The August, 2006 Scientific American article entitled The Real Life of Pseudogenes discussed the fact that at least almost half (19,000 and maybe more) of the human genome (21,000 functional genes, 40,000 total) consists of "pseudogenes", non-functional genes that do not produce proteins. Most of those are copies (11,000) of actual functioning genes elsewhere in the genome, the rest (8,000) have no counterpart in the genome. The overall distribution of pseudogenes in the human genome appears to be random, although some local genome regions tend to contain more pseudogenes.

Interesting tidbits of information are being derived from these pseudogenes.

For example, in mice and rodents and most other mammals, the gene sequence for making Vitamin C (so the mice don't have to eat citrus or other sources of Vitamin C) is as follows: CHRNA2-EPHX2-GULO-CLU-SCARA3

In primates, incluidng humans, the gene sequence is as follows: CHRNA2-EPHX2-'P'GULO-CLU-SCARA3 ; where the 'P' indicates GULO is a non-functioning pseudogene, having almost idential encoding as the real gene, but with some errors that make it non-functional.

As a consequence, primates require an external source of Vitamin C to avoid scurvy.

Evolutionary theory posits that at some time in the past circa 40 million years ago, primate ancestors lived in an environment rich in Vitamin C, and loss of the ability to make one's own Vitamin C incurred no net detriment to the animals, so random errors on that gene making it a non-functional gene would eventually lead to all progeny having those errors, and the gene being non-functional, without any dire consequences. The same thing happens to fish or other animals that become locked in caves with no light - they lose their ability to see, with no adverse consequence to the organism.

Pseudogenes are created by several different methods. Insertion of a premature stop codon; a gross deletion of nucleotide (A,C,G,T) bases, or non-synonomous mutation (change in nucleotide)

So the question for the IDists out there is - WHY would people and the other primates be created with a pseudogene for making Vitamin C, which is currently non-functional, exactly analogous to that for the other non-primate mammals, in which it is functional.

Personally, I found that article to be one of the most interesting articles in the biological sciences ever published by Scientific American. The study of pseudogenes is apparently in its infancy, and much information about our, and every other living organism's evolutionary past should emerge.

I'll have to read the article tomorrow. I've never heard of the term "pseudogenes." Most of what we call "junk DNA" are now being found to be associated with protein synthesis by linkage.

Actually pseudogenes are a common term describing inactive gene sequences. Most of them are probably derived from mutated genes. Slightly more is known regarding pseudogenes in prokaryotes as due to the extensive horizontal gene transfers complete genes are inserted which are then not stably inherited (e.g. because they do not confer any selective advantages) and then in a first step of become pseudogenes and eventually might get lost again.
Other common sources for pseudogenes are transpositions events as well as (other) gene duplications (e.g. due to recombination events) resulting in multiple copies of a certain gene. Just to add some random info here.

Junk DNA on the other hand are something completely different. Most of them are intergenic gene regions which are now more and more found to be associated with gene regulation.

That sounds like an interesting article Walter. Thank you for drawing it to our attention.

I also liked the question you derived from it for the IDiots. It is telling that so far none of them have responded. A bit too technical for them, I imagine.

Walter: I still have to read the whole article but in the intro they state: "Pseudogenes may analogously be vestiges of old code associated with defunct routines, but they also constitute a fascinating record contained within the overall program of how it has grown and diversified over time."

I don't think there is any argument here that a great proportion of our genes have been passed down through the ages to us from our ancestors as we evolved. I read a study a few weeks back that shark and lampreys' median and radial fins share 12 genes with human arms and legs.

this is interesting.... thanks for sharing.

-MT

How would a genome ever be able to delete genes in nature, anyway? Maybe "pseudogenes" can only be suppressed, not deleted.

THE FACT that they have been suppressed.... is facinating.

it is amazing to think, i have the genes, to make my own vitamin c, except due the occurance of some dna detail, i am forced to eat fruit.... fascinates me.

what if we could activate all our dorment genes....

-MT

Interesting information about the common genes for shark fins and arms/legs. Ties in to that earlier post of yours, Valich, about the first true legged fish fossils recently found.

Also, the thought occurred that pseudogenes can be used as a genetic clock. For example, the pseudogene in the Vitamin C sequence would have remained the same in the primates (even as it 'evolved' more errors) until a divergece (speciezation) occured, such as the the great apes separating from the others. Thereafter, the great-ape pseduogene would begin taking on its own new errors, at a generally consistent rate over time. The more new errors incorporated, the further back in time would have been the divergence. This could be done for many different pseudogenes common to many related species, to determine their order of divergence!

The errors would occur rather randomly, and consistently, because the evolutionary pressure to eliminate errors is removed. The article itself details that characteristic somewhat.

evolution... seems to be based on circumstance........

interisting.........

-MT

How would a genome ever be able to delete genes in nature, anyway? Maybe "pseudogenes" can only be suppressed, not deleted.

Deletion events are not that uncommon. They can be results of illegitmate recombinations or faulty replication events for instance. Pseudogenes were functional genes once and as I assume that in higher eukaryotes there is not as high a selective pressure for maintaining a small genome those not confering any fitness advantages are not as stringently selected against as for instance in protists.

BTW pseudogenes are not functional and not necessarily only suppressed. Suppression implies a regulatory factor, for instance the lack of a suitable promoter. However pseudogenes might also exhibit massive deletions or any other form of mutation that renders them inactive.

However pseudogenes might also exhibit massive deletions or any other form of mutation that renders them inactive.Misprints in the book of life.

The article also had instances in which pseudogenes can become working genes again (by an appropriate mutation), and re-incorporated into the functioning genome of the organism. It is probable that pseudogenes are part of the panoply of modalities of evolution.

Also, it is believed that the pseudogenes that are essentially duplicates of functioning genes, but with the errors that make them non-functional ("dead", as referenced in the article) arose when the functioning gene was not only duplicated during meiosis, but also an extra copy was erroneously inserted elsewhere in the genome. That extra copy would have provided no net benefit to the organism, and subsequent random mutations would have made it into a pseudogene, conferring no net detriment either (or, at least not in the eukaryontes, as noted by CharonZ the mere fact of having lots of unnecessary DNA in a pro-karyote does have a detriment effect, because the cells are so small and the DNA replicatory mechanism so much more reduced).

Also, on a similar vein, page 32 of August, 2006 Scientific American also has an interesting note that centrosomes have recently been discovered in surf clam eggs which appear to posses their own genetic machinery, though based on RNA, not DNA!
It will be intersting to learn whether they might also possess pseudogenes that are RNA pseudogenes! This is reportedly online via the Proceedings of the National Academy of Sciences USA.

In reading this article, it is not correct to say that the genes "die" or that "mutations cause them to die." The genes are still there, either as relics of the past or as mutations (deletions and insertions). The coding machinerey through mRNA often corrects errors in the genetic code, and future mutations could cause additional insertions that would enable these socalled "pseudogenes" to then code for something else, causing a phenotype mutation. So, as you can see, they're never really dead.

Although we have sequenced the entire human genome, and the genomes of about 50 other species of animals, the real task is to find out what they express for. We don't know how all the amino acids are put together to form the quaternary protein structures and how the proteins then combine to do what. If we knew this, then we would be able to find genetic markers and have tests for all inheritable diseases and possible cures. This is where the major research is at today, and the challenges in genetics. We have to find out the gene expression of the genotype to know the phenotype that it codes for, and this is the basis of biotechnology and gene vector therapy.

Isn't it somewhat presumptuous for someone who'd never heard of pseudogenes previously to now purport to correct the author of the article when he refers to pseudogenes as "dead" genes, to indicate that they no longer are functional, even though still present? If that's the term of art the authors chose, I have no qualms with using it. Clearly the author indicated that they are still present, and that they could become re-activated again in the future, should the proper mutations be included in the future.

Relating to the RNA centrosomes, there seems to be a bit of a mystery behind the functioning of the "microtubular organizing center" (sometimes - not always - referred to as the centrosome) that produces and organizes the microtubule spindles during mitosis. As far as I know, and from what I've been reading in the literature, we really have no idea as to how the microtubular organizing system works. All we know, unless there's new research out now, is that the centrioles inside the microtubular organizing center are thought to somehow help organize the microtubules.

I'm not going to quibble about what terms the author cares to use, but the point was that how can something be dead if it can be reactivated, or come back to life. I think it's a poor choice of wording because it's misleading, but that's a philosophical argument, so let's stick to the subject.

Actually, the author then goes on to correct himself by saying "pseudogenes, and their potential resurrection, suggests some are not entirely dead after all." He seems to want to correct any suggestion in other previous literature that refers to pseudogenes as being dead, and he is correct to do so. He then states that: "Pseudogenes are born in two ways:" extra copy during cell duplication, or reverse transcription > retrotransposition.

These are the best diagrams I've ever seen that clearly describe coding transcription and reverse transcription.

Pseudogenes are relics of our evolution passed down from ancestrial species. I did a recent study on "The Canine Genome and How it Can Help Find and Cure Inheritable Diseases in Both Dogs and Humans" due to the 77% similarity between their genomes. I found one gene on a genetic sequence nucleotide divergence map of the dog's chromosome on chromosome 13 at LOC475061 that codes for mRNA [similar to H+-exporting ATPase (EC 3.6.3.6) chain C, vacuolar] that is a homologene (a putative homolog to another gene) from the ancestrial divergent hominid, mice, rats, chickens, fruit flys, viruses, yeast, fungi, fruiting bodies, all the way down to rice. Another one found on chromosome 5 is a homologene to breast cancer. Fascinating!

See: http://www.ncbi.nlm.nih.gov/mapview/map_search.cgi?taxid=9615

Much better!

I think its a really good article. I just had to think about the author's perspective.

Pseudogenes can often be vestial appendeges of evolution, but to take them out can change the 3d composition of dna, which can affect not only splicing of gene, but how other proteins enzymes ect affect each other.

Pseudogenes are genotype mutations (deletions or additions in the nucleotide bases). The only relation that they have to vestial appendages is that they may both be remnants from our ancestrial species, but they are completely different. A vestial appendage is a phenotype formed from a fully intact genotype. Pseudogenes are a genotype code that codes for nothing, until perhaps it matches up with neighboring nucleodite base codes that then could possibly code for some new type of phenotype mutation, but this is highly improbable given the number of amino acids it would have to code for to produce the proteins then the quaternary structure then the mutated phenotype.

Valich,

Your penchant for misunderstanding strikes again.

What she was saying is that pseudogenes are genes that are no longer function. Thus they are analogous to vestigial appendages and/or organs. They serve no purpose.

Her main point was that even though they don't directly serve a purpose, they do shape the chromosome and thus affect the way genes are expressed.

A very interesting point, actually. One which had never occurred to me.

Pseudogenes can often be vestial appendeges of evolution, but to take them out can change the 3d composition of dna, which can affect not only splicing of gene, but how other proteins enzymes ect affect each other.

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M*W: Are you talking about telomerase, for example?