Adherens junctions poised to appear

In the previous posting (which was originally posted over a year ago), I was able to track down some papers which uncovered evidence for the existence of various adherens junctions proteins in unicellular organisms.  Well, a few days ago, I had the time to probe databases with sequence from human genes in search of homologs for adherens junction proteins in unicellular organisms.

Recall the basic components of an adherens junction as seen in the below figure:

As you can see, the cadherin is the membrane protein used to link cells together. The cadherin, in turn, is linked to the cytoskeletal microfilaments through a complex composed of beta-catenin, alpha-catenin, alpha-actinin, and vinculin.

Below is a table that lists what I found.

The human gene used to search is listed on the left, while the right hand columns list the organism that contained a match, the fraction of amino acid positions in the match that contained similar amino acids and, most importantly, the E value.  The E value is a statistical measure where the rule of thumb is that E values less than 10^-4 mean the similarities between the two sequences cannot be attributed to chance.  Thus, biologists infer homology if the values are less that 10^-4.

Human protein Human gene Unicellular species % positives E value
Actinin, alpha 3 AAA51585.1 Monosiga brevicollis 579/894 (65%) 0
Actinin, alpha 3 AAA51585.1 Dictyostelium discoideum 509/868 (59%) 7.00E-163
Actinin, alpha 3 AAA51585.1 Polysphondylium pallidum 500/866 (58%) 9.00E-153
Actinin, alpha 3 AAA51585.1 Entamoeba histolytica 217/352 (62%) 1.00E-77
vinculin isoform VCL AAA61283.1 Monosiga brevicollis 235/503 (47%) 6.00E-36
vinculin isoform VCL AAA61283.1 Polysphondylium pallidum 205/455 (46%) 4.00E-13
vinculin isoform VCL AAA61283.1 Dictyostelium discoideum 57/109 (53%) 1.00E-07
catenin beta-1 CAA61107.1 Volvox carteri 238/536 (45%) 1.00E-24
catenin beta-1 CAA61107.1 Trypanosoma brucei 90/204 (45%) 2.00E-06
catenin alpha-1 BAA02979.1 Monosiga brevicollis 305/756 (41%) 9.00E-2

So what are these organisms?  Below is a phylogenetic tree that shows their relationship to metazoans:

If we combine this tree with the table, we can see that alpha-actinins and viniculins existed long before metazoans came onto the scene, before fungi and metazoans split.

The beta-catenins are found in green algae (Volvox), indicting that they existed in the last common ancestor of green algae/plants and animals.  So far, the alpha catenins and cadherins appear to be restricted to choanflagellates and metazoans.

The bottom line here is that homologs for all components of the adherins junction existed long before the simplest of metazoans came into existence (even though no single celled organism in particular contains all components).  Thus, the information was there to nudge the appearance of adherens junctions into existence when it came time for metazoans to appear.

I would also add there are many reasons to think the table listed above underestimates the extent to which these homologs are present among unicellular organisms:

1. I only used the sequence for one human gene for each of these components to search the data bases.  A more wide-reaching approach would be to include sequence from various other metazoans as a probe.

2. I only searched the genomes of Monosiga, amoeboids, green algae, kinetoplastids, and Tetrahymena.

3. I used the standard BLASTP to search instead of the more sensitive PSI-BLAST.

4. We posses only a tiny fraction of all single-celled eukaryotic sequence

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2 responses to “Adherens junctions poised to appear

  1. Pingback: Gold in dem holes? |

  2. Pingback: The Adherens Junction Homology Goes Deep |

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