of cells, he called it "nuclein". In 1878, Albrecht Kossel isolated the non-protein component of "nuclein", nucleic acid, and later isolated its five primary nucleobases. In 1919, Phoebus Levene identified the base, sugar and phosphate nucleotide unit. Levene suggested that DNA consisted of a string of nucleotide units linked together through the phosphate groups. However, Levene thought the chain was short and the bases repeated in a fixed order. In 1937 William Astbury produced the first X-ray diffraction patterns that showed that DNA had a regular structure.

In 1927 Nikolai Koltsov proposed that inherited traits would be inherited via a "giant hereditary molecule" made up of "two mirror strands that would replicate in a semi-conservative fashion using each strand as a template". In 1928, Frederick Griffith discovered that traits of the "smooth" form of Pneumococcus could be transferred to the "rough" form of the same bacteria by mixing killed "smooth" bacteria with the live "rough" form. This system provided the first clear suggestion that DNA carries genetic information—the Avery–MacLeod–McCarty experiment—when Oswald Avery, along with coworkers Colin MacLeod and Maclyn McCarty, identified DNA as the transforming principle in 1943. DNA's role in heredity was confirmed in 1952, when Alfred Hershey and Martha Chase in the Hershey–Chase experiment showed that DNA is the genetic material of the T2 phage.

In 1953, James D. Watson and Francis Crick suggested what is now accepted as the first correct double-helix model of DNA structure in the journal Nature. Their double-helix, molecular model of DNA was then based on a single X-ray diffraction image (labeled as "Photo 51") taken by Rosalind Franklin and Raymond Gosling in May 1952, as well as the information that the DNA bases are paired — also obtained through private communications from Erwin Chargaff in the previous years. Chargaff's rules played a very important role in establishing double-helix configurations for B-DNA as well as A-DNA.

Experimental evidence supporting the Watson and Crick model was published in a series of five articles in the same issue of Nature. Of these, Franklin and Gosling's paper was the first publication of their own X-ray diffraction data and original analysis method that partially supported the Watson and Crick model; this issue also contained an article on DNA structure by Maurice Wilkins and two of his colleagues, whose analysis and in vivo B-DNA X-ray patterns also supported the presence in vivo of the double-helical DNA configurations as proposed by Crick and Watson for their double-helix molecular model of DNA in the previous two pages of Nature. In 1962, after Franklin's death, Watson, Crick, and Wilkins jointly received the Nobel Prize in Physiology or Medicine. Nobel Prizes were awarded only to living recipients at the time. A debate continues about who should receive credit for the discovery.

In an influential presentation in 1957, Crick laid out the central dogma of molecular biology, which foretold the relationship between DNA, RNA, and proteins, and articulated the "adaptor hypothesis". Final confirmation of the replication mechanism that was implied by the double-helical structure followed in 1958 through the Meselson–Stahl experiment. Further work by Crick and coworkers showed that the genetic code was based on non-overlapping triplets of bases, called codons, allowing Har Gobind Khorana, Robert W. Holley and Marshall Warren Nirenberg to decipher the genetic code. These findings represent the birth of molecular biology.

See also

• Crystallography
• DNA error
• DNA microarray
• DNA sequencing
• Genetic disorder
• Nucleic acid modeling
• Nucleic acid notation
• Phosphoramidite
• Southern blot
• Triple-stranded DNA
• X-ray scattering techniques
• Nucleic acid double helix
• DNA-encoded chemical library

References

Further reading

• Berry, Andrew; Watson, James D. (2003). DNA: the secret of life. New York: Alfred A. Knopf. ISBN 0-375-41546-7. 
• Calladine, Chris R.; Drew, Horace R.; Luisi, Ben F. and Travers, Andrew A. (2003). Understanding DNA: the molecule & how it works. Amsterdam: Elsevier Academic Press. ISBN 0-12-155089-3. 
• Dennis, Carina; Julie Clayton (2003). 50 years of DNA. Basingstoke: Palgrave Macmillan. ISBN 1-4039-1479-6. 
• Judson, Horace F. 1979. The Eighth Day of Creation: Makers of the Revolution in Biology. Touchstone Books, ISBN 0-671-22540-5. 2nd edition: Cold Spring Harbor Laboratory Press, 1996 paperback: ISBN 0-87969-478-5.
• Olby, Robert C. (1994). The path to the double helix: the discovery of DNA. New York: Dover Publications. ISBN 0-486-68117-3. , first published in October 1974 by MacMillan, with foreword by Francis Crick;the definitive DNA textbook,revised in 1994 with a 9 page postscript
• Micklas, David. 2003. DNA Science: A First Course. Cold Spring Harbor Press: ISBN 978-0-87969-636-8
• Ridley, Matt (2006). Francis Crick: discoverer of the genetic code. Ashland, OH: Eminent Lives, Atlas Books. ISBN 0-06-082333-X. 
• Olby, Robert C. (2009). Francis Crick: A Biography. Plainview, N.Y: Cold Spring Harbor Laboratory Press. ISBN 0-87969-798-9. 
• Rosenfeld, Israel. 2010. DNA: A Graphic Guide to the Molecule that Shook the World. Columbia University Press: ISBN 978-0-231-14271-7
• Schultz, Mark and Zander Cannon. 2009. The Stuff of Life: A Graphic Guide to Genetics and DNA. Hill and Wang: ISBN 0-8090-8947-5
• Stent, Gunther Siegmund; Watson, James D. (1980). The double helix: a personal account of the discovery of the structure of DNA. New York: Norton. ISBN 0-393-95075-1. 
• Watson, James D. 2004. DNA: The Secret of Life. Random House: ISBN 978-0-09-945184-6
• Wilkins, Maurice (2003). The third man of the double helix the autobiography of Maurice Wilkins. Cambridge, Eng: University Press. ISBN 0-19-860665-6. 

External links

Listen to this article (info/dl)

This audio file was created from a revision of the "DNA" article dated 2007-02-12, and does not reflect subsequent edits to the article. (Audio help)

More spoken articles

• DNA at the Open Directory Project
• DNA binding site prediction on protein
• DNA the Double Helix Game From the official Nobel Prize web site
• DNA under electron microscope
• Dolan DNA Learning Center
• Double Helix: 50 years of DNA, Nature
• Proteopedia DNA
• Double Helix 1953–2003 National Centre for Biotechnology Education
• Francis Crick and James Watson talking on the BBC in 1962, 1972, and 1974
• Genetic Education Modules for Teachers—DNA from the Beginning Study Guide
• Olby R (2003). "Quiet debut for the double helix". Nature 421 (6921): 402–5. doi:10.1038/nature01397. PMID 12540907. 
• DNA from the Beginning Another DNA Learning Center site on DNA, genes, and heredity from Mendel to the human genome project.
• PDB Molecule of the Month pdb23_1
• Rosalind Franklin's contributions to the study of DNA
• The Register of Francis Crick Personal Papers 1938 – 2007 at Mandeville Special Collections Library, University of California, San Diego
• U.S. National DNA Day—watch videos and participate in real-time chat with top scientists
• Clue to chemistry of heredity found The New York Times June 1953. First American newspaper coverage of the discovery of the DNA structure

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 分子遺伝学の原理 principles of molecular genetics
• 2. 次世代DNAシークエンシング（NGS）：原理および臨床応用 next generation dna sequencing ngs principles and clinical applications
• 3. 2本鎖（ds）DNA、Sm、およびU1 RNPに対する抗体 antibodies to double stranded ds dna sm and u1 rnp
• 4. エピジェネティクスの原理 principles of epigenetics
• 5. ミトコンドリアの構造、機能、および遺伝学 mitochondrial structure function and genetics

English Journal

• Doxorubicin-induced cardiac dysfunction is attenuated by ciclosporin treatment in mice through improvements in mitochondrial bioenergetics.

• Marechal X, Montaigne D, Marciniak C, Marchetti P, Hassoun SM, Beauvillain JC, Lancel S, Neviere R.Source*Department of Physiology (EA 4484), Faculty of Medicine, University of the North of France, place de Verdun, Lille cedex 59045, France.
• Clinical science (London, England : 1979).Clin Sci (Lond).2011 Nov 1;121(9):405-13.
• We tested whether inhibition of mitochondrial membrane potential dissipation by CsA (ciclosporin A) would prevent doxorubicin-induced myocardial and mitochondrial dysfunction. Acute and subchronic models of doxorubicin exposition were performed in mice with either a single intraperitoneal bolus (10?
• PMID 21605084

• Peptide biomarkers as a way to determine meat authenticity.

• Sentandreu MA, Sentandreu E.AbstractMeat fraud implies many illegal procedures affecting the composition of meat and meat products, something that is commonly done with the aim to increase profit. These practices need to be controlled by legal authorities by means of robust, accurate and sensitive methodologies capable to assure that fraudulent or accidental mislabelling does not arise. Common strategies traditionally used to assess meat authenticity have been based on methods such as chemometric analysis of a large set of data analysis, immunoassays or DNA analysis. The identification of peptide biomarkers specific of a particular meat species, tissue or ingredient by proteomic technologies constitutes an interesting and promising alternative to existing methodologies due to its high discriminating power, robustness and sensitivity. The possibility to develop standardized protein extraction protocols, together with the considerably higher resistance of peptide sequences to food processing as compared to DNA sequences, would overcome some of the limitations currently existing for quantitative determinations of highly processed food samples. The use of routine mass spectrometry equipment would make the technology suitable for control laboratories.
• Meat science.Meat Sci.2011 Nov;89(3):280-5. Epub 2011 May 7.
• Meat fraud implies many illegal procedures affecting the composition of meat and meat products, something that is commonly done with the aim to increase profit. These practices need to be controlled by legal authorities by means of robust, accurate and sensitive methodologies capable to assure that
• PMID 21612878

Japanese Journal

• Preemptive therapy of human herpesvirus-6 encephalitis with foscarnet sodium for high-risk patients after hematopoietic SCT

• Ishiyama Ken,Katagiri Takamasa,Hoshino Takumi,Yoshida Takashi,Yamaguchi Masaki,Nakao Shinji
• Bone Marrow Transplantation 46(6), 863-869, 2011-06-30
• … Plasma HHV-6 DNA was measured thrice weekly from day 7 until day 36 after umbilical cord blood transplantation (UCBT) or HSCT from HLA-haploidentical relatives. … PFA, 90 mg/kg/day, was started when HHV-6 DNA exceeded 5 × 102 copies/mL. … Twelve of 15 UCBT recipients became positive for HHV-6 DNAemia, defined by greater than 1 × 102 copies/mL of HHV-6 DNA in plasma. …
• NAID 120002439396

• Valine 1532 of human BRC repeat 4 plays an important role in the interaction between BRCA2 and RAD51

• Ochiai Kazuhiko,Yoshikawa Yasunaga,Yoshimatsu Kumiko,Oonuma Toshina,Tomioka Yukiko,Takeda Eichi,Arikawa Jiro,Mominoki Katsumi,Omi Toshinori,Hashizume Kazuyoshi,Morimatsu Masami
• FEBS Letters 585(12), 1771-1777, 2011-06-23
• … The breast cancer susceptibility protein BRCA2 is essential for recombinational DNA repair. … BRCA2 specifically binds to RAD51 via 8 BRC repeat motifs and delivers RAD51 to double-stranded DNA breaks. …
• NAID 120003089243

Related Links

• デオキシリボ核酸 - Wikipedia

ミーシャー（スイス）がDNAを発見、1871年にヌクレインという名で発表したが、彼は その役割を細胞内におけるリンの貯蔵と考えていた。（後にリヒャルト・アルトマン（ ドイツ）によってヌクレインは核酸と改称される） ...

Related Pictures

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★リンクテーブル★

国試過去問	「099D034」「095B017」「105C015」
リンク元	「100Cases 27」「100Cases 34」「核酸」「RNA」「ヌクレオチド配列」
拡張検索	「DNAヌクレオチジルトランスフェラーゼ」「DNA replication」「DNA塩基配列」
関連記事	「D」

「099D034」

　　[★]

• ダイオキシンについて誤っているのはどれか。

• a. 発癌性を持つ。
• b. タバコの煙に含まれる。
• c. DNAを直接損傷する。
• d. 母乳を介して新生児に移行する。
• e. 環境中の濃度は法律で規制されている。

[正答]

C

※国試ナビ4※　［099D033］←［国試_099］→［099D035］

「095B017」

　　[★]

• 肺炎球菌性肺炎の病因診断に有用なのはどれか。

• (1)　喀痰のDNA診断
• (2)　喀痰のGram染色
• (3)　血液培養
• (4)　血清抗体価測定
• (5)　尿中抗体価測定

• a. (1)(2)
• b. (1)(5)
• c. (2)(3)
• d. (3)(4)
• e. (4)(5)

[正答]

C

※国試ナビ4※　［095B016］←［国試_095］→［095B018］

「105C015」

　　[★]

• DNAの三次元立体構造と役割の解明に貢献したのは誰か。

• a　Charles R Darwin
• b　Barbara McClintock
• c　Gregor J Mendel
• d　Jacques L Monod
• e　James D Watson

[正答]

E

※国試ナビ4※　［105C014］←［国試_105］→［105C016］

「100Cases 27」

　　[★]

☆case27　関節痛

■症例

37歳　女性

主訴：関節痛

現病歴：数ヶ月、膝の痛みがだんだん強くなっていると感じていた。痛みは手や足の小関節に多く、朝歩くときに最もこわばる。痛みはジクロフェナクを飲むと和らぐ。そのほかの症状として疲労感を感じ、最近、体重が３ヶ月で４ｋｇ減っている。

喫煙歴：なし。

飲酒歴：機会飲酒

既往歴：なし

家族歴：既婚、子供は２人

服薬歴：ジクロフェナク

職業歴：legal sevretary

身体所見 examination

　顔貌　青白、臨床的な貧血を認める。近位指節間関節・中手指節関節　腫脹・effusionを伴う疼痛。中足趾節関節　圧痛。それ以外は正常。

検査　investigation

　血液検査

　　Hb低下

　　ESR上昇

　　尿素軽度上昇

　　クレアチニン軽度上昇

　　正常：白血球、MCV、血小板、ナトリウム、カリウム、グルコース、アルブミン

　尿検査

　　蛋白(-)、尿糖(-)、潜血(-)、

■問題

　本症例では診断とその根拠を考えるのは簡単なので、鑑別疾患をあげてその疾患に特徴的な症候を列挙しましょう。

■関節痛 DIF.283

　V Vascular

　　血友病 hemophilia　血友病性関節症(急性：疼痛、腫脹、熱感(SOR.241)

慢性：可動域の低下、変形、関節周囲筋萎縮(SOR.241))。家族歴

　　壊血病 scurvy　。生活環境。食事歴

　　無菌性骨壊死 aseptic bone necrosis (Osgood-Schlatter diseaseとか)

　I Inflammatory

　　感染性関節炎(細菌性関節炎(化膿性関節炎・淋菌性関節炎・結核性関節炎・嫌気性菌関節炎 )、真菌性関節炎、スピロヘータ関節炎(梅毒性関節炎・ライム関節炎)、マイコプラズマ関節炎、ウイルス性関節炎)

　N Neoplastic disorders

　　骨原性肉腫 osteogenic sarcoma

　　巨細胞腫 giant cell tumors

　D Degenerative disorders

　　degenerative joint disease

　　変形性関節症 osteoarthritis

　I Intoxication

　　痛風 gout (uric acid)

　　偽痛風 pseudogout (calcium pyrophosphate)

　　ループス症候群 lupus syndrome of hydralazine (Apresoline) and procainamide

　　gout syndrome of diuretics

　C Congenital and acquired malformations bring to mind the joint deformities of tabes dorsalis and syringomyelia and congenital dislocation of the hip. Alkaptonuria is also considered here.

　A Autoimmune indicates

　　関節リウマチ RA

　　血清病 serum sickness

　　全身性エリテマトーデス lupus erythematosus

　　リウマチ熱 rheumatic fever

　　ライター症候群 Reiter syndrome

　　潰瘍性大腸炎 ulcerative colitis

　　クローン病=限局性回腸炎 regional ileitis

　　乾癬性関節炎 psoriatic arthritis

　　リウマチ性多発筋痛症 polymyalgia rheumatica

　T Trauma

　E Endcrine

　　先端肥大症 acromegaly

　　閉経 menopause

　　糖尿病 diabetes mellitus

■関節炎の分類

・炎症部位の数

　単関節炎：痛風、偽痛風、離断性骨軟骨炎、血行性の化膿性関節炎のほとんど

　多関節炎：リウマチ性疾患、ウイルス性疾患、白血病での関節症状、易感染性宿主における血行性の化膿性関節炎

■関節リウマチ

　診断基準

　関節症状

　　朝のこわばり、疼痛、腫脹、関節の動揺、関節可動域制限、変形(手指、足趾、膝関節)。(SOR.211)

　　手指の近位指節間関節(PIP関節)、中手指節関節(MP関節)。遠位指節間関節(DIP関節)に初発することは稀。(SOR.211)

　　左右対称性に生じることが多い。手関節、足趾、膝関節に初発する。(SOR.211)

　関節外症状

　　全身症状：発熱

　　皮膚症状：リウマトイド結節(肘の伸側、後頭部、手指)

　　眼症状：上胸膜炎(10日の経過で治癒)、強膜炎(予後不良)。稀に角膜穿孔

　　血液障害：(高頻度)貧血、白血球減少(Felty病。DMARDs投与中の場合は薬剤性の骨髄抑制を考慮)

　　アミロイドーシス：ネフローゼや下痢を来した症例で疑う。アミロイド蛋白はAA

　　腎障害：稀。アミロイドーシスの続発症か薬剤性を考慮。

　　呼吸器症状：間質性肺炎の合併多い。下肺野に好発。通常無症状。メトトレキセートなどの使用により薬剤性の急性間質性肺炎を生じることがある。

　　心・血管障害：リンパ管炎による難治性の浮腫。

　　神経症状：環軸関節亜脱臼により項部痛や脊髄症上が出現しうる。

　　骨粗鬆症

　　腱鞘滑膜炎：手指、手関節、足関節

■両側性多関節炎の鑑別疾患

　OA：遠位指節間関節を冒すのが特徴的で、近位指節間関節、中手指節関節を冒しうる。

　RA：

　SLE：軽度、症状の程度が変動する非びらん性の関節炎

　gout：単関節炎からはじまる。

　血清陰性関節炎：強直性脊椎炎、感染、ライター病：中～大関節に非対称性の関節炎。仙腸関節と遠位指節間関節にも関節炎

　急性ウイルス性関節炎：風疹。

■KEY POINTS

・RAでは遠位指節間関節は冒されない傾向がある。

・RAの全身症状は関節症状に先行することがある。

・RAの活動性と貧血及びESRは相関している。

・NSAIDsは腎機能に悪影響を与えることがある。

■initial plan

　Dx 1. 単純X線写真

　　　　・亜脱臼、関節周囲の骨萎縮(傍関節性骨骨粗鬆症,juxta-articular osteoporosis)、関節裂隙の狭小化、関節辺縁のびらん(bony erosion)

　　　　　・初期のRAで第5趾に骨びらんが一般的に見られる。

　　　　・血液検査

　　　　　・RF、抗DNA抗体

　Tx 1. 鎮痛薬

　　　　・NSAIDs：鎮痛とこわばりの軽減

　　 2. DMARDs(メトトレキセート、レフルノミド、金製剤、ペニシラミン)

　　　　・NSAIDsで症状が治まらない場合に考慮

　　 3. 抗TNF抗体

　　　　・重症のRAで効果がある場合がある。

■参考文献

SOR　標準整形外科学 第10版 医学書院

DIF　Differential Diagnosis in Primary Care Fourth Edition版 Lippincott Williams & Wilkins

「100Cases 34」

　　[★]

☆case34　てんかん発作

■症例

23歳　アフリカ-カリブ系　女性　銀行の店員

主訴：てんかん発作

現病歴：強直間代発作を2回起こしたところを母親が目撃していた。娘の行動は次第におかしくなり、また娘は自分のことを話している声が聞こえていた(幻聴)。最近、頭痛を訴えていた。体重が減少し、脱毛があった。盗汗と主に足と手の小関節に及ぶflitting 関節痛を訴えていた。服用薬なし。タバコ1日5-10本、アルコール10 unit/week(缶ビール(350ml)6本弱)

既往歴：特記なし(medical or psychiatric history)

家族歴：

生活歴：

・身体診断

意識：眠そうだが痛みに反応。頚部硬直：なし。頭髪：薄く斑状。体温38.5℃。リンパ節：たくさんの部位で触知。

心拍：104/分、整。血圧：164/102 mmHg。心血管系、呼吸器系、腹部：異常なし。

神経所見：focal anormalityなし(局所性異常)。乳頭浮腫：認めず。

・検査

(血液生化学)

上昇：erythrocyte sedimentation rate、urea、creatinine

低下：hemoglobin、white cell count、platelet

正常：mean corpuscular volume、sodium、potassium、glucose

(腰椎穿刺)

上昇：leukocytes、CSF protein

正常：CSF glucose

(尿検査)

蛋白：＋＋＋。血尿：＋＋＋。赤血球：＋＋。赤血球円柱：あり。

(その他)

胸部X線：異常なし。ECG：洞性頻脈。頭部CT：正常。CSFグラム染色：陰性(光顕レベルで細菌なし)

■glossary

fall out　(毛髪などが)抜ける

night sweat 盗汗、寝汗

tonic-clonic generalized seizure 全般性強直間代発作

flit　vi (鳥・蝶など)すいすい/ひらひら飛ぶ、飛び回る、飛翔する。(人が)軽やかに通る、行き交う。(時が)(飛ぶように)すぎる。(幻想など)去来する、よぎる、(表情が)かすめる

drowsy　adj. 眠い。眠そうな。眠気を誘う。ものうい。眠ったような

stiffness　n. 堅いこと、堅ぐるしさ、がんこさ

delirium tremens 振戦譫妄

hypertensive encephalopathy 高血圧性脳症

alopecia　脱毛症

African-Caribbean アフリカ-カリブ系

fit n.　(病気の)発作。引きつけ、痙攣。(感情の)激発、一時的興奮、気まぐれ

chorea n. 舞踏病

recreational drug 耽溺性があり乱用される脱法薬物

urgent adj. (物・事が)急を要する、緊急の、背拍質(pressing)。(～を)緊急に必要とする(in)。(S is ～ (with O1) for [in] O2)(人が)(O1(人)に)O2(物・事)をしつこく求める。(人に/～するように)催促する(for/to do)。(要求などが)執拗な。

□てんかん発作

・新規発生したてんかん発作の原因(ICU.805-806)

・薬物中毒(テオフィリンなど)

・薬物からの離脱(アルコールなど)

・感染症(髄膜炎、膿瘍など)

・頭部外傷

・虚血障害(虚血あるいはびまん性)

・占拠性病変(腫瘍あるいは血腫)

・代謝性障害(肝性脳症、尿毒症性脳症、敗血症、低血糖、低ナトリウム血症、低カルシウム血症など)

・合併症(ICU.805-806)

・全身性てんかん発作の場合：高血圧、乳酸アシドーシス、高体温、呼吸障害、誤嚥、肺水腫、横紋筋融解、自傷、不可逆性の神経学的障害(30分間以上てんかん発作が持続した場合)

■可能性の高い診断

　全身性エリテマトーデス systemic lupus erythematosus(SLE)

■鑑別診断のポイント

　自己免疫疾患は多彩な症状を示す。そのため、個々の症状に着目して鑑別診断をあげるのではなく、症状や検査値の異常を総合的に見て判断する必要がある。

■解答

　(第1パラグラフ)SLEの病態

精神症状：(SLEは脳で血管炎を呈することで生じる)うつ(depression)、統合失調症様の精神病、痙攣(fits)、舞踏病(chorea)、脳梗塞/脊髄梗塞

脳脊髄液：白血球増多(leukopenia)、蛋白増加

血液：自己免疫性溶血貧血(Coombs'-positive hemolytic anemia)がありうる。白血球減少と血小板減少症は普通にみられる。

腎症状：ループス腎炎は普通に見られ、顕微鏡的血尿・タンパク尿、ネフローゼ、あるいは腎不全が現れるかもしれない。

関節症状：変形を伴わない関節痛(PIP関節(近位指節間関節)、MP関節(中手指節関節)、手関節)

　(第2パラグラフ)SLEの確定診断のための検査・治療

　・すぐにすべきことは降圧薬、抗痙攣薬の投与

　・確定診断のために次の検査を行っていく(もっとも、症例の提示された所見で(日本の？)SLEの診断基準を満たすけど)

　　・検疫血清検査：抗DNA抗体、C3、C4

　　・腎生検：ループス腎炎の程度を把握

　・治療：活動性の感染がないことを確認　←　薬物療法ではステロイドや免疫抑制薬を使うため

　　・ステロイド静脈内投与、あるいはシクロホスファミドなどの細胞毒性薬(cytotoxic agents)の投与

　　・重症、治療抵抗性だったら血漿交換を行う。

■鑑別診断　頭痛/精神病的様態(psychiatric features)/痙攣

・髄膜炎、脳炎

・レクリエーショナルドラッグの中毒(例えばコカイン)

・脳腫瘍

・急性のアルコール禁断症状：振戦譫妄

・高血圧脳症

■KEYPOINT

・SLEは特に若いアフリカ系-カリブ系に普通に一般的

・SLEでは主に神経症状と精神症状をを伴って現れることがある

・白血球低下と血小板の低下はしばしばSLEを示唆する

□tonic-clonic seizure 強直間代発作

　意識消失とともに全身の随意筋に強直痙攣が生じ(強直痙攣期tonic convulsion)、次いで全身の筋の強直と弛緩とが律動的に繰り返される時期(間代痙攣期clonic convulsion)を経て、発作後もうろう状態を呈する一連の発作。

□350ml アルコール5%

350x0.05/10=1.75 unit

□細胞毒性薬

　免疫抑制薬や抗腫瘍薬として用いられる。

antimetabolites

アザチオプリン azathioprine

メトトレキセート methotrexate

ミコフェノール酸 mycophenolic acid, ミコフェノール酸モフェチル mycophenolate mofetil

レフルノミド leflunomide

alkylating agents

シクロホスファミド cyclophosphamide

「核酸」

　　[★]

英

nucleic acid

関

ヌクレオチド

• DNAとRNAを指す
• ホスホジエステル結合で鎖状に連結している

「RNA」

　　[★]

同

リボ核酸 ribonucleic acid RNA

関

DNA

• D-リボースを糖成分とする核酸

　

「ヌクレオチド配列」

　　[★]

英

nucleotide sequence

同

塩基配列、base sequence

関

DNA、RNA

「DNAヌクレオチジルトランスフェラーゼ」

　　[★]

英

DNA nucleotidyltransferase

関

DNAポリメラーゼ

「DNA replication」

　　[★]

• DNA複製

関

autonomous replication

「DNA塩基配列」

　　[★]

英

DNA sequence

関

DNA配列

「D」

　　[★]

• アスパラギン酸
• ジヒドロウリジン
• 遠位の distal,
• うつ病 depression
• 下行結腸 descending colon(大腸内視鏡検査の結果を記載するときに用いる)