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Science

Cross-Confirming Great Ape Divergence Times by Dating Processed Pseudogenes

From: Ration alMind 
This is a repost of an article I first wrote up last year on my own blog.

 

I’m sure most of you are already pretty familiar with pseudogenes – they can be considered “vestigial” genes because they’ve lost their original protein-coding function, and are often totally non-functional.

Processed pseudogenes are a specific kind of pseudogene that has been produced through the action of reverse transcriptase. A functional protein-coding gene is transcribed into pre-mRNA, and then processed into mRNA, during which time the introns of the gene are spliced out to leave the exons, and a poly-A tail is added, which is a literally a long sequence of adenine nucleotides added to the back end of the mRNA sequence. I won’t go into the function of the poly-A tail here, all you need to know for now is that it is added.

splice
Overview of how to produce proteins from genes.

If an enzyme called reverse transcriptase encounters the processed mRNA before it can be translated, a DNA copy of the mRNA will be produced. This DNA copy is identical to the original gene that produced the mRNA for the most part, but with a few key differences, for example: it lacks introns, because they were spliced out during processing of the pre-mRNA, and it will have a poly-T tail on the end of the sequence, complementary to the poly-A tail on the  mRNA.

This DNA copy can then be integrated at a random location in the genome of the host cell, and this is what is called a processed pseudogene (PP). It has no introns and a poly-T tail – because of this, it can be easily distinguished from its “parent gene”. Because the PP can be integrated into the host genome pretty much in a random location, it’s very unlikely to end up downstream of regulatory sequences such as promotors, so it’s unlikely to be transcribed and serve any kind of function. Therefore, most PPs are completely non-functional.

As PPs tend to be non-functional, they are under no selection pressure to maintain their precise sequences so they accumulate random mutations over generations, and because the mutation rate can be estimated, it’s actually possible to estimate the “age” of the PP based on how mutated it has become since it was inserted into the genome by comparing it to the sequence of its “parent gene”. By calculating the age of the PP, predictions can be made about which organisms should share the pseudogene if common ancestry is true. For example, if a Human PP is calculated to be older than about 6-8 million years, then we would expect to find the PP in Chimpanzees as well, because that’s when the common ancestor of Humans and Chimps lived, so we would expect it to have originated in them, meaning that both the descendent lineages: Humans and Chimps, should have inherited it.

This test was carried out by Friedburg and Rhoades in 2000, on six PPs: an alpha-Enolase PP; two calmodulin II (CALM II) PPs; and three argininosuccinate synthetase (AS) PPs. Their analysis is summarised in the following table:

Screen Shot 2016-08-10 at 18.14.05
The headings on the top of the columns show which organism was tested for the presence or absence of each of the the processed pseudogenes from the left-hand columns. Underneath these headings are the estimated divergence times between the human lineage and the lineage of that organism, based on previous calculations. Underneath each of the pseudogene names on the left-hand side, the estimated age of the PP is listed, having been calculated based on their accumulated mutations. A plus represents the presence of the PP, while a dash represents the absence.

As you can see, the pattern of presence and absence of the PPs in the various organisms matches up almost perfectly with their apparent age. You don’t see any examples of a PP being present in a lineage that supposedly diverged before the PP was integrated into the host genome, for example the alpha-Enolase PP is estimated to be 11 million years old, and as a result it isn’t present in Orangutans, as they are estimated to have diverged 16 million years ago.

The only imperfection in this data is the fact that one of the AS PPs doesn’t seem to be present in Gorillas, despite the fact that its age would suggest that it should be, and the fact that it’s present in an “older” lineage – Orangutans. There are two primary possible reasons for this: it doesn’t show up in the PCR screening because it happens to have been deleted in the Gorilla lineage, or it doesn’t show up because it has been mutated in such a way that the PCR primers designed to amplify the DNA sequence could no longer recognise the PP.

This study, and another similar one performed by the same researchers in 2002 on Murine Rodents provide yet another demonstration of the predictive and explanatory power of the Theory of Evolution and Common Descent.

Comments and queries are welcome.

-RM

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