Urea cycle in diatoms

Building on that work, Allen and colleagues explored the evolutionary history of diatoms, specifically P. tricornutum, and cellular mechanisms for nutrient utilization in the environment, leading to the finding that diatoms have a functional urea cycle.

This was a stunning discovery, says Allen, because it was thought that the urea cycle originated with the metazoan (animal) branch of life.

There it has played an important role in facilitating a wide range of physiological innovations in vertebrates.

For example, urea synthesis enables rapid control of minerals and salts in the blood in animals such as sharks, skates, rays and bony fish, and ammonia detoxification associated with water retention in amphibians and mammals.

The latter was likely a prerequisite for life on land, and subsequently enabled the biochemical pathways necessary for processing a high-protein diet.

Allen and others have now shown that the urea cycle originated hundreds of millions of years before the appearance of metazoans.

HERE

More Epithelial Nudging

If you’ll recall, back in December, I provided evidence that unicellular organisms were endowed with components (beta catenins) that served as preadaptations to nudge epithelial tissue into existence when needed.

Well, feast your eyes on a paper that was published in Science just a couple of weeks ago.

Welcome to the Party

For several years now, I have been asking “where are the prokaryotic mice?”  Given that the prokaryotic cell plan is the most ancient, abundant, and successful cell plan on earth, why hasn’t the blind watchmaker been able to craft together the convergent equivalent of some metazoan?  In fact, as I noted, “had the eukaryotic cell design failed to emerge, the Earth would contain nothing more complex than any extant bacteria in existence today.”   Then, back in October 2010, a paper from Lane and Martin was published that supports my contention:

Our considerations reveal why the exploration of protein sequence space en route to eukaryotic complexity required mitochondria. Without mitochondria, prokaryotes—even giant polyploids—cannot pay the energetic price of complexity; the lack of true intermediates in the prokaryote-to-eukaryote transition has a bioenergetic cause.

A few days ago, biologist PZ Myers recently helped to popularize Lane and Martin’s paper and begins by essentially asking…you guessed it…”where are the prokaryotic mice?”

Myers writes:

Nudging beta catenins to emerge

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 eukaryotic cell: Preadapted for multicellular existence

First, a review.

We’re looking at two different eukaryotic proteins: beta catenin and alpha importin. Beta catenin plays two different crucial roles in metazoan life: 1) It is a key component of the adherens junction which connects cells together and 2) it is involved in the transcription of genes that play an important role in the development of the embryo and the maintenance of organs. This is a neat example of one protein playing two important roles in metazoan life. A simplified figure is shown below, where the beta catenin is represented by the pink circle:

Next are the alpha importins. They transport proteins into the nucleus through the nuclear pore complex. The figure below shows the basic mechanism involved:

The alpha importin is shown in blue. It recognizes and binds the nuclear localization signal (NLS) on a protein that is destined for the nucleus (in the above figure, it is the experimentally designed radioactive protein) and then binds with another protein, beta importin, to be transported into the nucleus.

It is my hypothesis that the alpha importins imposed a form of guidance to evolution by front-loading the eventual emergence of the beta catenins which would, in turn, facilitate the evolution of metazoa. The first line of support for this hypothesis would be to show a homologous relationship between these two different proteins (and as far as I have been able to tell, no one has seriously proposed this). So allow me to make that case.

Another deep, homologous relationship

I have previously tried to show you that it is quite plausible to propose that a protein essential in two multicellular processes existed in the last common ancestor of all eukaryotes. Thus, this could be one front-loaded feature to these cells that would, sooner or later, help to nudge animal life into existence.  But if it is too difficult to believe that something like beta-catenin is as old as the eukaryotic cell itself, let me make it even more clear that beta-catenin was always in the cards.  How?  By showing you that even if beta-catenin is not quite as ancient as I propose, its very existence was front-loaded by the existence of a remarkably similar homolog – alpha importins.

Aardvark

One of the organisms that has a homlog to the Volvox version of beta-catenin is Dictylostium, otherwise known as a slime mold. This organism normally exists as single-celled amoeba, but when stressed, the cells seek each other out to form a multicellular state that looks like a slug, where all cells coordinate with each other for motility and reproductive purposes.

Below is a figure of the lifecycle of this organism:

As you can see, this organism can exist in an amoeboid state, a flagellated state, a multicellular state that mimics slugs and fungi, and as a spore. It even undergoes meiosis. All that biotic diversity packed into a single genome.

Here is a nice video that allows you to see this creature in action:

As mentioned before, the homologs to the Volvox version of beta-catenin are mostly annotated as hypothetical proteins because they were identified from DNA sequence rather than biochemical or genetic screens. Not so with Dictylostium. Its homolog is known. And has been studied. It’s called aardvark.

The Adherens Junction Homology Goes Deep

Now that we have seen that VOLCADRAFT_41528  (from Volvox carteri ) is likely to be homologous to human beta catenin, it becomes reasonable to propose that something very similar to beta-catenin existed in the last common ancestor of all eukaryotes.

However, if we are going to make this rather radical claim, it would help if we could find homologs in other lineages.  So let me begin by pointing out that homologs of human beta catenin exist in all three basal metazoan lineages: Trichoplax, sponges, and comb jellies.  Among metazoans, the beta catenin sequence is strongly conserved.  For example, 340/592 (58%) of the positions have identical amino acids when sponge sequence is aligned with human sequence.

So beta-catenins are universally present among metazoans and found in the multicellular algae, Volvox.  But what about true unicellular organisms?

If you go back to the table I posted a few days ago, we do have one such example – Trypanosoma brucei, a protozoan that causes African sleeping sickness, has a protein that has similar amino acids in 90/204 (45%) positions.  But the E value for this match is only 2.00E-06.  Smaller than 1e-04, but not that much.  The bunnah wants more crunch in his carrot.

To better resolve this issue, I simply took the next logical step – I used the Volvox homolog to BLAST other green algae and various protozoan lineages.  The results are shown in the below table:

A Homologous Relationship

Let’s take a few moments to show you that the green algae, Volvox carteri, contains sequence that apparently codes for a homolog of the human beta-catenin protein.

If you take the sequence from the human beta-catenin gene (CAA61107.1) and use it to BLAST the genome of Volvox carteri, you will retrieve “hypothetical protein VOLCADRAFT_41528 [Volvox carteri f. nagariensis]” (XP_002955847.1)

Now, human beta-catenin is 781 amino acids in length while the Volvox protein is 525 amino acids.  The BLAST program is able to align the sequences such that sequence of the entire Volvox protein is matched up against human beta-catenin starting around amino acid position 150.  When this is done, 144/536 (27%) of the positions are identical and 238/536 (45%) positions contain amino acids that have similar properties.  Given the phylogentic distance between these two species, that is pretty impressive.  Could it be simple coincidence that these positions match up like this?  No.  The  E value associated with this match is 1e-25.  The BLAST program is designed such that matches with E values less that 1e-04 are not attributed to chance.  This is why biologists infer homology when the E value is that small.  And given that 1e-25 is smaller than 1e-04 by several orders of magnitude, we can safely assume these two sequences are homologous.

But it actually gets better than this.

Gold in dem holes?

Me thinks da bunny has dug up a little goldmine. In the previous essay, I shared what I uncovered about the components of adherens junctions. So let’s get up to speed about these structures. I told you they are used to connect cells together to form the sheets of cells known as epithelial tissue. Here are some more facts about these structures:

Adherens junctions provide strong mechanical attachments between adjacent cells.
• They hold cardiac muscle cells tightly together as the heart expands and contracts.
• They hold epithelial cells together.
• They seem to be responsible for contact inhibition.
• Some adherens junctions are present in narrow bands connecting adjacent cells.
• Others are present in discrete patches holding the cells together.

Adherens junctions are built from:
• cadherins — transmembrane proteins (shown in red) whose
o extracellular segments bind to each other and
o whose intracellular segments bind to
• catenins (yellow). Catenins are connected to actin filaments

[Source]

Now, as I have shown, all the major components of these structures that are used to form multicellular organisms have homologs that exist in unicellular organisms. But the most interesting finding is the homolog for human beta-catenin in the green algae, Volvox carteri. Volvox is a actually a multicellular organism,

a fact that is going to make this rabbit hole very interesting later on.