That Subtle Frontloading Pattern Again

Let me show you another example of that subtle front-loading pattern.  This time, we’ll use a published paper that discusses a protein I have previously tagged as a candidate for front-loading:

Pincus D, Letunic I, Bork P, Lim WA. 2008. Evolution of the phospho-tyrosine signaling machinery in premetazoan lineages.  Proc Natl Acad Sci U S A. 105(28):9680-4.

Pincus et al. set out to explain the origin of the 3-part tyrosine kinase system as illustrated below:

I have already briefly discussed this system and its relation to front-loading.  In this study, the researchers looked for evidence of the writer, reader, and eraser among choanoflagellates, fungi, and a slimemold and reported their results in the following figure:

As you can see, they found the eraser and reader in fungi and slimemold, but not the writer (tyrosine kinase).  And once the writer appeared, there was a burst in the number of all three components.

However, note from the phylogenetic tree above that the researchers propose the origin of the writer  just prior to the split between choanoflagellates and metazoans.  This is not a big problem for front-loading, as it would be easy to front-load the appearance of this writer by endowing life forms with serine/threonine kinases.  Nevertheless, the case for front-loading would be stronger is the tyrosine kinases were much older and closer to the original cells.  What’s more, way back in 2002, I predicted:

my working hypothesis (just recently being seriously entertained) is that the original cells were front-loaded to make it more likely that multicellular states would evolve. These leads me to predict that we will find remnants or “fossils” of such front-loaded distributed among protozoa. Specifically, we will find various pieces of information, necessary for multicellular life, not necessary for single-celled existence, yet still present in many single-celled organisms. {emphasis added)

So are the researchers correct in dating the origin of tyrosine kinases just prior to the split between choanoflagellates and metzoans?  Or was yours truly correct in expecting them to be older, and thus more widely distributed?

Consider the findings of another research paper: Genome Analysis of the Unicellular Green Alga Chlamydomonas reinhardtii Indicates an Ancient Evolutionary Origin for Key Pattern Recognition and Cell-Signaling Protein Families, by Glen L. Wheeler, Diego Miranda-Saavedra and Geoffrey J. Barton.  Genetics 179: 193–197 (May 2008).

Here is one finding:

Chlamydomonas therefore contains a full complement of the phosphotyrosine-signaling tool kit as found in metazoans and choanoflagellates (King et al. 2008). The discovery of TKs, SH2 domains, and PTPs in chlorophyte algae and land plants suggests that phosphotyrosine signaling mediated by TKs is of general importance in photosynthetic organisms and represents an ancestral mode of cellular signaling.


The identification of such a large family of putative TKs in Chlamydomonas supports the hypothesis that phosphotyrosine signaling appeared early in eukaryote evolution before the divergence of the Opisthokont lineage.

So let’s bring back our eukaryotic tree:

Chlamydomonas is a member of the chlorophytes (also known as green algae) found in the upper left green panel.  That Chlamydomonas contain a full complement of the phosphotyrosine-signaling tool kit tells us that the tool kit is much older than Pincus et al. inferred.  In fact, tyrosine kinases probably exist in Tetrahymena, a member of the group known as ciliate in the above tree (lower left pink panel):

Bartholomew J, Reichart J, Mundy R, Recktenwald J, Keyser S, Riddle M, Kuruvilla H. 2008. GTP avoidance in Tetrahymena thermophila requires tyrosine kinase activity, intracellular calcium, NOS, and guanylyl cyclase. Purinergic Signal. 4(2):171-81.

Guanosine 5′-triphosphate (GTP) is a chemorepellent in Tetrahymena thermophila that has been shown to stimulate cell division as well as ciliary reversal. Previous studies have proposed that GTP avoidance is linked to a receptor-mediated, calcium-based depolarization. However, the intracellular mechanisms involved in GTP avoidance have not been previously documented. In this study, we examine the hypothesis that GTP signals through a tyrosine kinase pathway in T. thermophila. Using behavioral assays, enzyme immunosorbent assays, Western blotting, and immunofluorescence, we present data that implicate a tyrosine kinase, phospholipase C, intracellular calcium, nitric oxide synthase (NOS) and guanylyl cyclase in GTP signaling. The tyrosine kinase inhibitor genistein eliminates GTP avoidance in Tetrahymena in behavioral assays. Similarly, pharmacological inhibitors of phospholipase C, NOS, and guanylyl cyclase all eliminated Tetrahymena avoidance to GTP. Immunofluorescence data shows evidence of tyrosine kinase activity in the cilia, suggesting that this enzyme activity could be directly involved in ciliary reversal.

In fact, another paper detected the existence of an tyrosine kinase receptor in Tetrahymena that responds to human insulin: Christensen ST, Guerra CF, Awan A, Wheatley DN, Satir P. 2003. Insulin receptor-like proteins in Tetrahymena thermophila ciliary membranes. Curr Biol. 13(2):R50-2.

So once again, we can hear that echo of front-loading. Tyrosine kinases play a very important role in complex animals.  But it doesn’t seem all that important to fungi and single-celled organisms, given its rarity among these groups.  Yet the enzyme apparently arose with the origin of eukarya itself given its widespread distribution.  In other words, it is ancient, but did not become important until long after it arose.

2 responses to “That Subtle Frontloading Pattern Again

  1. lol you had already discussed the paper I referenced. Always one step ahead of me.

  2. Pingback: Incurring the Cost «

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