ENCODE and the Truth
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transcribed pseudogenes might regulate protein production through various RNA-based silencing processes.
They then demonstrated that some pseudogenes had a biological effect. In one case a pseudogene produced specific RNAs that controlled the growth of tumors.
Pseudogenes with actual biological functions? According to Graur, a pseudogene is by definition not functional. Graur tries to argue around this, saying these are not “real” pseudogenes but are pseudogene “look-alikes”.
Sounds like an ad hoc hypothesis to me, moving the goalposts after the ball is in the air. “Pseudogenes have no function.” “How about this one that does?” “It is a not a ‘real’ pseudogene. It is a pseudogene look-alike.”
Maybe. But which proponent – Graur or ENCODE – would even have looked in the first place?
Functional pseudogenes are not just a “measly” one-hit wonder. Let’s just look at some papers that have come out in February. One describes a database of transcribed pseudogenes, identifying short RNAs that could not only inhibit protein production but also increase it.
How about this paper – using the ENCODE database – finding that several genes, including a pseudogene, may have “evolved under purifying selection, suggesting that their roles are essential and non-redundant?”
A pseudogene that is not translated into protein, that was actively selected and is essential. Found with the help of the ENCODE database.
Then there is this paper entitled “A pseudogene long-noncoding-RNA network regulates PTEN transcription and translation in human cells.”
The transcribed RNA from this pseudogene binds to mRNA – causing degradation similar to Chan. It also binds to the working gene’s DNA causing epigenetic changes.
One pseudogene with multiple biological functions.
This report’s lead author – Kevin Morris – said (my bold):
“Importantly, the observations presented here tell us that some long non-coding RNAs (thought to be junk), in this case emanating from a pseudogene, are mechanistically relevant and act, in the case of PTEN, as a master regulator of both transcription and translation. It shows that long-non-coding RNAs, even though not conserved, have a great potential to evolve into important regulatory units and have been overlooked as a major mechanistic player in human cells.”
A follower of Graur likely would not have supported these projects. Because they are sure that non-coding, non-conserved biologic fossils such as pseudogenes have no function.
And that decision would have been wrong.
Non-conserved, non-coding pseudogenes could be major players in human cells. How often does this happen? We do not know yet.
But when we look, we find them.
Openhelix suggests that the value of ENCODE is its database which can now be examined for the gold that exists there. A database that might not exist if the Graur view prevailed.
ENCODE’s definition provides us with the impetus to find out if a pseudogene is functional. Graur does not.
The Graur definition hampers further investigations, suggesting that we should not even look because the answer is already known.
ENCODE is most likely not fully correct. That is why its work is put out there. We need to know how it withstands the onslaughts of public examination – such as Graur – to see where its faults lie.
But it appears to me that Graur has already been shown to be faulty. Transcription alone – from a nonfunctional, non-coding, non-conserved protein gene – can have huge biological ramifications.
I wonder whose view of pseudogene function Feynman would have suggested leads to cargo cult science? Which one has its view of rightness clothed in supposed superiority?
Which one more greatly limits further exploration because of surety that does not really exist, and which one drives further exploration?
ENCODE’s view will likely be altered as we learn more. That is how science usually works.
And in a few years the authors of Graur might wish that their paper had shown a little more humility, a little less personality and a little less snark. As I said, there are reasons why research papers are so dry.
Scientists use the passive voice and an impersonal approach in research discussions for a simple purpose – to provide personal distance from the scientific models they describe. Impersonal descriptions make it easier to separate personality from the research, especially if one is eventually shown to have used an imperfect model.
Temporary fame and excitement do not long hide incorrect science. Anyone can propose an imperfect model, can fool themselves, and can be shown by Nature to be wrong.
Nothing reveals an a-hole faster than being on the wrong side of Nature. No one wants that reputation.
Thus, we write “The work was done” rather than “I did the work.” It’s easier to say “The research was incorrect” than “I was wrong.”
Because Nature is always right.
The truth will come out.