生物信息学：第五章　多序列比对

??c ? 1 5.1?y ?? 1 ^? s￥$b?7
??yEB￥?F￥?  ? a
á ì1 y ??? -W￥1"
?"??￡ U??yEB￥+?b?? V[4ú? 1￥? .1
? 1? üBFM1? ￥×1 3tD TZ ?"M?×1￥T¨b'c?
 á ì|o B" ? 1￥ZE
V?? m?￥Z T?<W?¨￥9 ???
' ?ì 1?1￥ZEb 5.2? 1￥il ? 1μ H¨ ?usBF? -W￥μs
??1¨? í ?BF? -W￥M ??1"
[LB?yEB￥+?μB?e ü21￥ 3bD ?? 1B"
?  1￥ZEy ?? ?D 3tD?- byN
??á ì?? ?? 1￥2T¤ o??pp￥e?2 ?B"
? 1￥2T9 àμ '??? 'p-s
7 o?a1 ? P¨￥?v? Q? ? -W￥M ??1"[# ? ì￥ 3tD+?b A?
? 131 P¨? ê￥sy b" BtXü<W P¨iˉ?? ?é￥? 9 ????
?31μB? 7?ZL L¨￥? 1 myI y b V[V??]??y? 1?b? ú
?1·y ?1?￥ 3tD $
7?? ^ 8￥1ZE
?1?1 m?1?b"-
y? 1?￥ ZEv8 V[s1 v ?b?B ? ^?? ??￥M ??
?t??éa?-W￥ V lM??b 6B ?ZE5?1 ?¨?aés0￥=)2??)2?
9ü ^ a? ? ￥ú)2+???12TbA?
? ?ZE ?¤2T V?μ?vμYbB? a ?
 ?4?'?ZE ?¤2TB???
?? a
 ? ìV?]?Q??aé? ? ?c￥ 3tD?b ?? ???2?￥1? ^dè×1￥1?
? ? ì?μ? VE ? ￥ K?
y1? ?ZE?????Q??aés0 ?z{￥???bá ì??
?a é?  ^üV DNA ?  cJr¤?￥bV? ?￥? A
 ???D DNA s0 ?z{ ￥?÷1o¤ípb7?aé2" ? ' &{ ?￥??
? ?üVJraFy? e ?9F￥2?
 ??￥? e
s0W￥MoT¨?
K???×?￥???aé 2byN
?9 ^????  ? 1ZE??￥?1eybA?
?T? ?¨2  ? 
?? 1íPμ?vúùb??￥ ^
Dv ￥?  ? M1
 L?¤￥? aé??2 ?  L ¤ V ?bv ?f ?/
i àμ2 ?  V[ ?¨
á ìo?G L? ￥M ???Bt 3t?D+?y ?B?1? ?i￥? 1?b 5.3 ? 1￥?l 1 L? í ?
á ì? 1V?ó/ ?￥?lbü? 1 ATBf =?V
V? ?B?}VB?? 
 ?B }VB??￥ê?b|? Gv/ ? 5A?V?

a
B??  ?μ?￥Mê???M

b
|?]? WM] M ?￥?b?]B 
'D V?|? WM]M ?? / bá ì?1- ? ??￥ê?1 'ê?b?? ú￥? 3ê￥? ^?? ? G
5 'ê?ú 3 ü ^?? ?
7??M??? ?? ?bM?1
á ì?1a? ??￥ê ?1Mê?bA?
]B ? ?μ?￥Mê?M]
7 ???￥ 'ê?? ]
y1 ? ì ?1?]￥? b31 a ü￥ ^
 'ê? ^? ' &%μ￥ ??
 ? a ^1-￥ê?
7Mê?5 ^üV1a￥ê?
9ü1V??í ?￥ ? ?b
5.4 ???  ? 1￥K?2T V[¨B???? 
consensus
V U
μ H9?LX? 
pseudo-sequence

YèF1a ?μ? ￥/ ?b?B??? ￥? ^??￥] B ?B,7¤?b ??? o ^? 12T￥B?V UZ Tb? V[¨?× ? ?V U12T
? / ?|1o ￥? ?ZEb7 BLOCKS ?  o5 ^s12T? àμ bêC￥ o  v

iü ? ì??ê?+s?s ? ?b7 PRINTS ?  o5¨|yZEV12T ?s ?μ àμ bê￥? 8
éB??
iGNy ?B?dF?￥s ? ?b? tZE? 3c?? 8c?sYí[W%) ?b 5.5 ?Eˉ? ? 1￥9 ? M? V4
yNμA1s[// ?￥ˉ?b ?? 1 ?3 1￥9 ? HW?=i bWD? ?? ￥éμ1
? a?1?? ?? é￥e
 ¨ O
m 1 m 2
V Ub? m 1 am 2 ^· H? ￥éb?? 15 V[ ?31| ??  1￥ ? bW ?Z???
'eμ=?ü ? 9FBHUSàb?" ?Eˉ?üM?  O
m 1 m 2 m 3

? m 3 V U??H? ￥éb ?"?  ? ￥9F
 ?Eˉ?9?9Fbá ì¨ O
m 1 m 2 m 3 …m n
V U n? ? é?1 H￥ ?Eˉ?
? m n ^KaBH? ￥éb?? éMμ?v
5 Ve?? O
m n

? nV U? ￥ ?"
 mV U? ￥ébA?
 ?"?  ? ￥9 F
? 1￥ ?Eˉ??· ?? p9éb ?? ?Eˉ?
 ^ù?? 1￥B?×1Z ?b1N
á 3 ? ?μ L¨i l￥? 1 ?Eb?tZE￥+? ^ ?¨? T
heuristics
 ?E?? ?Eˉ?
[ ¤B??1 ?i?i?B? ^Ka￥12T
¨ ?s0? ayé? ?a°s o ? ? e
[#é? ?
clustering
s?bμ￥ ?E|? ?????? ?E2 ? ?b è?
 ?μ￥? é?  1
| ?μ￥? D?+?￥? é?1
? ?ó?￥T÷ ?é?sF1
??bA?·
  ?ZEp¤￥2TYè? ^Ka3
 à 31üV n-1Q ?? 1
? n1?D1￥? ? ?b 5.6 my1ZE my1ZEóD?üè A?by14 ?F?Bt?4y í
 my1Yè$a1 μ?v￥ ?i?b L
' P¨9 ???é?1?1
 ?¤2T?￥? ??9??í[ - jb?üV? ki μ1?ú￥ V?￥9 ???$ 
2? L2TóD' 
? 12Té? my? e
?? a ^dèA1￥b ? 1￥èqXüμ?
?Bt{μI ??bKz￥÷E ^|1?1? ??I ??Bb1 L?é??o T my1
Yè P¨?]t?V U μ?]+ ?￥?
[úù?Y? -W￥M ??bt?￥ê4 Es×1
?T P¨??
 A ?? ?°4
ü? P12T?Btμ¨￥?é >bMQ
?Tê4¤?
ü?V? 12 T?á ?s?t×1￥2 T???ê?b è?
?T¨?t?V UBFú o￥ ?
5?? ￥Bê?? 3lM H
5??t??]
ü V[? ysbt?￥ê4 V[? ?4???z
?Kz?è?ZEBáb¨ ?y???￥? H? ??F q???s0m?èq ?¨￥t?s ?ZE
1??^1vE¤ s
V 7.3
b V 5.3 ? ?sFZE?}V?t? ?? ? ?+? t? Asp (D), Glu (E) ?? ￡? His (H), Arg (R), Lys (K) a? §? Ser (S), Thr (T), Asn (N), Gln (Q) ? s? Ala (A), Val (V), Leu (L), Ile (I), Met (M)  ￡?
{| y a? Phe (F), Tyr (Y), Trp (W)  ￡?
{&ì ,? Pro (P), Gly (G) § y2+ y 5? Cys (C) ???= ;o ?? * V??¨￥sFZE?¨ ?us?]FY￥t?D?q???m?èq ? ?¨ZEBá ? 1??￥ 6B?×1¨o ^? 9? W￥1"
i?Nw ? ìé? ?￥T?1"b V[YV9 ????￥￥? ?"9 ????￥??M ??￥ ?"¤ ???? 1"b?BZE"  V[v { 3? W￥T?1"?
9 V¨ ??1é b ?T? ￥M ??′??? ′
* 1μ V? ^? WT?1"?ù
9 V? ^1?μp -)b Cμ￥èq¨￥'  ^ V¨ ?S?￥3 g? ?
?? I ê?3 g?b ?"￥èq|? Ec?W%o b ? 7.9??
á ì|? A?
*téM_OM ????ú￥? 
?¨1?1 ZE|?¤?M? ?i￥2T
7?? éMμ?v7M ????? H
?¨1?ZE ¤￥2T5?? ?XbN H
 my? I ü¤A¤ Esμ¨bYV my??
 V P2 TM¤¤í L=bN?
?¨??]￥ZEé?s
|2T8?
 ^B??-μr￥ ZEb1÷z1 ?3? 1￥e ???5
??D V?D? my1￥ZE
iü1 2TD9 ?1?1¤?￥2TF[1?b 5.7 ]?E ]?E Lé ^üó?￥ ?μ? ] Hé?1
7? ^  1sFé?1b ' ±X ^|B?=?￥? ??? ?
n? 6c
 ?Z????b ?￥? ?Q?  ?D1￥?  ?b? ?ZE?9 ?￥"d'÷1p?ú
Yè ^é?  ￥?￥? ￥1b 5.8 ?éE ? ?ZE?Kè¨￥ü ^ Clustal
 ? ^? Feng? Doolittle? 1987M4￥
Feng ? Doolittle
 1987
 b??? L=￥ ?  ?¨?￥? ? ?? ? ?é?? ￥1? tC L
yNv ? L¨￥? 1???¨? T ?E
[?? ?ˉbClustal ￥ ' ±X ^?M ?? Yè μé?M1??BL !b1V??
5 ?μ￥? é?  1i9 ? ? ì￥M ??s ?′
?a? M ??s ?′| ? ìs???F
i ?F- Wé?1
9 ?M ??s ?′b? M ??s ?′??sF1
°?¤?K?12Tb 1V??
M ????ú￥? 5é?1
7  ??ù￥? @Fa ?bT1?? ￥B?s
Clusal V[ {¨?yé? ?￥ ? b Clustal??μ??'
 ClustalW
Thompson?
 1994

? T?1"?í￥?  W bêf ?
????T?1"?ù￥? -W?? bêb]"
M ???ú￥? 1 2T?￥?lM?
 V¨??M?+ yê? bê@s′￥vl
w??ê?￥? M s?b Clustal ^ ?nèq
??^Vo ó? /
? ?èqB
<W¨?? sb Clustal ?|?￥ ? ì T ? EMBL/SWISSPROTaNBRF/PIRaPearson/FastAaGCG/MSF
 [# Clustal ' &?l￥ì Tb ?￥ {ì T V[ ^ Clustal ì T
9 V[ ^ V¨? GDEa PhylipaGCG?èq￥ì Tb m 7.1  / F í??a} ? s8
G-protein copupled receptors
e? GPCRs
? 1?s2Tb1?¨? 8? ?
 {ì T?¨ GCG/MSFì Tb?t?  μú￥ M ??7OéM_
2T Es ?Xbm? V[ üA1 Aμ ? bê??u×
B? ^ ?? ? A2AA s8M ?? μ GPQ? GQQ???￥??/?
m? ?s·§

6B? ^? ? A2AB s8?￥?????/?
m?/?·§
b 5.9? 1￥ ?  o ? 1￥il? ??ü?]? ?￥M1? ￥12T?v+?￥ì T { 
iOB?? Q? ? ì-W￥M ??b? 12T ?4￥??4ú ?  o ? ì 2 ù9 μ?vúùbyN
ZL L¨￥? 1 ?  o9ü?7 3b "-
o ó?  V¨￥? 1 ?  oXü? b?Bt ?¨9 ???|B Q ?  o?EBs ?
6?Bt5 ^YV my1?ZE? yEBy=Q ?  ob 1??Z ?￥=?? ' ?S?
4[BBW ?b?7
????t? 1 ?  oy￥ZE? ? ì￥??μ ? 3b
[  è0lV ü
Pfam ??¨?} ?E7?ü|y_°￥1?1??á 3￥2T V??á4[? ￥p2Tby1 ?Q?} ?á 3￥L?2T
? ?"?}Q ?￥9F 7 ?F ?
?áC ?￥p1
K??á4[us? ??á 3￥?￥?T? 1"?ù￥? -W?￥￥uYb 8  ? ?
Tbò??]1ZE? ?¤2T-W￥uY
A? Es×1b1?m 7.1 ? 7.2￥2T V[¤?
? μ?úM ??￥BF? -W￥1
1?1ZE ^?μ r￥bB?? ￥T?1"M¤?ù
 ?¤2Tü?* 1 V?b7YVm 7.2? 7.3￥1?
 á ì V[ A
?1¤?1? V L7? μ ü? 3tDil￥12T
1?μr￥ZE ^ 12Té? myI ???b??y=Q ?  o ^dè×1￥?bê4Cμ￥ ?  T? 8 7 ?  oy1-￥ ?  o"d H
?tCμ ?  o￥ V L?A? ?|è 0￥ ?b 5.10 ?? 1￥ ?  o ? ì ? 6 c￥Ka?s
á ì)  ?¨ ?? 1é? ?  o ? ì￥ò?ZEb]"
 ? 19 V[¨? ?  o ? ìb??- ?o ￥
?? 1￥2T V[w¨? í ?yEB￥+?￥?  T
??5Vr Ta? ?
?  va? ·?m?[#? ? f??bμ1?aé?  T=Q ?  o￥ ? ì?sZE
|? 8c?W%o b D? ?? 1￥ ?  oZEM1
?? 1￥ ?  o ? ì??? ÷￥ ?
 P ? ì2T÷F 2 ù
?.1÷úb ?￥?? ^ ??n￥ HW÷é
iOK?2Tü è÷F??^sb B? a ?
_?? Yè5é?? ?? 1￥ ?  o ? ìb? ? ì2T¤?X ?yEB￥t?
 àμóM ????ú￥"S? 
5 V? k?? 1 ￥ ?  o ? ìZ?
"￥?s*tM ?????7?μ 3tDil￥"S? b 5.10.1 ê?+s? BLAST?} ? ì ê?+s? BLAST
Position-Specific Iterated BLAST
e? PSI-BLAST
?} ? ì
Altschul ?
1997

 ^B?| ?? 1?? 12?B￥ ?  o ? ìZEb D5[/ Y LXü'¤?a]
??  T￥ ?  o ? ì 2 ù?úa+s??z
y 7 V[?CBt  ??ù?? μ 3tDil￥M ?? 
?￥?@-)9??í[- jb " 31v ￥9 ?'÷?B???
? ? ì2T￥s3 dèèM? ?4b?t??y íK?  ?￥ L= P¨S?bPSI-BLAST ￥' ± ^?? K￥ ? ì2T
Gv?5 ?l￥M ???′|? s??]￥F
yB?ê?+s?￥? ?
iYVQ?}? ?é?B? ?[4ú ? ì￥ 2 ùb ? ??} ?EB"
 PSI-BLASZE;μ? é)
9μ ?￥@hb è?
?T1 -?ü?e?aa]÷ 8??ˉ￥×ˉ? à7?
1??} ? ìV??y1? t×ˉ? ￥??7 >?
Holm
 1998
bL??B }￥ ? ì2TCB?p? 
* 1 K? ? ì2T?|?C??ù?￥í1? 
n 7.9 ?
byN
1 D ?"v ￥ p?￥
-%s ? ì2Tó￥]÷1"M¤dè×1b ? Bc??tc?
á ìo  μ1 ?? ?? 1￥ZE
9· ??^? 1?1ZE7 V?á 3￥pb/Bc|W%o ?? ?¨? 1￥á 3￥? ? í ?yEB￥+?
i??) myZE?1?ZE￥a ?b 5.11 'cl2 ? ? B?yEB?F? ￥s31úb?yEB?]??-W￥1"b ? s V¨ ?￡ UyEB￥ o?b ? ? D ?? 1B"
? 1???b12T àμ '?? ' p-s
7o? a1? ^? V[1??1Q?  3t ? ￥+?b ? ? ?? ??2￥? 1?????
y1 ??????Q? ?μaQ￥ 3tD?b? ?ZEò1μB?￥?¨S?
 ??d￡? 20b ? ? ? 1 V[ ATBf=?V
V? ?B?}VB?? 
 ?B }VB ??￥ê?b1-?? ?￥ê?1 'ê?
 71a?? ?￥ ê??Mê?b ? ? ? 1 ?31￥ HW ?? ? ?9F7· ?9éb? ? 1?? ?¨? T ?E[??9 ?ˉ?
i¤?idKa???z￥2Tb ? ? m?1üè$a1{μ?4?
?9 ?1?12T+??31 my? ?b? I ?? ^A? V ￥y b ? ?  ?μ? ] Hé?1￥9 ? v
yNo?¨??é￥? ? b ? ? ?é T? 1ZE? T÷ ?￥s|?   1bM ???ú￥ 51
M ????￥aF?bYVs V?￥é?1"
??ZE V[) ?B ??￥ ?  b ? ? Vo ó?  V P¨￥ ?  o?
?μt?9 ???1?á 3
μ￥ üV|y) ?b ? ? P¨???1?1á 3￥ ?  o H??i
+Y ^?? ￥M ???? ?￥f ?/÷3è 0
y1?t12T?μv ￥ bê??
 .à V?￥b ? ? ?? 1￥ ?  o ? ì???? 7?b PSI-BLAST ^| ?? 1 ?? 12?B￥?} T ?  o ? ì??bD5 ?￥? ?? y
? ?μ?}' &%μ￥??
μ H?¤??z￥2Tb 5.12 éB?·2 Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ., Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997 Sep 1;25(17):3389-402. Holm L., Unification of protein families. Curr Opin Struct Biol. 1998 Jun;8(3):372-9. Feng DF, Doolittle RF., Progressive sequence alignment as a prerequisite to correct phylogenetic trees. J Mol Evol. 1987;25(4):351-60. Feng DF, Doolittle RF., Progressive alignment of amino acid sequences and construction of phylogenetic trees from them. Methods Enzymol. 1996;266:368-82. Thompson JD, Higgins DG, Gibson TJ., CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994 Nov 11;22(22):4673-80.