De-Novo Gene Origination from protogenes.

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Re: De-Novo Gene Origination from protogenes.

#61  Postby Rumraket » Feb 28, 2017 5:32 pm

Calilasseia wrote:What I'd like to know, is why a gene purportedly not associated with a peptide product, in the case of CLLU1, is being used as a diagnostic marker for chronic lymphocytic leukaemia? Without a gene product to test for, it's difficult to imagine how this gene can be detectably up-regulated in individuals with the disease.

Many genes are RNA genes, they produce transcripts that yield functional RNAs. They never go on to be translated into protein, but they are functional even in their RNA form.

For example, RNA regulatory elements are quite common. They have sequences that bind to known protein-coding genes and inhibit transcription. It is estimated the human genome has over 10.000 functional RNA coding genes.

http://sandwalk.blogspot.dk/2011/05/whats-in-your-genome.html

The case for junk DNA:
http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004351

On junk and functional non-coding RNA:
https://www.ncbi.nlm.nih.gov/pubmed/25674102
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Re: De-Novo Gene Origination from protogenes.

#62  Postby Calilasseia » Feb 28, 2017 5:59 pm

Rumraket wrote:
Calilasseia wrote:What I'd like to know, is why a gene purportedly not associated with a peptide product, in the case of CLLU1, is being used as a diagnostic marker for chronic lymphocytic leukaemia? Without a gene product to test for, it's difficult to imagine how this gene can be detectably up-regulated in individuals with the disease.

Many genes are RNA genes, they produce transcripts that yield functional RNAs. They never go on to be translated into protein, but they are functional even in their RNA form.

For example, RNA regulatory elements are quite common. They have sequences that bind to known protein-coding genes and inhibit transcription. It is estimated the human genome has over 10.000 functional RNA coding genes.

http://sandwalk.blogspot.dk/2011/05/whats-in-your-genome.html

The case for junk DNA:
http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004351

On junk and functional non-coding RNA:
https://www.ncbi.nlm.nih.gov/pubmed/25674102


Got it. Another gap in my pre-meal knowledge filled ... I should remember to eat before posting, so that I have enough blood sugar to think clearly. :)

However, if this gene is producing an RNA regulatory element that wasn't being produced previously, then it still counts as a de novo gene. If a DNA sequence that previously exhibited no detectable activity, and whose homologues in other organisms are likewise inactive, starts exhibiting activity not previously found, and said activity is of the same sort as other, well-defined genes, then that sequence is a de novo gene by definition.
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Re: De-Novo Gene Origination from protogenes.

#63  Postby Rumraket » Feb 28, 2017 6:00 pm

Calilasseia wrote:
Rumraket wrote:
Calilasseia wrote:What I'd like to know, is why a gene purportedly not associated with a peptide product, in the case of CLLU1, is being used as a diagnostic marker for chronic lymphocytic leukaemia? Without a gene product to test for, it's difficult to imagine how this gene can be detectably up-regulated in individuals with the disease.

Many genes are RNA genes, they produce transcripts that yield functional RNAs. They never go on to be translated into protein, but they are functional even in their RNA form.

For example, RNA regulatory elements are quite common. They have sequences that bind to known protein-coding genes and inhibit transcription. It is estimated the human genome has over 10.000 functional RNA coding genes.

http://sandwalk.blogspot.dk/2011/05/whats-in-your-genome.html

The case for junk DNA:
http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004351

On junk and functional non-coding RNA:
https://www.ncbi.nlm.nih.gov/pubmed/25674102


Got it. Another gap in my pre-meal knowledge filled ... I should remember to eat before posting, so that I have enough blood sugar to think clearly. :)

However, if this gene is producing an RNA regulatory element that wasn't being produced previously, then it still counts as a de novo gene. If a DNA sequence that previously exhibited no detectable activity, and whose homologues in other organisms are likewise inactive, starts exhibiting activity not previously found, and said activity is of the same sort as other, well-defined genes, then that sequence is a de novo gene by definition.

Yep, I would agree.
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Re: De-Novo Gene Origination from protogenes.

#64  Postby Wortfish » Mar 01, 2017 2:03 am

Calilasseia wrote:
Got it. Another gap in my pre-meal knowledge filled ... I should remember to eat before posting, so that I have enough blood sugar to think clearly. :)


Some RNAs can act as catalysts (like enzymes) and so are called "ribozymes". They are a key component of the RNA World hypothesis.

However, if this gene is producing an RNA regulatory element that wasn't being produced previously, then it still counts as a de novo gene. If a DNA sequence that previously exhibited no detectable activity, and whose homologues in other organisms are likewise inactive, starts exhibiting activity not previously found, and said activity is of the same sort as other, well-defined genes, then that sequence is a de novo gene by definition.


Knowles and Mclysaght claimed that CLLU1 is protein-coding in humans but not in other primate lineages because there is a valid ORF in the former. That is what they mean by de novo. The NCBI refutes this claim, stating that it is actually a ncRNA gene that is present in humans and other primates. As such, there is nothing de novo about it at all.
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Re: De-Novo Gene Origination from protogenes.

#65  Postby Rumraket » Mar 01, 2017 10:23 pm

Wortfish wrote:Knowles and Mclysaght claimed that CLLU1 is protein-coding in humans but not in other primate lineages because there is a valid ORF in the former. That is what they mean by de novo. The NCBI refutes this claim, stating that it is actually a ncRNA gene that is present in humans and other primates. As such, there is nothing de novo about it at all.

True if, in fact, it is functionally transcribed in both humans and other primates. But we don't know that, or at least, noone has shown whether it is transcribed at a significant level in anything but humans. Orthologous sequences exist in our primate cousins, but whether they are similar enough to other transcription factor binding sites in those primate genomes, in order to recruit transcription factors and get expressed at selectively/physiologically significant levels, remains to be seen.

Of course, lacking an open reading frame, it will not constitute a de novo protein coding gene. It might still constitute a de novo ncRNA. But to settle that we need transcription data from other primates.
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Re: De-Novo Gene Origination from protogenes.

#66  Postby Wortfish » Mar 05, 2017 2:46 pm

Rumraket wrote:
Of course, lacking an open reading frame, it will not constitute a de novo protein coding gene. It might still constitute a de novo ncRNA. But to settle that we need transcription data from other primates.


We do have expression data from other primates. But we haven't characterized the structure and function of the ncRNA transcript.
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Re: De-Novo Gene Origination from protogenes.

#67  Postby Rumraket » Mar 05, 2017 2:48 pm

Wortfish wrote:
Rumraket wrote:
Of course, lacking an open reading frame, it will not constitute a de novo protein coding gene. It might still constitute a de novo ncRNA. But to settle that we need transcription data from other primates.


We do have expression data from other primates.

Please provide it.
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Re: De-Novo Gene Origination from protogenes.

#68  Postby mingthething » Mar 30, 2017 8:33 am

Animavore wrote:Why's this in 'creationism'.


Because one claim that keeps cropping up is you 'can't create new information' .
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Re: De-Novo Gene Origination from protogenes.

#69  Postby Calilasseia » Mar 30, 2017 12:07 pm

mingthething wrote:
Animavore wrote:Why's this in 'creationism'.


Because one claim that keeps cropping up is you 'can't create new information' .


An assertion that is known to be bullshit by anyone who actually paid attention in a real information theory class.
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Re: De-Novo Gene Origination from protogenes.

#70  Postby Wortfish » Apr 14, 2019 11:53 pm

This paper claims AFGP generation from a non-coding sequence in gadids. Molecular mechanism and history of non-sense to sense evolution of antifreeze glycoprotein gene in northern gadids: https://www.pnas.org/content/116/10/4400

As far as I can tell, the proposed sequence of events is just wishful thinking and absurd speculation by the authors:

Image

Evolutionary mechanism of the gadid AFGP gene from noncoding DNA. The color codes of the sequence components follow Fig. 1. (A) The ancestral noncoding DNA contained latent signal peptide-coding exons with a 5′ Kozak motif, adjacent to a duplication-prone 27-nt GCA-rich sequence. (B) The 27-nt GCA(Ala)-rich sequence duplicated forming four tandem copies. (C) A 9-nt in the midst of the four 27-nt duplicates became the three codons for one AFGP Thr-Ala-Ala unit and underwent microsatellitelike duplication forming a proto-ORF. (D) A proximal upstream regulatory region acquired through a putative translocation event. (E) A 1-nt frameshift led to a contiguous SP, a propeptide, and a Thr-Ala-Ala-like cds in a read-through ORF. (F) Intragenic (Thr-Ala-Ala)n cds amplification, fulfilling the antifreeze function under natural selection.
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Re: De-Novo Gene Origination from protogenes.

#71  Postby Rumraket » Apr 15, 2019 12:06 am

Then your "telling" is not very far indeed.
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Re: De-Novo Gene Origination from protogenes.

#72  Postby Wortfish » Apr 15, 2019 12:25 am

Rumraket wrote:Then your "telling" is not very far indeed.


Well, there is a heck of a lot of neutral evolution proposed in the paper. However, the authors dishonesly try to pass it off as selection.
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Re: De-Novo Gene Origination from protogenes.

#73  Postby Spearthrower » Apr 15, 2019 12:30 am

Wortfish wrote:
Well, there is a heck of a lot of neutral evolution proposed in the paper.


They're not mutually exclusive.


Wortfish wrote:However, the authors dishonesly try to pass it off as selection.


Rather rude of you to call it dishonest, isn't it? Especially when you're clearly lacking sufficient knowledge to understand that neutral evolution and selection can both be operating simultaneously.

Have you been going through their dustbins? What's your angle on calling the authors dishonest? I want to know.
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Re: De-Novo Gene Origination from protogenes.

#74  Postby Wortfish » Apr 15, 2019 2:39 am

Spearthrower wrote:
Wortfish wrote:
Well, there is a heck of a lot of neutral evolution proposed in the paper.


They're not mutually exclusive.


Wortfish wrote:However, the authors dishonesly try to pass it off as selection.


Rather rude of you to call it dishonest, isn't it? Especially when you're clearly lacking sufficient knowledge to understand that neutral evolution and selection can both be operating simultaneously.

Have you been going through their dustbins? What's your angle on calling the authors dishonest? I want to know.


IF you care to read the paper, the authors claim that a stretch of ncDNA came under selective pressure BEFORE the regions was even transcribed:

"We hypothesize that, upon the onset of selective pressure from cold polar marine conditions, duplications of a 9-nt ancestral element in the midst of the four GCA-rich duplicates occurred. As the number of AFGP tripeptide-coding repeats increased, the antifreeze function would become augmented."


This is stage B. Only at stage D (see the figure in the post above) did the "proto-gene" acquire transcriptional ability. So, the authors are claiming that selection was involved in the formation of the gene when it could not have been.
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Re: De-Novo Gene Origination from protogenes.

#75  Postby Spearthrower » Apr 15, 2019 2:59 am

Wortfish wrote:
IF you care to read the paper, the authors claim that a stretch of ncDNA came under selective pressure BEFORE the regions was even transcribed:


It clearly says before the regulatory element to activate transcription was acquired.

The gadid AFGP evolutionary process also represents a rare example of the proto-ORF model of de novo gene birth where a fully formed ORF existed before the regulatory element to activate transcription was acquired.


Wortfish wrote:
"We hypothesize that, upon the onset of selective pressure from cold polar marine conditions, duplications of a 9-nt ancestral element in the midst of the four GCA-rich duplicates occurred. As the number of AFGP tripeptide-coding repeats increased, the antifreeze function would become augmented."


This is stage B. Only at stage D (see the figure in the post above) did the "proto-gene" acquire transcriptional ability. So, the authors are claiming that selection was involved in the formation of the gene when it could not have been.


That's clearly not what it says. You've misread it. You should make sure you understand what you are saying before accusing others of dishonesty lest people levy the same charge against you.
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Re: De-Novo Gene Origination from protogenes.

#76  Postby Rumraket » Apr 15, 2019 11:21 am

Wortfish wrote:IF you care to read the paper, the authors claim that a stretch of ncDNA came under selective pressure BEFORE the regions was even transcribed:

"We hypothesize that, upon the onset of selective pressure from cold polar marine conditions, duplications of a 9-nt ancestral element in the midst of the four GCA-rich duplicates occurred. As the number of AFGP tripeptide-coding repeats increased, the antifreeze function would become augmented."


This is stage B. Only at stage D (see the figure in the post above) did the "proto-gene" acquire transcriptional ability. So, the authors are claiming that selection was involved in the formation of the gene when it could not have been.

I would agree that it's a badly worded sentence. What they mean is that additional duplications of the tripeptide repeat also happened after the proto-ORF had ackquired transcriptional regulation. That's why the dark blue part in the figure become significantly longer in the last step F, as they write in the figure legend: "(F) Intragenic (Thr-Ala-Ala)n cds amplification, fulfilling the antifreeze function under natural selection."
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Re: De-Novo Gene Origination from protogenes.

#77  Postby Wortfish » Apr 15, 2019 11:20 pm

Rumraket wrote:
I would agree that it's a badly worded sentence. What they mean is that additional duplications of the tripeptide repeat also happened after the proto-ORF had ackquired transcriptional regulation. That's why the dark blue part in the figure become significantly longer in the last step F, as they write in the figure legend: "(F) Intragenic (Thr-Ala-Ala)n cds amplification, fulfilling the antifreeze function under natural selection."


Actually, there were 3 duplication events claimed by the authors. Look again at the figure.

(B) The 27-nt GCA(Ala)-rich sequence duplicated forming four tandem copies.
(C) A 9-nt in the midst of the four 27-nt duplicates became the three codons for one AFGP Thr-Ala-Ala unit and underwent microsatellitelike duplication forming a proto-ORF.
(D) A proximal upstream regulatory region acquired through a putative translocation event.
(E) A 1-nt frameshift led to a contiguous SP, a propeptide, and a Thr-Ala-Ala-like cds in a read-through ORF.
(F) Intragenic (Thr-Ala-Ala)n cds amplification, fulfilling the antifreeze function under natural selection.

Only the last part could have been selected for because transcriptional activity was present. Prior to this, there was no promoter to transcribe the sequence let alone translate it. Stage B and Stage C (the one I referred to involving the repeats of the 9nt element).
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Re: De-Novo Gene Origination from protogenes.

#78  Postby Wortfish » Apr 15, 2019 11:36 pm

Spearthrower wrote:
Wortfish wrote:
IF you care to read the paper, the authors claim that a stretch of ncDNA came under selective pressure BEFORE the regions was even transcribed:


It clearly says before the regulatory element to activate transcription was acquired.


AFTER the initial duplications of the sequence. This means that these duplications would not have been subject to any selective pressure.
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Re: De-Novo Gene Origination from protogenes.

#79  Postby Rumraket » Apr 16, 2019 12:24 pm

Wortfish wrote:
Rumraket wrote:
I would agree that it's a badly worded sentence. What they mean is that additional duplications of the tripeptide repeat also happened after the proto-ORF had ackquired transcriptional regulation. That's why the dark blue part in the figure become significantly longer in the last step F, as they write in the figure legend: "(F) Intragenic (Thr-Ala-Ala)n cds amplification, fulfilling the antifreeze function under natural selection."


Actually, there were 3 duplication events claimed by the authors. Look again at the figure.

Yes, and the one under selection is the last one. Obviously.
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Re: De-Novo Gene Origination from protogenes.

#80  Postby Wortfish » Apr 16, 2019 2:15 pm

Rumraket wrote:
Wortfish wrote:
Rumraket wrote:
I would agree that it's a badly worded sentence. What they mean is that additional duplications of the tripeptide repeat also happened after the proto-ORF had ackquired transcriptional regulation. That's why the dark blue part in the figure become significantly longer in the last step F, as they write in the figure legend: "(F) Intragenic (Thr-Ala-Ala)n cds amplification, fulfilling the antifreeze function under natural selection."


Actually, there were 3 duplication events claimed by the authors. Look again at the figure.

Yes, and the one under selection is the last one. Obviously.


The duplication event I am referring to is step C which precedes Step D (the gain of the promoter):

We hypothesize that, upon the onset of selective pressure from cold polar marine conditions, duplications of a 9-nt ancestral element in the midst of the four GCA-rich duplicates occurred. As the number of AFGP tripeptide-coding repeats increased, the antifreeze function would become augmented.
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