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Phylogeny of Anionic Receptor Subunits  October 13rd 2000

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

28 sequences, 303 positions. Outgroups are human ACHα7 and α9.

Results

                            1000|==== GABr3rano
                      |=========|
                      |     1000|==== GABr1hosa
                   668|
            |=========|      863|==== GABphosa
            |      808|    |====|
            |         | 461| 965|==== GABdhosa
            |         |====|
            |           776| 811|==== GABb1hosa
            |              |====|
         618|                985|==== GABbdrme
       |====|
       | 409|                831|==== GABrdldrme
       |    |===================|
       |    |                867|==== GABunc49bcael
       |    |
       |    |                938|==== GABgrddrme
       |    |===================|
       |                     990|==== GABa1hosa
       |
       |                     801|==== GLYa1hosa
       |========================|
    513|                     999|==== GLYbhosa
  |====|
  | 545|                954|========= GLUclacael
  |    |===================|
  |    |                999|========= GLUclbcael
  |    |
  |    |============================= GABzlyst
  |    |
  |    |                   |========= GABc39b10_2cael
  |    |                673|
  |    |===================| 938|==== GABt24d8_1cael
  |                     982|====|
  |                          999|==== GABc09g5_1cael
  |
  |                          887|==== GABf09c12cael
  |=============================|
                             998|==== GABc53d6_3cael
\
|
|
|
|
| beta - delta - pi - rho
|
|
|
|
/

\
| RDL-like subunits
/

\
| alpha - gamma
/

\
| glycine receptor subunits
/

\
| anionic glutamate receptor subunits
/









\
| new subfamily (only in C elegans)
/

β, δ, π, ρ Subunits

Alignment

25 sequences, 425 positions. Outgroups are Lymnea "GABA" ζ and human glycine α1 subunits.

Results

Upper-level

                             777|==== GABb1mumu
                           |====|
                           | 982|==== GABb1rasp
                       1000|
                      |====|syst|==== GABb1hosa
                      |    |====|
                   677|         |==== GABb1bota
                 |====|
                 | 844|     1000|==== GABb2hosa
              685|    |=========|
            |====|          1000|==== GABb2rasp
            | 930|
            |    |          syst|==== GABb3hosa
        1000|    |      935|====|
       |====|    |=========|    |==== GABb3rasp
       |1000|           998|
       |    |              |========= GABb3gaga
    965|    |
  |====|    |======================== GABb4gaga
  | 998|
  |    |                     999|==== GABbdrme
  |    |========================|
  |                         1000|==== GABblyst
  |
  |                         1000|==== GABdrara
  |                        |====|
  |                     436|1000|==== GABdhosa
  |========================|
  |                     908|========= GABphosa
  |
  |                         1000|==== GABr1rano
  |                        |====|
  |                     837|1000|==== GABr1hosa
  |                   |====|
  |                   | 871|========= GABr1bmoam
  |                995|
  |              |====|      859|==== GABr2amoam
  |              |1000|    |====|
  |              |    | 999| 510|==== GABr2bmoam
  |          1000|    |====|
  |==============|      996|1000|==== GABr2hosa
             1000|         |====|
                 |          1000|==== GABr2rara
                 |
                 |=================== GABr3rano
\
|
|
| beta1
|
|
/

\
| beta2
/

\
|
| beta3
|
/

  beta4

\
| beta deuterostomata
/

\
| delta
/

  pi

\
|
| rho1
|
/

\
|
|
| rho2
|
|
/

  rho3

RDL-like Subunits

Alignment

8 sequences, 335 positions. Outgroups are Human GABA β1 and Human GABA α1.

Results

Upper-level

                   948|==== GABrdlaeae
                 |====|
              628| 983|==== GABrdldrme
            |====|
        1000| 875|========= GABrdlceca
       |====|
    921|1000|============== GABa3hevi
  |====|
  | 972|=================== GABf11h8_2cael
  |
  |======================== GABunc49bcael

α, γ Subunits

Alignment

37 sequences, 348 positions. Outgroups are Human GABA β1 and Drosophila RDL subunits.

Results

Upper-level

                                      syst|==== GABa1mumu
                                     |====|
                                     |    |==== GABa1rara
                                |====|
                                |    |syst|==== GABa1bota
                            1000|    |====|
                           |====|         |==== GABa1hosa
                           |1000|
                           |    |============== GABa1gaga
                        689|
                      |====|           766|==== GABa2bota
                      | 934|         |====|
                      |    |     1000| 832|==== GABa2hosa
                      |    |=========|
                   408|          1000|syst|==== GABa2mumu
                 |====|              |====|
                 | 560|                   |==== GABa2rara
                 |    |
                 |    |               1000|==== GABa5rara
                 |    |===================|
             1000|                    1000|==== GABa5hosa
            |====|
            |1000|                     497|==== GABa3mumu
            |    |                   |====|
            |    |               1000| 663|==== GABa3rara
            |    |===================|
            |                    1000|syst|==== GABa3hosa
        1000|                        |====|
       |====|                             |==== GABa3bota
       |1000|
       |    |                          380|==== GABa4hosa
       |    |                        |====|
       |    |                    1000| 665|==== GABa4bota
       |    |              |=========|
       |    |              |     1000|========= GABa4rara
       |    |           963|
       |    |==============|           871|==== GABa6mumu
       |               1000|         |====|
       |                   |     1000| 993|==== GABa6rara
       |                   | 540|====|
       |                   |====|1000|========= GABa6hosa
       |                     773|
    986|                        |============== GABa6caau
  |====|
  |1000|                              1000|==== GABg1gaga
  |    |                   |==============|
  |    |                   |          1000|==== GABg1rano
  |    |                   |
  |    |                   |          syst|==== GABg2rara
  |    |                745|         |====|
  |    |              |====|      972|    |==== GABg2mumu
  |    |              | 936|    |====|
  |    |              |    |    | 976|syst|==== GABg2hosa
  |    |              |    | 999|    |====|
  |    |              |    |====|         |==== GABg2bota
  |    |           530|     1000|
  |    |         |====|         |============== GABg2gaga
  |    |         | 992|
  |    |         |    |               1000|==== GABg3mumu
  |    |      981|    |              |====|
  |    |=========|    |           361|1000|==== GABg3rano
  |          1000|    |==============|
  |              |                966|========= GABg4gaga
  |              |
  |              |============================= GABehosa
  |
  |                                    871|==== GABhg1haco
  |=======================================|
                                       966|==== GABgrddrme
\
|
|
|
| alpha1
|
|
|
/

\
|
|
| alpha2
|
|
/

\
| alpha5
/

\
|
|
| alpha3
|
|
/

\
|
| alpha4
|
/

\
|
|
| alpha6
|
|
/

\
| gamma1
/

\
|
|
|
| gamma2
|
|
|
/

\
| gamma3
/

  gamma4

  epsilon

Comments

  • There is a possibility that chick γ4 would in fact the avian ortholog of γ3.

  • Human ε is clearly homologous to the γ subunits. It is also clear that it is not a known paralog. Since it is supposed to fill the same role than within the oligomer, there is no point to give it a different name. A more reasonable name would therefore be γ5 (providing that chick γ4 is not in fact γ3).

Glycine Receptor Subunits

Alignment

15 sequences, 336 positions. Outgroups are human GABA β1 and human GABA α1.

Results

Upper-level

                      |========= GLYbhosa
                  1000|
  |===================|syst|==== GLYbrano
  |                   |====|
  |                        |==== GLYbmumu
  |
  |                    syst|==== GLYa1rano
  |                   |====|
  |                998|    |==== GLYa1mumu
  |           859|====|
  |         |====|1000|========= GLYa1hosa
  |         | 994|
  |      942|    |============== GLYa1dare
  |    |====|
  |    | 988|           985|==== GLYa3hosa
  |    |    |==============|
  |1000|               1000|==== GLYa3rano
  |====|
   1000|======================== GLYa4mumu
       |
       |           999|========= GLYa2hosa
       |==============|
                  1000| 965|==== GLYa2rano
                      |====|
                        863|==== GLYa2mumu
\
|
| beta
|
/

\
|
|
| alpha1
|
|
/

\
| alpha3
/

  alpha4

\
|
| alpha2
|
/

Comments

Because of α4, M4 region is not taken into account,hence the small length of the alignment.

New Subfamily of Subunits

(Only in C. elegans so far.)

Alignment

11 sequences, 218 positions. Outgroups are human Lymnea GABA α1 and β1 subunits.

Results

Upper-level

                   965|==== GABf58g6_4cael
            |=========|
            |      985|==== GABf47a4_1cael
         984|
       |====|      862|==== GABk10d6_1cael
       |1000| 951|====|
       |    |====| 984|==== GABc53d6_3cael
    343|      797| 
  |====|         |========= GABf55d10_5cael 
  | 666|
  |    |=================== 5HTmod1cael
  |    |
  |    |=================== GABt20b12_9cael 
  |
  |                926|==== GABf09c12_1cael
  |===================|
                   992|==== GABt21f2_1cael
                   

Anionic Glutamate Receptor Subunits

Alignment

9 sequences, 332 positions. Outgroup is Lymnea GABA ζ subunit.

Results

Upper-level

              686|==== GLUcl3cael
            |====|
         463| 674|==== GLUclacael
       |====|
       | 864| 999|==== GABgbr2cael
       |    |====|
       |      994|==== GLUclxonvo
    644|
  |====|     1000|==== GLUclbcael
  | 577|=========|
  |    |     1000|==== GLUclbhaco
  |    |
  |    |============== GABc27h5_4cael 
  |
  |=================== GLUcldrme

Comments

The subunit "GAB"gbr2cael is probably the true ortholog of GLUclxonvo, rather than the so-called GLUclxcael, much more divergent (not shown here).


Related Bibliography

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

In the article quoted above, there was certainly a confusion between the delta and dzeta subunits.

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

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