Promoters

[Resha Caner]

The argument is that the non-random mechanisms are not pronounced enough to account for 99.9% of human and chimp ERV's being at orthologous positions. At best, retroviral insertion preferences will result in independent but orthologous insertions about 1 in every 50,000 insertions. If chimp and human ERV's were independently acquired then we would expect only 1 in 50,000 ERV's to be orthologous, or about 0.002% of the 200,000 ERV's found in each genome. Instead, 99.9+% are at orthologous positions. IOW, what non-random features that retroviruses do have can be safely ignored with respect to the ERV evidence.

So, even though non-random mechanisms do not account for which gene an ERV inserts into, do they affect where in the gene the insertion occurs? For example, do ERVs tend to insert at the promoter, or do they just insert anywhere?

 

[Loudmouth]

So, even though non-random mechanisms do not account for which gene an ERV inserts into, do they affect where in the gene the insertion occurs? For example, do ERVs tend to insert at the promoter, or do they just insert anywhere?

I would think that it is rare for retrovirus to insert into a gene since genes make up about 2% of the genome. Most of the time, they are going to insert outside of a gene.

Some retroviruses do have preferences for gene rich areas, however. This is most likey due to the fact that areas of the genome undergoing transcription are unwound from histones. Exposed DNA may allow for easier insertion for some retroviruses. This paper does a good job of contrasting a few different retroviruses.

"For HIV the frequency of integration in transcription units ranged from 75% to 80%, while the frequency for MLV was 61% and for ASLV was 57%. For comparison, about 45% of the human genome is composed of transcription units (using the Acembly gene definition)."
Retroviral DNA Integration: ASLV, HIV, and MLV Show Distinct Target Site Preferences

You may get excited when you read that HIV inserts into transcription units 80% of the time, but reading on you learn that nearly half of the 3 billion base genome is made up of transcription units.

 

[Resha Caner]

I would think that it is rare for retrovirus to insert into a gene since genes make up about 2% of the genome. Most of the time, they are going to insert outside of a gene.

Some retroviruses do have preferences for gene rich areas, however. This is most likey due to the fact that areas of the genome undergoing transcription are unwound from histones. Exposed DNA may allow for easier insertion for some retroviruses. This paper does a good job of contrasting a few different retroviruses.

"For HIV the frequency of integration in transcription units ranged from 75% to 80%, while the frequency for MLV was 61% and for ASLV was 57%. For comparison, about 45% of the human genome is composed of transcription units (using the Acembly gene definition)."
Retroviral DNA Integration: ASLV, HIV, and MLV Show Distinct Target Site Preferences

You may get excited when you read that HIV inserts into transcription units 80% of the time, but reading on you learn that nearly half of the 3 billion base genome is made up of transcription units.

I guess I need to learn the terms better before I can properly ask my question.

So, if only 2% of the genome consists of genes, what is the difference between a gene and the rest of the genome? Is this a "junk DNA" type thing? If so, I'm not asking about a preference for non-junk vs. junk DNA.

What is a histone and a transcription unit? From the sound of the term, the "transcription unit" may be closer to what I'm asking. From that term it sounds as if there is some means of dividing the genome into units. I'm asking if insertion prefers the start of a unit or if it will insert anywhere in the unit.

Even then, if only 45% of the genome is made up of these units, is the rest of the DNA just a random string of nothing? With no discernible difference between one part and other? Interesting, but basically irrelevant to my question. Again, I'm asking if, by chance, the insertion happened in the usable part of DNA, is the insertion most likely to happen at the start/end of a "unit", or does it still just happen randomly anywhere?

 

[whois]

Again, I'm asking if, by chance, the insertion happened in the usable part of DNA, is the insertion most likely to happen at the start/end of a "unit", or does it still just happen randomly anywhere?

There is no way we can reasonably apply the term "random mutation" to a DNA transfer process that utilizes dedicated surface structures for bringing two cells together, assembles a multi-protein DNA transport pore connecting the cells, and initiates DNA transfer replication at a specific site on plasmid DNA.

 

[Loudmouth]

So, if only 2% of the genome consists of genes, what is the difference between a gene and the rest of the genome? Is this a "junk DNA" type thing? If so, I'm not asking about a preference for non-junk vs. junk DNA.

If we take a phenotype based view of the gene as an allele, then the gene would could include the upstream promoters and binding domains, sequence that affect mRNA editing, etc. You can consider the gene to be more than just the DNA between the start and stop codons for protein translation.

DNA that does not directly code for proteins can still be functional DNA. DNA that does not affect the fitness of the organism in any discernable manner is junk DNA, and I think almost all of that is non-coding DNA. About 90% of the human genome is accumulating mutations at a rate consistent with not having function that impacts fitness.

To further confuse this situtation, scientists like the ENCODE consortium come in and try to redefine what function is. What they tried to do is conflate the terms "functional" and "does something". Those are not the same thing. The trash in your kitchen trash can releases odor molecules into the air. It does something. However, it is still trash. The same for junk DNA. It is DNA that would not affect the fitness of the organism if it were removed just as your kitchen continues to work just fine after you dump the trash.

What is a histone and a transcription unit?

A histone is a protein that has DNA wrapped around it. Think of it like the sticks at a library that they wrap maps or newspapers around. It is a way of physically compacting DNA.

Transcription units are areas with a lot of genes in them. Think of it as the Earth when you fly over in an airplane. The transcriptional units are the towns where there are more lights, with each house being analogous to a gene.

From the sound of the term, the "transcription unit" may be closer to what I'm asking. From that term it sounds as if there is some means of dividing the genome into units. I'm asking if insertion prefers the start of a unit or if it will insert anywhere in the unit.

When MLV does insert into genes, it tends to insert at the beginning of the gene, as shown in Figure 2 of the paper I mentioned before:

Retroviral DNA Integration: ASLV, HIV, and MLV Show Distinct Target Site Preferences

Even then, if only 45% of the genome is made up of these units, is the rest of the DNA just a random string of nothing? With no discernible difference between one part and other?

It is made up of DNA bases where the retrovirus can insert. However, it probably has very little to no function as it relates to fitness.

Interesting, but basically irrelevant to my question. Again, I'm asking if, by chance, the insertion happened in the usable part of DNA, is the insertion most likely to happen at the start/end of a "unit", or does it still just happen randomly anywhere?

With MLV it tends to happen at the beginning of a gene if it does insert into a gene. However, the bulk of insertions happen outside of genes, and there are also tens of thousands of genes. IOW, this mechanism isn't able to create hundreds of thousands of orthologs between chimps and humans.

 

[sfs]

There is no way we can reasonably apply the term "random mutation" to a DNA transfer process that utilizes dedicated surface structures for bringing two cells together, assembles a multi-protein DNA transport pore connecting the cells, and initiates DNA transfer replication at a specific site on plasmid DNA.

It sounds like you're describing bacterial conjugation, something that has nothing to do with retroviral insertion.

 

[lifepsyop]

To further confuse this situtation, scientists like the ENCODE consortium come in and try to redefine what function is. What they tried to do is conflate the terms "functional" and "does something". Those are not the same thing. The trash in your kitchen trash can releases odor molecules into the air. It does something. However, it is still trash.

I love how evolutionists will turn on their own in an instant the second there is a hint that their darwinian religion may be threatened. You really get a feel for the objective, disinterested pursuit of scientific discovery.

The fact is that nobody knows the full extent of the nature of the function of the genome. Molecular biologists are practically falling out of their chairs every day learning amazing unexpected new things about how these structures operate in the organism.

 

[Resha Caner]

If we take a phenotype based view of the gene as an allele, then the gene would could include the upstream promoters and binding domains, sequence that affect mRNA editing, etc. You can consider the gene to be more than just the DNA between the start and stop codons for protein translation.

DNA that does not directly code for proteins can still be functional DNA. DNA that does not affect the fitness of the organism in any discernable manner is junk DNA, and I think almost all of that is non-coding DNA. About 90% of the human genome is accumulating mutations at a rate consistent with not having function that impacts fitness.

Thanks.

A histone is a protein that has DNA wrapped around it. Think of it like the sticks at a library that they wrap maps or newspapers around. It is a way of physically compacting DNA.

Transcription units are areas with a lot of genes in them. Think of it as the Earth when you fly over in an airplane. The transcriptional units are the towns where there are more lights, with each house being analogous to a gene.

Thanks.

When MLV does insert into genes, it tends to insert at the beginning of the gene, as shown in Figure 2 of the paper I mentioned before

Yeah. The paper also states, "Thus, ASLV and HIV do not strongly favor integration at transcription start sites as was seen with MLV." So, it appears the answer to my question would be, "It depends."

With MLV it tends to happen at the beginning of a gene if it does insert into a gene. However, the bulk of insertions happen outside of genes, and there are also tens of thousands of genes. IOW, this mechanism isn't able to create hundreds of thousands of orthologs between chimps and humans.

That's not why I was asking.

Am I correct that a "promoter" is a region of DNA where transcription initiates? I'm just asking if there is an analog for insertion. Is there a "promoter" that initiates insertion - maybe the same promoter as for transcription - maybe different? So, the gene where the insertion happens and whether that would create orthologs is not part of my question.

Regardless, it seems the answer is basically no - or at least no one has found such a thing.

 

[sfs]

I love how evolutionists will turn on their own in an instant the second there is a hint that their darwinian religion may be threatened. You really get a feel for the objective, disinterested pursuit of scientific discovery.

Quick quiz: only one of the ENCODE papers attempted to estimate the fraction of the genome that actually had a function, in the conventional sense, i.e. that mattered to the organism. What was their estimate? Was it very different from Loudmouth's number? (Hint: they're just about the same.)

Where did you get the idea that junk DNA was an expectation of "darwinian religion", anyway? Strict Darwinists would expect -- and did expect, in fact -- quite the opposite. They expected nearly the entire genome to be functional, since junk DNA is not something natural selection should favor. Nor is completely functional DNA a prediction of creationism, since that view has no problem accommodating all kinds of nonfunctional stuff in the created universe.

This entire line of argument is wrong scientifically, wrong historically, wrong logically and serves here only as an excuse for character assassination.

The fact is that nobody knows the full extent of the nature of the function of the genome. Molecular biologists are practically falling out of their chairs every day learning amazing unexpected new things about how these structures operate in the organism.

Certainly true. It's also true that the same scientists are convinced by the evidence that most of the human genome does not affect the organism's well-being. It's kind of neat the way you flip-flop between treating scientists as discoverers of the truths of nature and treating them as lying toads.

 

[lifepsyop]

Quick quiz: only one of the ENCODE papers attempted to estimate the fraction of the genome that actually had a function, in the conventional sense, i.e. that mattered to the organism. What was their estimate? Was it very different from Loudmouth's number? (Hint: they're just about the same.)

I don't know what paper you're referring to. I'm going by general statements I've read from the research.


Our results demonstrate that regulatory variation is pervasive throughout the genome, on average mildly deleterious, and individuals likely harbor more functionally important variants in noncoding compared with protein-coding DNA.

Personal and population genomics of human regulatory variation


At the outset of ENCODE in 2003, it was widely assumed that evolutionary conservation would prove to be the ultimate arbiter of functional elements in the human genome sequence—all that was lacking was a sufficiently deep sampling of vertebrate genomes for comparative analysis. Correspondingly, highly conserved noncoding sequences were frequently equated with regulatory DNA. For a variety of reasons, both of these expectations missed the mark widely.

The ENCODE Pilot Project raised a general alarm: Most elements defined by biochemical signatures lacked strong evolutionary conservation . Conversely, most highly conserved elements escaped annotation using biochemical or other functional assays ...

Together, these observations suggest that the genome may, in fact, be extensively multiply encoded—i.e., that the same DNA element gives rise to different activities in different cell types. This possibility challenges our current notions of annotation, which are still rooted in a linear world, and cautions against formulating definitions of completeness based on older models such as the delineation of protein-coding genes.

What does our genome encode?

Where did you get the idea that junk DNA was an expectation of "darwinian religion", anyway? Strict Darwinists would expect -- and did expect, in fact -- quite the opposite. They expected nearly the entire genome to be functional, since junk DNA is not something natural selection should favor.

If it turns out that a substantial portion of that "junk" is functionally important to development of the organism then it presents the church of Darwinian mysticism with a major problem. It will suddenly be the case that different types of animals are far, far more dissimilar than previously assumed (as genetic similarity up to this point has been primitively based on only a tiny fraction of protein coding genes)... and along these same lines is the problem of how that much beneficial genomic diversity was selected for in the allotted evolutionary timespans. (i.e. Haldane's Dilemma on steroids.)

This is why the Darwin mystics form such a tight protection circle around certain models of evolution and will not hesitate to go after potential heretics.

Certainly true. It's also true that the same scientists are convinced by the evidence that most of the human genome does not affect the organism's well-being.

That's a distraction. Disabling a genomic region does not have to be deleterious in order to establish obviously meaningful function in relation to the organism. Look at redundancy in engineering for a direct analogy.

It's kind of neat the way you flip-flop between treating scientists as discoverers of the truths of nature and treating them as lying toads.

They are free to discover whatever they wish as long as they do not utter a whisper of dissent against the religion of evolution.

 

[whois]

Quick quiz: only one of the ENCODE papers attempted to estimate the fraction of the genome that actually had a function, in the conventional sense, i.e. that mattered to the organism. What was their estimate? Was it very different from Loudmouth's number? (Hint: they're just about the same.)

i believe there are pros and cons to every issue, this is no different.
the full story cannot be had by reviewing one paper.

This entire line of argument is wrong scientifically, wrong historically, wrong logically and serves here only as an excuse for character assassination.

this happens more often than you might think, from all sides.

It's kind of neat the way you flip-flop between treating scientists as discoverers of the truths of nature and treating them as lying toads.

there are 2 major causes of this.
disinformation and the nature of science.
it's almost impossible for the layman to get the actual story.

 

[whois]

It sounds like you're describing bacterial conjugation, something that has nothing to do with retroviral insertion.

oops, my bad.
it brings up an interesting dilemma though.
if this sort of thing happens with bacteria, then why haven't they evolved, or more appropriately "macroevolved"?

 

[crjmurray]

i believe there are pros and cons to every issue, this is no different.
the full story cannot be had by reviewing one paper.
this happens more often than you might think, from all sides.
there are 2 major causes of this.
disinformation and the nature of science.
it's almost impossible for the layman to get the actual story.

Don't blame your misunderstanding on science. Everyone else seems to learn just fine.

 

[ChetSinger]

Don't blame your misunderstanding on science. Everyone else seems to learn just fine.

I'm afraid I'll have to disagree with that. I think science is hard, and understanding any discipline in depth requires graduate-level education or experience.

 

[crjmurray]

I'm afraid I'll have to disagree with that. I think science is hard, and understanding any discipline in depth requires graduate-level education or experience.

Some people understand science just fine with a highschool education. Some have no understanding after obtaining a college degree.

My point was that you can't blame a lack of understanding of science on some shadowy attempt to keep people uninformed.

 

[lifepsyop]

Some people understand science just fine with a highschool education. Some have no understanding after obtaining a college degree.

In my experience, the most outspoken champions of "science" tend to be the ones most likely to be using the label as a disguise for their own mystical and philosophical worldviews.

 

[crjmurray]

In my experience, the most outspoken champions of "science" tend to be the ones most likely to be using the label as a disguise for their own mystical and philosophical worldviews.

I bet.

 

[PsychoSarah]

oops, my bad.
it brings up an interesting dilemma though.
if this sort of thing happens with bacteria, then why haven't they evolved, or more appropriately "macroevolved"?

They have.

 

[Loudmouth]

Am I correct that a "promoter" is a region of DNA where transcription initiates?

Promoters are where the RNA polymerases sit down on the DNA strand. Transcription of RNA starts downstream of the promoter, and it includes the transcription of a ribosome binding site (RBS). That is where the ribosome sits down on the mRNA, and translation starts at the ATG downstream of the RBS.

I'm just asking if there is an analog for insertion. Is there a "promoter" that initiates insertion - maybe the same promoter as for transcription - maybe different?

From my understanding, RNA polymerases are much more specific than viral integrases. Therefore, viral insertion occurs all over the genome while RNA polymerases only bind to certain portions of the genome.

 

[Loudmouth]

In my experience, the most outspoken champions of "science" tend to be the ones most likely to be using the label as a disguise for their own mystical and philosophical worldviews.

In my experience, you have a serious case of projection.