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Pseudogenes: Newly Discovered Players in Human Cancer


A recent paper in Science offers an excellent review of the “broad and multifaceted spectrum of activities in human cancer” played by pseudogenes. I intend to review the paper for Evolution News & Views so I will reserve my more detailed comments for there. Here, I offer a couple of highlights.

From the abstract:

Because they are generally noncoding and thus considered nonfunctional and unimportant, pseudogenes have long been neglected. Recent advances have established that the DNA of a pseudogene, the RNA transcribed from a pseudogene, or the protein translated from a pseudogene can have multiple, diverse functions and that these functions can affect not only their parental genes but also unrelated genes. Therefore, pseudogenes have emerged as a previously unappreciated class of sophisticated modulators of gene expression, with a multifaceted involvement in the pathogenesis of human cancer.

The paper concludes,

The function of the great fraction of the human genome (98%) composed of sequences that do not encode proteins remains a mystery. Pseudogenes are technically part of this fraction, and the examples described here clearly demonstrate that they perform a broad and multifaceted spectrum of activities in human cancer. Therefore, the name pseudogenes, which underlies their close sequence similarity with parental counter-parts, should not imply a negative connotation. They might be “pseudo” genes because they do not encode a protein or because they encode a protein that does not function in the same way as that encoded by their cognate genes. Nonetheless, they are functionally disabled but can perform different functions than their parental gene counterparts.

The overall paper contains a lot of fascinating material and extensive references. I hope to review this material in more detail shortly. In the meantime, you can download the full paper here!

Jerad, Does the paper say the pseudogenes, when properly functioning, cause cancer, or does it say that defects/mutations in the pseudogenes can lead to cancer? The latter is essentially always the case when we hear announcements in the news that scientists have discovered the 'gene' for such-and-such disease. Eric Anderson
Jerad Conversely, if its function is i>per simpliciter to make it easier to kill the host, doesn't that also make it easier to be selected out pronto? The idea of pseudogenes is that they're harmless enough to hang around being useless indefinitely. But cancer is both common and harmful. Jon Garvey
Eric, It's ironic 'cause ENCODE was studying the genome the way it is NOW and saying 80% of it has 'function'. And it would be ironic if part of the 'function' is to make it easier to kill the host. AND not a good adaptation really. What kind of advantage does that give to the host? I've got an answer for that (I think) 'cause it's stupid to ask questions you haven't thought hard about the answers to. Jerad
What's ironic? Both studies underscore the fact that the genome is more pervasively functional than suggested by traditional evolutionary theory and that concepts like 'junk DNA' and 'pseudogenes' are ignorance-of-the-gaps concepts that retard scientific understanding rather than contributing to it. Eric Anderson
gpuccio (2): I was kidding. But the story is kind of ironic after the ENCODE press release. Jerad
Jerad: Maybe you are just joking, but just to clarify: the genes have useful functions; when those functions are altered, cancer can ensue. That just proves how important the original function is. It's the same for the so called "oncogenes", furst discovered for their role in cancer, and then recognized as fundamental regulatory transcription factors, involved in cell cycle regulation. gpuccio
Oh great, part of the 'function' of the genome is to kill us! hahahahahahah That's good design eh? :-) Built in self-destruct. Jerad

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