Pseudo Goes to Work

In the previous posting, I tried to help you visualize pseudogenes from a teleological perspective, demonstrating that the non-teleological perspective is not necessary.  Let’s take it a step further.

Pseudogenes are sequences of DNA that are similar to functional genes, but have acquired defects that prevent the expression of functional products. Such sequences are generated by gene duplication, where one duplicate undergoes some lesion that is not selected against. As a result, the defective gene (now a pseudogene) may continue to undergo further mutational insult, effectively causing it to decay into oblivion over time.

Yet because the cellular architecture entails that an “RNA world” exists in parallel with a “protein world,” might many of these pseudogenes simply be genes escaping the constraints of the protein world in order for the opportunity to more fully participate in the RNA world?

A few years back, a study of human chromosome 22 identified 525 pseudogenes. [1] Remarkably, the study found about 20% of these pseudogenes to be transcribed, such that the RNA products were continuously synthesized. Might some of these RNA be fishing for a function?

At this point, let’s turn to the snail Lymnaea stagnalis. It expresses a nitric oxide synthase (NOS) pseudogene in its central nervous system. [2] Better yet is that the pseudogene is co-expressed with the normal NOS gene in a particular set of neurons. The researchers who made this discovery were able to show that the NOS pseudogene RNA and the NOS gene RNA were able to form an RNA-RNA duplex that inhibits translation. In other words, the pseudogene is acting as natural anti-sense RNA to regulate expression of the NOS gene downstream of transcription. Since nitric oxide, the product of NOS, is a neurotransmitter, this raises the possibility that this pseudogene can play an important role in the central nervous system. And indeed, a more recent study has shown that this pseudogene is involved in nothing less than learning and memory [3].

In my opinion, pseudogenes exist on a continuum of function, where at one end many have become completely functionless and are in a true process of decay, while at the other end others may function similarly to the NOS pseudogene and play significant roles in physiology or development. In between, we have the pseudogenes that may simply be tweaking regulation or enhancing evolvability.

Here again we see the reach of gene duplication, a biological process that not only sends out “feelers” for evolution, but amplifies the regulatory possibilities for an evolving system. As for brains, maybe one day we will find that a human pseudogene makes it possible for you to read and understanding what I am writing.

1. Zheng D, Zhang Z, Harrison PM, Karro J, Carriero N, Gerstein M. 2005. Integrated pseudogene annotation for human chromosome 22: evidence for transcription. J Mol Biol. 349:27-45.

2. Korneev SA, Park JH, O’Shea M. 1999. Neuronal expression of neural nitric oxide synthase (nNOS) protein is suppressed by an antisense RNA transcribed from an NOS pseudogene. J Neurosci. 19:7711-20.

3. Korneev SA, Straub V, Kemenes I, Korneeva EI, Ott SR, Benjamin PR, O’Shea M. 2005. Timed and targeted differential regulation of nitric oxide synthase (NOS) and anti-NOS genes by reward conditioning leading to long-term memory formation. J Neurosci. 25:1188-92.

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3 responses to “Pseudo Goes to Work

  1. As a result, the defective gene (now a pseudogene) may continue to undergo further mutational insult, effectively causing it to decay into oblivion over time.

    Perhaps these are not “pseudo” anything, because they do not “decay into oblivion”. (if they did “decay into oblivion” we wouldn’t make the connection to a transcribed gene)

    But anyway, what if the evolutionary perspective is keeping us from understanding the role of RNAs- designed RNAs for regulatory and house-keeping functions.

    IOW by focusing on the “pseudo-gene” aspect we may be missing a huge hunk of the overall picture.

  2. A few years back, a study of human chromosome 22 identified 525 pseudogenes. [1] Remarkably, the study found about 20% of these pseudogenes to be transcribed, such that the RNA products were continuously synthesized. Might some of these RNA be fishing for a function?

    So is the evolutionary story that these alleged pseudo-genes “just happened” to also code for those RNA products?

    What happened to critical thinking and rationality?

  3. OK back to the RNA fishing expedition, two words-

    Targeted search

    Intial conditions, target conditions, means to an end.

    FLE in a nutshell…

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