Another brain protein with deep homology

Here is something that is pretty neat:

The size and shape of the human cerebral cortex, an evolutionary marvel responsible for everything from Shakespeare’s poetry to the atomic bomb, are largely influenced by mutations in a single gene, according to a team of researchers led by the Yale School of Medicine and three other universities.

The researchers found that mutations in the same gene, centrosomal NDE1, which is involved in cell division, were responsible for the deformity.

“The degree of reduction in the size of the cerebral cortex and the effects on brain morphology suggest this gene plays a key role in the evolution of the human brain,” said Murat Gunel, co-senior author of the paper and the Nixdorff-German Professor of Neurosurgery and professor of genetics and neurobiology at Yale.

“These findings demonstrate how single molecules have influenced the expansion of the human cerebral cortex in the last five million years,” Gunel said.

So here is a gene, Nde1, that has played a key role in the enlargement of the brain during human evolution.  As the article notes, Nde1 is part of the centrosome, an organelle that functions to organize the microtubules throughout the cell.  The function of Nde1 is not well characterized, but it is known to play a role in mitosis and neuron migration.  So it makes sense that a crippled version of Nde1 might exhibit deficient levels of cell division and neuron migration, explaining the small brained phenotype.

So when did Nde1 arise?

It is a centrosomal protein, but centrosomes are complexes made up of many proteins.  As such, Nde1 might have been recruited to the centrosome long after the centrosome existed.  So again, when did Nde1 arise?  When this question is asked, we immediately see that the non-teleological perspective provides no guidance.  This is because this perspective easily incorporates any time of appearance.  It could have arisen with the origin of primates, the origin of mammals, the origin of vertebrates, chordates, metazoa, etc.  The non-teleological template would easily absorb any such origin date.  In fact, if we were to go out on a limb and make a prediction from within the non-teleological perspective, we would probably predict that Nde1 arose about the same time as nervous tissue did.  This is what we would expect from the hypothesis of co-evolution.

However, if we propose that something akin to a human-like brain was front-loaded to appear, then we would predict Nde1 to be very ancient.  The hypothesis of front-loading is not nearly as plastic as the non-teleological perspective.

To test this, let’s use the human sequence of Nde1 to probe the genomes of the basal metazoans – sponges, jellyfish, comb jellies, and placozoa.  When this is done, something interesting happens.

Both jellyfish and placozoa have very strong homologs of human Nde1 (although both are annotated a predicted proteins).  The Nematostella vectensis protein has 59% sequence identity with an E value of 2e-81.  The Trichoplax adhaerens protein shares 42% sequence identity with an E value of 7e-55.

Yet none of the genomes from sponges or comb jelly have a homolog to human Nde1.

This pattern clearly does not support this protein as co-evolving into existence with neurons, as comb jellies have nervous tissue and no Nde1 while Trichoplax has an Nde1 homolog and no nervous tissue.

So the Rabbit wants to dig deeper.  And sure enough, a solid homolog of Nde1 exists among the filamentous fungus (Nud).  In fact, this is where Nde1 was first discovered, as Nud is a Nuclear distribution protein.  And if we dig deeper yet, there is another solid homolog in slime molds known as the Lis-interacting protein from Dictyostelium discoideum.  It shares a 30% sequence identity with human Nde1 with an E value of 6e-25.  However, I could find no homologs among the green algae and ciliate genomes.

It becomes even more interesting if the human Nde1 sequence is used to BLAST plant genomes.  No plant genome has a homolog except one,  Hordeum vulgare

Hordeum vulgare is considered the wild ancestor of barley.  This plant gene shares 36% sequence identity with human Nde1 with an E value of 2e-33.  It thus becomes possible that an Nde1-like protein existed in the last common ancestor of all plants and was lost in many lineages.

So Nde1, which appears to have played a key role in the evolution of the human brain, is a centrosomal protein that is ancient, dating back at least to the last common ancestor of slime molds and fungi.  It may even go back to the last common ancestor of metazoans, plants, and fungi.  Clearly, we are in the realm of single-celled organisms.

It has apparently been lost in many protozoan and plant lineages.  So it’s not essential to life as a protozoan or plant or sponge or comb jelly. It is very common in fungi and it’s not until we get to the nematodes, arthropods, and chordates does it become common among metazoans.

So once again, we find a protein that has some utility among single-celled life forms and simpler multicellular states, but it does not become crucial until it is time to either live as a filamentous fungus or an animal with a developed nervous system.  And then later, it becomes essential for the evolution of large brains.  And that makes the Rabbit smile.

3 responses to “Another brain protein with deep homology

  1. If no homolog to Nde1 is found in bacteria, is your hypothesis (that life was front-loaded for human brain evolution) weakened?

  2. The presence of a Nde1 paralog, Ndel1, probably influences how Nde1 confers ‘human’ like characteristics to the brain. And this paralog is not present in most of the lower organisms you mentioned. So in higher organisms it’s an additive effect.

  3. Yet it is a paralog of Nde1. I have long argued about the important role of gene duplication in front-loading.

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