Another Step in the Evolution of Humans and Apes from Ancestral Mammals

One of the most fascinating lines of research within the field of evolutionary biology is the search to find the genes that changed at the split between ancestral mammals and our own closer ancestors, the great apes.

In a fascinating new study in the August 8th edition of PLoS Genetics, Lia Rosso and colleagues have detailed specific changes in a single duplicated gene in apes and humans. Their data reveals what may be a common path for evolution: duplication of a gene with a specific function, a change in the duplicate that allows it to change its location within the cell, and further changes in the specific function of that gene.

There are several interesting things that I took from this study. First, the genes they study are GLUD1 and GLUD2, enzymes involved in glutamate metabolism, which in itself is less interesting to me (just a personal disinterest in metabolism - no offense to you metabolism folks). What's simply astounding to me is the method through which the second gene came about - a method of duplication I sometimes forget.

GLUD1 is present in all mammals, while previous research has shown that GLUD2 arose through an amazing process of duplication that departs from the simple genomic duplication methods we often think of.

Here's a quick primer for you non-biologists that will help you understand. Most vertebrate genes are actually broken up along a strand of DNA. That is, there are sequences (called introns) within the gene that are not involved in coding for the gene's protein.

Imagine that this sentence is a gene: BIOkzkfkjLOGYskrzsISkzskjzsCOgkttkzjOL.
In this case, imagine that the product of the gene is "BIOLOGY IS COOL".
The gobbledegook between and within the words are the introns that are cut out before the product is made. The question of why the nonsense sequences are even there is a whole other story that we won't consider here.

OK...so now we have our gene - let's call is BioCool1.

One other point you must know - DNA genes are read and "transcribed" to RNA, which serves as a "message". The RNA message is then read to make the protein. Okay?

When the BioCool1 gene is transcribed to RNA (which is then used to make the protein), those nonsense gobbledegook introns are removed so that there are now RNAs floating around the cell that read "BIOLOGY IS COOL", without the nonsense introns.

Now, you may have heard of some viruses called "retroviruses", such as HIV. That means that they have enzymes that can take their viral RNA genome, "reverse transcribe" their genome into DNA, and then insert the DNA version of their genome into our own genome. Thus these viruses make themselves a part of the host organism, and the host genome now produces tons of viral RNA and proteins.There are more levels of complexity in this, but to keep it simple we'll just consider retroviruses.

Imagine if those viral enzymes take that BioCool1 RNA with the introns cut out, turn it into DNA, and then insert it back into our own DNA genome. What we have now are TWO versions of the BioCool gene DNA in our genome: the original BioCool1 (which has all the nonsense sequence within it, and a new version, BioCool2 (which only has the "BIOLOGY IS COOL" sequence).

Well, this is how GLUD2 was originally made in ape and human ancestors from the GLUD1 gene. Pretty amazing, no?

What the above researchers further showed is that while GLUD1 protein can be found in multiple places in a single cell (in the mitochondria and cytoplasm), GLUD2 underwent a single amino acid change that made the protein stick only to the mitochondria. Using sophisticated analyses, they showed that this change occurred soon after the gene was duplicated 18-25 million years ago, and that the change was then positively selected for (meaning that animals with the change were somehow "more fit" than other individuals). The gene concurrently underwent further changes that altered the specific function of the protein, and it is suggested that the changes were involved in brain function (specifically in metabolism of the neurotransmitter glutamate).

So...in summary, this study reminds us of a pretty cool mechanism for duplicating a gene and positively selecting it for function in specific subcellular locations, and it gave us one more glimpse into the changes that have resulted in the evolution of the amazing complexity of the human brain.

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image from psychology.wikia.com