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Phylogeny of Cationic Receptor Subunits  May 22th 2001

Methods

The alignments were constructed using the program CLUSTALW:

THOMPSON et al. (1994). CLUSTALW: improving the sensitivity of progressive multiple sequence alignments through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22: 4673-4680

The "hypervariable" portions, of variable lengths in different subunits, were removed, in order to avoid bias, particularly with distance-methods. The phylogenetic inferences were computed using the package PHYLIP:

FELSENSTEIN, J (1993). PHYLIP, phylogenetic inference package. Distributed by the author, department of Genetics, University of Washington, Seattle.

according to the methods presented in:

Nicolas Le Novère and Jean-Pierre Changeux (1995). Molecular evolution of the nicotinic acetylcholine receptor: an example of multigene family in excitable cells. J Mol Evol 40: 155-172.
(HTML version, Postscript version)

Above the branches are the bootstrap scores (each alignment is bootstrapped 1000 times) of the Maximum Parsimony (rounded to the nearest integer). Under the branches are the bootstrap scores of the Neighbor-Joining. The triplications denote uncertainties, i.e. total opposition of the methods, or the two methods providing bootstrap scores below 50 %. When the topology obtained contradicts the species systematic, the trees are corrected, the new branches being annotated "syst".

The position of subunits linked by dotted line have been determined with an independant alignment (because the sequence is very short and could distort the general result).

Those trees were experimentally designed. They do not fully represent the personal opinion of the author, and they are surely not fully identical to the actual evolutionary history of the subunits.


Contents

General View

Click on the denomination of a subset to get a more detailed tree.

Alignment

16 sequences, 364 positions. Outgroup is human GABAA α1.

Results

                   648|==== ACHa3hosa
                 |====|              
                 | 842|==== ACHa1hosa
                 |                   
                 |========= ACHdhosa 
              444|                   
            |====|========= ACHb2hosa
            | 953|                   
         525|    |========= ACHb1hevi
       |====|    |                   
    913| 887|    |========= ACHa1mype
  |====|    |                        
  | 967|    |============== ACHa7hosa
  |    |                             
  |    |          1000|==== ACHa10hosa
  |    |==============|               
  |               1000|==== ACHa9hosa 
  |     
  |                447|==== ACHdeg3cael  
  |===================|                  
  |                737|==== ACHacr17cael 
  |               
  |                998|==== 5HT3Ahosa    
  |===================|                  
  |                973|==== 5HT3Bhosa    
  |
  |               1000|==== ACHt01h10_1cael
  |===================|                    
                  1000|==== ACHt01h10_2cael
\
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| 
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| Acetylcholine Activated Subfamilies
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/

\
| DEG3 Subfamily
/

\
| 5-HT Subfamily
/

\
| T01H10 Subfamily
/

Acetylcholine Activated Subfamilies

Alignment

14 sequences, 439 positions. Outgroup = human 5-HT3A.

Results

                        437|==== ACHa1hosa
                      |====|              
                   414| 781|==== ACHa3hosa
            |=========|                   
            |      817|========= ACHb3hosa
            |                             
            |      662|========= ACHb2hosa
            |    |====|                   
            | 541| 916| 687|==== ACHb1hosa
            |====|    |====|              
         770| 639|      840|==== ACHdhosa 
       |====|    |                        
       | 964|    |============== ACHb1hevi
       |    |                             
    785|    |           916|==== ACHa1mype
  |====|    |==============|              
  | 835|                986|==== ACHunc38cael
  |    |                                     
  |    |                984|==== ACHa7hosa   
  |    |===================|                 
  |                     993|==== ACHa7_1hevi 
  |                                 
  |                    1000|==== ACHa9hosa  
  |========================|                
                       1000|==== ACHa10hosa 
\
| 
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| The Nicotine Activated Subfamilies
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\
| α9 Subfamily
/

Nicotine Activated Subfamilies

Alignment

16 sequences, 434 positions. Outgroup = human α9

Results

            |============== ACHa1hosa   
         549|                           
       |====| 408|========= ACHa3hosa   
       | 866|====|                      
       |      549| 588|==== ACHa2hosa   
       |         |====|                 
       |           779|==== ACHb3hosa   
       |                                
       |           957|==== ACHdhosa    
       |         |====|                 
    829|      883|1000|==== ACHghosa    
  |====|    |====|                      
  | 994| 836| 993|========= ACHb1hosa   
  |    |====|                           
  |    | 998|============== ACHb2hosa   
  |    |                                
  |    |=================== ACHb1hevi   
  |    |                                
  |    |      854|========= ACHunc38cael
  |    |=========|                      
  |           995|    |==== ACHa1mype   
  |              | 687|                 
  |              |====|==== ACHa3mype   
  |                939|                 
  |                   |==== ACHa2mype   
  |
  |                997|==== ACHa7hosa   
  |===================|                 
                  1000|==== ACHa7drme   
\
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| The Heteromeric Receptor Subfamilies
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/

\
| α7 Subfamily
/

Heteromeric Receptor Subfamilies

Alignment

25 sequences, 426 positions. Outgroup = human α7

Results

                            1000|==== ACHa3hosa
                           |====|              
                        711|1000|==== ACHa6hosa
                      |====|                   
                      | 697|1000|==== ACHa2hosa
                      |    |====|              
                   328|     1000|==== ACHa4hosa
                 |====|                        
                 | 798|     1000|==== ACHb3hosa
              526|    |=========|              
            |====|          1000|==== ACHa5hosa
            | 948|                                
            |    |          1000|==== ACHa1bota
            |    |==============|              
            |               1000|==== ACHa1hosa
         225|
       |====|               1000|==== ACHb2hosa
       | 690|    |==============|              
       |    |    |          1000|==== ACHb4hosa
       |    | 346|
       |    |====|    |============== ACHb1hosa
       |      973| 952|                        
    344|         |====|    |========= ACHdhosa 
  |====|          1000| 999|                   
  | 687|              |====| 939|==== ACHghosa 
  |    |               1000|====|              
  |    |                     991|==== ACHehosa 
  |    |
  |    |                    1000|==== ACHacr2cael
  |    |========================|                
  |                         1000|==== ACHb1hevi  
  |
  |                          384|==== ACHa1mype 
  |                        |====|               
  |                     349| 719|==== ACHa2mype 
  |                   |====|                    
  |                526| 510|========= ACHa4mype 
  |              |====|                         
  |              | 924|      946|==== ACHa4drme 
  |           403|    |=========|               
  |         |====|           999|==== ACHa3mype 
  |         | 767|                              
  |      487|    |           360|==== ACHunc38cael
  |=========|    |==============|                 
         711|                791|==== ACHunc63cael
            |                                     
            |======================== ACHacr8cael 
\
|
| 
|
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| α2-6,β3 Tribe
|
|
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/

\
| α1 Tribe
/ 

\
| β2,4 Tribe            
/ 

\
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| β1, γ, δ, ε Subfamily
| 
|
|
/

\
| ARD Subfamily
/

\
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| ALS Subfamily
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/

Comments

  • The two groups muscle non-α with β2,4 and α1 with α2-6/β3 are not highly supported. The evolution rates of β2,4 common ancestor on one part, and of α1 subunits on another part, are far lower than those of the other subunits (this is visible in the unability to cleanly eliminate the triplications between α1 orthologs, see below). This implies that we cannot really trust the trees reconstructed from sequences to locate the split of those subunits. Moreover, the genic structure of β2 and β4 subunits is exactly identical to the genic structure of α2-6/β3 and very different to the muscle non-α genic structure. It is in favor of a clade with all the heteromeric neuronal receptor subunits. See Le Novère and Changeux 1995 for details. The topology would therefore be:

              |==== a2-a6,b3 
         |====|
         |    |==== b2,4
    |====|    
    |    |    |==== a1
    |    |====|
    |         |==== b1,g,d,e
    |
    |============== Drosophila
    |
    |============== Drosophila
    

    Some analysis could also suggest something like:

              |==== a2-a6,b3 
         |====|
         |    |==== b2,4
    |====|
    |    |========= ALS subfamily
    |    
    |         |==== a1
    |    |====|
    |====|    |==== b1,g,d,e
         |
         |========= ARD subfamily
    

    If you do not know how to spend your next vacation, please sequence the genomes of lophophorates and of vertebrate cousin such as Amphoxius (Branchiostoma lanceolatum)!

  • The branching of acr8cael is wrong. It should cluster with the other nematod subunits of the ALS subfamily.

α2-6,β3 Tribe

Alignment

27 sequences, 424 positions. Outgroup = human α7.

Results

                            1000|==== ACHa6mumu
                           |====|
                        960|1000|==== ACHa6rano
                      |====|
                  1000| 958|========= ACHa6hosa
                 |====|
              711|1000|============== ACHa6gaga
            |====|
            | 610|=================== ACHa3caau
            |
         999|                535|==== ACHa3hosa
       |====|              |====|
       |1000|           974| 735|==== ACHa3bota
       |    |      999|====|
       |    |=========| 991|========= ACHa3rara
       |          1000|
       |              |============== ACHa3gaga
    996|
  |====|                   |========= ACHa2hosa
  | 933|                996|
  |    |              |====|1000|==== ACHa2rano
  |    |           932|1000|====|
  |    |         |====|         |==== ACHa2mumu
  |    |         | 950|
  |    |         |    |============== ACHa2gaga
  |    |         |
  |    |     1000|           912|==== ACHa4mumu
  |    |=========|         |====|
  |          1000|      983| 991|==== ACHa4rano
  |              |    |====|
  |              |1000|1000|========= ACHa4hosa
  |              |====|
  |                950|============== ACHa4gaga
  |
  |                        |========= ACHb3hosa
  |                     870|  
  |                   |====| 999|==== ACHb3rano
  |                862|syst|====|
  |              |====|     1000|==== ACHb3mumu
  |              |1000|
  |           999|    |============== ACHb3gaga
  |         |====|
  |         |1000|           685|==== ACHb3acaau
  |         |    |==============|
  |      999|                942|==== ACHb3bcaau
  |=========|
        1000|               1000|==== ACHa5mumu
            |              |====|
            |           995| 990|==== ACHa5rano
            |     1000|====|
            |=========| 992|========= ACHa5hosa
                  1000|
                      |============== ACHa5gaga

Comments

The subunits α3 and α6 are among the closest. It could well be that "α3" of goldfish (Carassius auratus) is in fact α6.

β1, δ, γ, ε Subfamily

Alignment

25 sequences, 395 positions. Outgroup = human α4 and human α5.

Results

                             945|==== ACHb1rara
                           |====|     
                       1000| 998|==== ACHb1mumu
                      |====|
                      |1000| 549|==== ACHb1hosa
                   762|    |====|     
                 |====|      884|==== ACHb1bota
              999| 950|
  |==============|    |============== ACHb1xela
  |          1000|
  |              |=================== ACHb1toca
  |
  |                         1000|==== ACHdrara
  |                        |====|     
  |                    1000|1000|==== ACHdmumu
  |                   |====|
  |                   |1000| 480|==== ACHdhosa
  |                556|    |====|     
  |              |====|      925|==== ACHdbota
  |           888| 591|
  |         |====|    |============== ACHdgaga
  |      998| 959|
  |    |====|    |=================== ACHdxela
  |    |1000|
  |    |    |======================== ACHdtoca
  |    |
  |    |                     951|==== ACHgrara
  |    |                   |====|     
  |    |               1000|1000|==== ACHgmumu
  |    |              |====|
  | 982|              |1000| 596|==== ACHghosa
  |====|              |    |====|     
   1000|          syst|      844|==== ACHgbota
       |      995|====|
       |    |====|    |============== ACHggaga
       |    |1000|    
       |    |    |=================== ACHgxela
       |    |
       |    |                959|==== ACHerara
       | 994|              |====|     
       |====|          1000|1000|==== ACHemumu
        1000|         |====|
            |         |1000| 840|==== ACHehosa
            |     syst|    |====|     
            |    |====|      880|==== ACHebota
            | 535|    |
            |====|    |============== ACHexela
              925|    
                 |=================== ACHgtoca

Comments

The loosely supported grouping of Torpedo γ and Xenopus ε means probably that the duplication ε/γ is about concomitant of the divergence between chondrichthies and osteichthies.

β2,4 Tribe

Alignment

10 sequences, 442 positions. Outgroup = human α4.

Results

                   977|==== ACHb2rara
                 |====|
              997| 983|==== ACHb2mumu
            |====|
         995|1000|========= ACHb2hosa
  |=========|
  |     1000|============== ACHb2gaga
  |
  |======================== ACHb2caau
  |
  |           468|========= ACHb4hosa
  |         |====|
  |         |syst|1000|==== ACHb4rano
  |     1000|    |====|
  | 969|====|     1000|==== ACHb4mumu
  |====|1000|
   1000|    |============== ACHb4bota
       |
       |=================== ACHb4gaga

Comments

The subunits β2 and β4 are very close. It is not clear at all that "β2" of goldfish (Carassius auratus) is not in fact β4.

α1 Tribe

Alignment

10 sequences, 456 positions. Outgroup = human α4.

Results

                        406|==== ACHa1bota
                      |====|
                   566| 765|==== ACHa1cafa
                 |====|
             1000| 885|========= ACHa1hosa
            |====|
            |1000|     1000|==== ACHa1rara
        syst|    |=========|
       |====|          1000|==== ACHa1mumu
       |    |
   syst|    |           962|==== ACHa1axela
  |====|    |==============|
  |    |                931|==== ACHa1bxela
  |    |
  |    |======================== ACHa1dare
  |
  |                    1000|==== ACHa1toca
  |========================|
                       1000|==== ACHa1toma

ALS Subfamily

Alignment

25 sequences, 420 positions. Outgroup = human α4.

Results

                                  :.. ACHtar1trco
                                  :
                            1000|==== ACHahaco
                 |==============|
                 |         :1000|==== ACHunc38cael
                 |         :    :
                 |         :    :.... ACHaassu
                 |         :
              302|         :......... ACHronvo
            |====|
            | 699|           965|==== ACHacr8cael
            |    |         |====|
            |    |     1000| 998|==== ACHacr13cael
         423|    | 755|====|
  |=========|    |====|1000|========= ACHacr12cael
  |      736|      796|
  |         |         |============== ACHzk973_5cael
  |         |
  |         |======================== ACHunc63cael
  |
  |                        |========= ACHa2lomi
  |                        |
  |                     995|========= ACHa4mype
  |         |==============|
  |         |          1000| 985|==== ACHsbddrme
  |         |              |====|
  |      750|                998|==== ACHa3hevi
  |    |====|
  |    | 652|    |=================== ACHa4drme
  |    |    |    |              :
  |    |    |    |              :.... ACHa1lomi
  |    |    |    |              :
  |    |    |    |              :.... ACHa5mype
  |    |    | 979|        
  |    |    |====|          1000|==== ACHa3mype
  |    |     1000|    |=========|
  |    |         |    |     1000|==== ACHa2apgo
  |    |         |====|
  |    |              | 985|========= ACHa3drme
  |    |              |====|
  |    |               1000| 802|==== ACHa1hevi
  |    |                   |====|
  |====|                    1000|==== ACHalsmase
       |
       |                     921|==== ACHa3lomi
       |                   |====|
       |               1000| 992|==== ACHalsdrme
       |===================|
       |               1000|========= ACHa2mype
       |
       |                   |========= ACHal1scgr
       |                882|
       |              |====| 975|==== ACHsaddrme
       |          1000| 973|====|
       |==============|      999|==== ACHa2hevi
                  1000| 
                      |============== ACHa1mype
   

Comments

  • The position of tar1trco, αassu, ronvo, α1lomi and α5mype have been determined by another, shorter, alignment.

  • There are five tribes of arthropod subunits. Authors, it would be a good idea to homogeneize the terminology:

    α1 alsdrme, α2mype, α3lomi
    α2 saddrme, α1mype, α2hevi, αL1scgr
    α3 α3drme, α1hevi, α2apgo, α3mype, alsmase
    α4 α4drme, α1lomi, α5mype,
    α5 sbddrme, α3hevi α4mype, α3lomi

  • The subunits of nematods and of arthropods form two monophyletic groups. The common ancestor of nematods and arthropods therefore posseded only one ALS gene, the diversification occuring independantly after the separation of lineages.

ARD Subfamily

Alignment

10 sequences, 445 positions. Outgroup = human α4.

Results

            |========= ACHarddrme
            |
        1000|========= ACHblomi
  |=========|
  |     1000| 892|==== ACHb1hevi
  |         |====|
  |          1000|==== ACHb1mase
  |
  |           995|==== ACHlev1cael
  |         |====|
  |         |1000|==== ACHunc29cael
  |      993|
  |    |====|========= ACHacr3cael
  | 437|1000|
  |====|    |========= ACHacr2cael
    603|
       |============== ACHnaapca

Comments

The subunits of nematods and of arthropods form two monophyletic groups. The common ancestor of nematods and arthropods therefore posseded only one ARD gene, the diversification occuring independantly after the separation of lineages.

α7 Subfamily

Alignment

19 sequences, 422 positions. Outgroup = human α4

Results

                        853|==== ACHa7hosa
                      |====|
                   946| 554|==== ACHa7bota
                 |====|
                 | 980|1000|==== ACHa7mumu
             1000|    |====|
            |====|     1000|==== ACHa7rano
        1000|1000|
  |=========|    |============== ACHa7gaga
  |     1000|
  |         |=================== ACHa8gaga
  |
  |              |============== ACHacr11cael
  |              |
  |              |      837|==== ACHacr9cael
  |              |=========|   
  |           976|      996|==== ACHacr14cael
  |         |====|
  |         | 995| 920|========= ACHacr7cael
  |         |    |====|    :
  |         |    | 997|    :.... ACHacr10cael
  |      591|    |    |
  |    |====|    |    |========= ACHacr15cael
  | 578| 391|    |
  |====|    |    |============== ACHacr16cael
    492|    |
       |    |=================== ACHacr19cael
       |
       |               1000|==== ACHa7_2hevi
       |           986|====|
       |==============|1000|==== ACHa6drme
                  1000|
                      |1000|==== ACHa7_1hevi
                      |====| 
                       1000|==== ACHa7drme

Comments

  • The position of ACHacr10 has been determined from another alignment.

  • The subunits of nematods, arthropods and vertebrates form three monophyletic groups. The common acoelomate ancestor therefore posseded only one α7 like gene, the diversification occuring independantly after the separation of the three lineages.

α9 Subfamily

Alignment

5 sequences, 412 positions. Outgroup = human α7.

Results

        1000|==== ACHa9hosa
       |====|
   1000|1000|==== ACHa9rara
  |====|
  |1000|========= ACHa9gaga
  |
  |syst|========= ACHa10gaga
  |====| 
       |1000|==== ACHa10rano
       |====|
        1000|==== ACHa10hosa

DEG3 Subfamily

Alignment

8 sequences, 318 positions. Outgroup = human α7.

Results

             1000|==== ACHacr17cael
  |==============|
  |          1000|==== ACHacr18cael
  |
  |           998|==== ACHacr20cael
  |         |====|
  |      995|1000|==== ACHacr23cael
  |    |====|
  | 998|1000|========= ACHacr4cael
  |====|
   1000|         |==== ACHdeg3cael
       |      881|
       |=========|==== ACHy73f8a_30cael
              984|
                 |==== ACHacr5cael

5-HT3 Subfamily

Alignment

5 sequences, 445 positions. Outgroup = human α7.

Results

        1000|==== 5HT3Amumu
       |====|
   1000| 982|==== 5HT3Arara
  |====| 
  |1000| 814|==== 5HT3Acapo
  |    |====|
  |      909|==== 5HT3Ahosa
  |
  |============== 5HT3Bhosa

T01H10 Subfamily

Alignment

6 sequences, 256 positions. Outgroup = Cænorabditis acr22.

Results

             1000|==== ACHt01h10_6cael
            |====|
         250|1000|==== ACHt01h10_5cael
       |====|
    371| 648|========= ACHt01h10_1cael
  |====|
  | 528|============== ACHt01h10_7cael
  |
  |           813|==== ACHt01h10_3cael
  |==============|
              726|==== ACHt01h10_2cael

Related Bibliography

Le Novère N., Changeux J.-P. (1995). Molecular evolution of the nicotinic acetylcholine receptor: an example of multigene family in excitable cells. J Mol Evol 40 : 155-172.

Mongan N.P., Baylis H.A., Adcock C., Smith G.R., Sansom M.S.P., Sattelle D.B. (1998). An extensive and diverse gene family of nicotinic acetylcholine receptor alpha subunits in Cænorhabditis elegans. Recept Channels, 6: 213-228.

Ortells, M. O. and Lunt, G. G. (1995). Evolutionary history of the ligand-gated ion-channel superfamily of receptors. Trends Neurosci, 18(3): 121-126.

Last modification: Wed Nov 24 10:59:05 GMT 2004 | Nicolas Le Novère

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