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140 pseudogenes found expressed in humans

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From Nature

A draft map of the human proteome

Extract “In our data set, we identified more than 200 peptides that are encoded by 140 pseudogenes. These 140 pseudogenes originate from 110 parental genes. To derive this unambiguous set, we filtered out several peptides for which sequence change could be explained by SNPs reported for corresponding genes in dbSNP. When we looked at the tissue distribution of the translated pseudogenes, we observed that roughly half of the pseudogenes were translated in a cell/tissue-restricted manner whereas a small minority was expressed globally (Fig. 5a), a
pattern similar to that described for pseudogene transcripts30, 31. For instance, VDAC1P7 was found to be translated globally (22 of 30 cells/tissues analysed) whereas MAGEB6P1 was detected only in adult testes although its parental gene, EIF4B, is widely expressed (Fig. 5a). Extended Data Fig. 5c shows two peptides that map to MAGEB6P1, a pseudogene, along with an alignment of the identified peptides with the corresponding peptides in the parental gene. It should be noted that there is still a small chance that some SNPs are not represented in our analysis because we did not analyse the genomes of these individuals. However, this is unlikely to affect our results greatly because it has been estimated that approximately 98% SNPs with 1% frequency have been detected from the 1000 Genomes Project32.”

Talk about The Myth of Junk DNA.

See also: Junk DNA defender doesn’t do politeness.

Anyoe remember ENCODE? Not much junk DNA? Still not much.

What? Darwin’s followers did not use junk DNA as an argument for their position? Indeed, Christian Darwinists were hollering fer Jesus on the basis of junk DNA not too long ago too. Sorry, but it’s true.

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Comments
Moose Dr: There's also a difference between "not being known to have a function" and "known to not have function". Function is something to be demonstrated and not assumed as the default. If a sequence is not known to have a function, we can hypothesise that it has no function. This hypothesis is falsifiable, because function can be demonstrated. If we try and try again but still can't show that it has a function, its functionlessness becomes more likely. Just to be clear: when we speak of functional sequences, it's the sequence itself that matters, not its bulk, for example (irrespective of what makes it up)Piotr
June 2, 2014
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Piotr (12) "There’s a difference between being “of unknown function” and not being known to have a function." Did you mean:"Of unknown function" is different than "known to not have function?" What percent of DNA is known to not have function? How is this known?Moose Dr
June 2, 2014
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"Junk of the gaps," lol...jstanley01
June 1, 2014
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Dionisio: I don't think that aspect has to do with the "central dogma". It's just that proteins are synthesized in very different quantities. Some of them are produced in all tissues, and in great quantities (the "housekeeping" type). Others are necessary in selected contexts. Those are probably the most interesting in terms of cell differentiation and of procedural information in the genome. It will be interesting, for example, to check in depth the behaviour of transcription factors. When we look at the proteins, the final effectors, we miss much of the intermediate complexity in the transcriptome (especially the nuclear RNA). However, that is an important and interesting approach too, which completes the transcriptomic data.gpuccio
May 30, 2014
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gpuccio
It is interesting, for example, that “The bulk of protein mass is contributed by only a small number of genes. Only 2,350 ‘housekeeping genes’ account for ~75% of proteome mass.”
Perhaps this is a dumb question: How does your quoted comment relate to the so called 'central dogma' of biology, which I studied in the online classes I took not so long ago and read it in a biology textbook? Thanks.Dionisio
May 29, 2014
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However, this is a good start, and it is important to begin with some global quantitative assessment of the expression of good old proteins in different cells.
Yes, the party has just started. The fun part is still ahead. Get ready to celebrate! :)Dionisio
May 29, 2014
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What is the evidence they don’t have function? There's none, all we know is that they exist. I'd be surprised if none of them had been co-opted into some role or other. But you have to consider what the null hypotheses is with regard function, a broken gene can still make a protein after all.wd400
May 29, 2014
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The importance of this map is that t gives us, for the first time, a global idea of differential translation. It is interesting, for example, that "The bulk of protein mass is contributed by only a small number of genes. Only 2,350 ‘housekeeping genes’ account for ~75% of proteome mass." On the other hand, there are 1537 genes detected only in one sample.gpuccio
May 29, 2014
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Mung: I suppose that proteomics is still a little back if compared to transcriptomics, if we look at those 30 cell types against the more than 500 individual transcriptomes in the FANTOM5 paper. However, this is a good start, and it is important to begin with some global quantitative assessment of the expression of good old proteins in different cells.gpuccio
May 29, 2014
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I was referring to the things being detected in the study, which as you say are peptides by anyone's definition (even if the difference between a long peptide and a short protein is pretty arbitrary). With that cleared up, I'll emphasize that mere detection of peptides derived from these pseudogenes doesn't establish the pseudogenes have a biological function.wd400
May 29, 2014
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Wd400
Or the fact that there’s no evidence these peptides actually do something.
What is the evidence they don't have function?Jehu
May 29, 2014
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The products of the pseudo gene are proteins here. I am not getting "hung up" because I work in the field that uses peptides and I can guarantee there is a huge difference when someone says peptide you would never say protein product as a replacement. To understand how this work was performed and proteins identified relies on understanding that difference. Thus to say what you said could confuse people into thinking that these pseudogenes merely are fragments of useful proteins which is unlikely to be true, but rather functional proteins which is a big difference. As such it does need clarification. The peptides talked about in this paper are generated by chopping up the proteins present into peptides to put down a mass spec then mapping those peptides to their respective proteins. The peptides are not functional.Dr JDD
May 29, 2014
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Just looking at the genome from a pure information perspective, it has always been certain that there is more functional DNA than was originally estimated. This observation, however, goes against Darwinian time constraints. For Darwinism, the less specified information organisms contain the more probable is evolution by RM + NS. So we find a presumption amongst Darwinists that any given DNA is "junk" unless proven otherwise.Jehu
May 29, 2014
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Are you getting hung up on some definition peptide? I mean the products of the "pseudogenes".wd400
May 29, 2014
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The point is yes in this case it is a few percent
It's a fraction of one percent, to be more precise.Piotr
May 29, 2014
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I'm not quite sure you understand what these peptides from the study are, wd400. Function of "peptides" is completely irrelevant here.Dr JDD
May 29, 2014
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The link was meant to the database used in this study. That, surely, is the only relevant denominator. I did read the rest of your comment, there may well be a few more "pseudogenes" that make a protein in one or other cell-type (indeed you'd expect this even they are all junk) but the law of diminishing returns means it's unlikely many do, at least an appreciable level.
What peptides?
The peptides deriving from currently-annotated pseudogenes detected in this study.wd400
May 29, 2014
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wd400 I cannot see where your link goes. Doesn't seem to be working. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491395/ had estimate at 14-15,000 based on multiple approaches to estimate.
I’m afriad none of the rest your comments change the fact a very small proportion of the annotated-pseudogenes produce a protein.
No, they don't in this context (i.e. 30 broad tissue types). But if you bothered to read my whole post my point was there is likely more unknown function in more specific subsets (harder to study, unlikely to identify masses of new proteins in well studies major tissue types, common sense deduction), therefore it is possible this is indeed just a fraction of translated pseudogenes. And my other point was it does not detract that many other functions are being attributed to transcribed pseudogenes (that are not translated, thus as RNA). My point is this study just keeps adding bit by bit.
Or the fact that there’s no evidence these peptides actually do something.
What peptides? Piotr @#12 But it isn't just pseudogenes. This is just a fraction of a growing puzzle. Another piece that is slowly building up. Every time another piece is added, say lncRNA, it is "just a few percent" to take away from junk. But then there is something else that is just a few percent, there is ~50% repetitive elements, importantly as this study found, proteins coded from regions not expected to code proteins (apart from pseudogenes). The point is yes in this case it is a few percent but it is all headed in one direction i.e. towards more and more complexity, more and more functionality. Yet all the while, evolution still cannot explain how developmental genes can arise in Cambrian or for that matter be mutated without detrimental effects beyond that and it is supposed to be taken as fact. Most evolutionists would be fantastic groundsmen in stadiums as they are so good at constantly moving the goalposts.
There’s a difference between being “of unknown function” and not being known to have a function.
Are you presuming I do not know that? Clearly your inference is just presuming that. I meant what I said.Dr JDD
May 29, 2014
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When I said "it still isn't much", I meant that all known pseudogenes add up to some 1.2% of the genome (correct me if I'm wrong). Let's say that 20% of them may yield a functional RNA product (that's more than twice as much as predicted in the GENCODE paper): such coopted pseudogenes are not junk, of course, but 0.24% of the genome still "isn't much". Just a fraction of these may potentially be resurrected as protein-coding genes.
I was proposing to my peers that what was described as junk DNA was in fact simply DNA of unknown function
There's a difference between being "of unknown function" and not being known to have a function.Piotr
May 29, 2014
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gpuccio:
Great online resource (from the paper).
Thanks! But only 30 cell types, out of how many? See also: Human Protein Reference Database "The fact that 193 of the proteins came from DNA sequences predicted to be noncoding means that we don't fully understand how cells read DNA, because clearly those sequences do code for proteins." hereMung
May 29, 2014
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Actually its more like 14-15,000.
17,172. In the database they actually used. I'm afriad none of the rest your comments change the fact a very small proportion of the annotated-pseudogenes produce a protein. Or the fact that there's no evidence these peptides actually do something.wd400
May 29, 2014
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Jehu: Indeed, if those genes code for proteins they should be reclassified as protein coding genes. In other cases, the function of pseudogenes was regulatory, and not expressed by the coding of a protein. That would be true non protein coding function.gpuccio
May 29, 2014
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From a list of > 17,000 pseudogenes known from the human genome. 140 make a protein (which isn’t to say they are functional). What are you trying to make from this, exactly?
Actually its more like 14-15,000. But that is not the point. The point is, it is not 140. This study found 140. There are numerous other papers coming out week by week that describe new function for pseudogenes. This is just adding to the list. Furthermore, not all of the novel proteins that were discovered in this study were from pseudogenes, but some came from places in the genome not classically associated with gene areas, apart from pseudogenes. What does that tell you about our annotation of the genome? A more accurate number of actively transcribed pseudogenes is 1200-1400 (9%). That is currently known (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491395/). Furthermore, pseudogenes are being shown to have roles in regulation events where detection of supposed transcription of them may not be obvious or detectable. You may claim a transcript or even a translated protein proves nothing, and could be wasteful but that is merely to support your own naturalistic views. The common sense answer (i.e. the one that holds to the best inferred based on evidence) would be that if the cell transcribes or translates something, it has function. Furthermore, one would do well to realise the limitation of Mass Spec data, and the number of peptides required for a signal above background to be confidental ascertained. It is highly likely even with state-of-the-art machinery that very low level and non-rapidly turned over proteins may be missed in this analysis. Furthermore, this study looked at approximately 30 tissue "types". So it encompassed all the major tissues so it should be representative I hear people say? Well no, because anyone who delves into the world of toxicology for testing in the pharmaceutical industry know that there are these pesky subsets of tissues that are specialised cells that maybe make <1% of that tissue type but have unique expression profiles. They are pesky because if you are testing your drug in vitro against say a kidney cell and it looks clean, it may be very dirty against a unique subset of kidney cells not highly represented in your study to give a signal. You can see in their tissue types, for example in the T-cell compartment they assess CD4+ and CD8+ but there are other sub-types (what about gamma-delta T-cells?). What about crypt cells in the colon? What about melanocytes in the skin, that make up <1% of those cells? It is in fact very likely that certain genes are only transcribed in these very specialised cells (that is why they are so different). Therefore you will miss such events. What they looked at here were pretty much the major players of tissues. Like I said as well, bear in mind subsets included in those tissues are reduced to noise given the amount of material usually needed to generate a reliable signal in mass spec analysis.
It’s been known for decades that some pseudogenes can be transcribed, and sometimes get translated into proteins. What’s so revolutionary here? And, by the way, it still isn’t much.
That is a mixture of the old denialism of "junk DNA has no function" when confronted with function (i.e. "we never said it was functionless" when historical documents show it was said of this, much like pseudogenes historically not even 10-15 years ago were largely being labelled as proof of evolution and evolutionary left over, and still are!) and also showing belief by omission. By saying that they are "sometimes translated into proteins" it seems clear that you still are reluctant to attribute function to those translated products, but by omission leave enough room to say "I never said they were functionless". Its not revolutionary. I do not think people are claiming it is revolutionary (this pseudogene finding). The whole process is pretty impressive and the databases generated from it are astoundingly useful. However, it is another small piece of the ever growing trend of evidence showing more complexity and more functionality to the human genome despite having years of people tell us most of it is junk and useless and waste, and importantly, laugh at the IDist by way of mocking a designer who could design a genome so poorly. What really is the bottom line once again with each one of these findings is that we really understand so little about genomics, certainly too little to confidently claim that things without apparent function in our current understanding must be the graveyards of evolution. But, it is low-hanging fruit to the naturalist facing the IDist. I said it in another thread - 15 years ago I was proposing to my peers that what was described as junk DNA was in fact simply DNA of unknown function - and so like many other IDers of that last 10-15 years who have said similar, slowly and slowly this is becoming more of a realisation. But no, ID cannot make any useful predictions and contributions to science now can it?Dr JDD
May 29, 2014
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Great online resource (from the paper). http://www.humanproteomemap.org/index.phpgpuccio
May 29, 2014
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If it codes for a protein, how is it a psuedogene? Also, on what basis would you say it doesn't have function?Jehu
May 29, 2014
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It's been known for decades that some pseudogenes can be transcribed, and sometimes get translated into proteins. What's so revolutionary here? And, by the way, it still isn't much.Piotr
May 29, 2014
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My pseudo-genes are only pseudo-expressed.Mung
May 29, 2014
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From a list of > 17,000 pseudogenes known from the human genome. 140 make a protein (which isn't to say they are functional). What are you trying to make from this, exactly?wd400
May 29, 2014
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Human Proteome Project Finds 193 Previously Unknown Proteins - 05/28/2014 Excerpt: Striving for the protein equivalent of the Human Genome Project, an international team of researchers has created an initial catalog of the human “proteome,” or all of the proteins in the human body. In total, using 30 different human tissues, the team identified proteins encoded by 17,294 genes, which is about 84 percent of all of the genes in the human genome predicted to encode proteins. In a summary of the effort, to be published today in the journal Nature, the team also reports the identification of 193 novel proteins that came from regions of the genome not predicted to code for proteins, suggesting that the human genome is more complex than previously thought. ,,, “You can think of the human body as a huge library where each protein is a book,” said Akhilesh Pandey, ,,, “The difficulty is that we don’t have a comprehensive catalog that gives us the titles of the available books and where to find them. We think we now have a good first draft of that comprehensive catalog.”,,, The team’s most unexpected finding was that 193 of the proteins they identified could be traced back to these supposedly noncoding regions of DNA. “This was the most exciting part of this study, finding further complexities in the genome,” said Pandey. “The fact that 193 of the proteins came from DNA sequences predicted to be noncoding means that we don’t fully understand how cells read DNA, because clearly those sequences do code for proteins.” Pandey believes that the human proteome is so extensive and complex that researchers’ catalog of it will never be fully complete, but this work provides a solid foundation that others can reliably build upon. http://www.biosciencetechnology.com/news/2014/05/human-proteome-project-finds-193-previously-unknown-proteins?et_cid=3964356&et_rid=653535995&type=cta Human Proteome Mapped - By Anna Azvolinsky | May 28, 2014 Excerpt: Both studies identified evidence to suggest there is translation from DNA regions that were not thought to be translated—including more than 400 translated long, intergenic non-coding RNAs (lincRNAs)—found by the Küster team—and 193 new proteins—uncovered by the Pandey team. http://www.the-scientist.com/?articles.view/articleNo/40083/title/Human-Proteome-Mapped/bornagain77
May 29, 2014
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The availability of human genome sequence has transformed biomedical research over the past decade. However, an equivalent map for the human proteome with direct measurements of proteins and peptides does not exist yet.
The party has just started... the fun part is still ahead ;-) More research results keep coming out. Let's enjoy it!Dionisio
May 29, 2014
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