The Human Genome Is Still Mostly Junk

[Thermos aquaticus]

Interesting stuff...

Hidden Treasures in Junk DNA

It seems the term "Junk DNA" should be expunged from the lexicon.

For what reason? The reason is important. For example:

" But there are other types of proteins called transcription factors, and they have specific interactions with DNA. A transcription factor will bind only at 1,000 places, or maybe the biggest bind is at 50,000 specific places across the genome. And so, when we talk about this 9 percent, we’re really talking about these very specific transcription-factor-to-DNA contacts."

That is a description of DNA doing something. Doing something and function are two different things. We don't say that a promoter of a gene is functional simply because it binds a transcription factor. We say that a promoter of a gene is functional because the RNA or protein that results from the process is important to the fitness of the organism. Junk DNA will bind transcription factors, and it is still junk.

 

[sealchan]

It seems to me that in a complex, adaptive system there is no such thing as junk...at least we may usefully distinguish the isolated significance of certain aspects of a system as having a functional significance with respect to other aspects of connected systems (genes which code functional attributes in the "final product") but the relative "chaos" of the "junk DNA" probably serves a purpose in another context or in the background.

For instance, what if "junk DNA" or non-functional DNA serves as a proving ground for viable mutations such that it increases the likelihood that an organism can produce new, adaptative offspring under rapidly changing environments? Or what if "junk DNA" through regulatory interactions facilitates an adaptative response by leveraging mutations which are influenced by environmental factors in offspring? The process of evolution might have selected for such provisionally influenced adaptations that might help to explain any gaps in the speed of evolution when rapid environment changes occur.

 

[Thermos aquaticus]

It seems to me that in a complex, adaptive system there is no such thing as junk...

If we move from genetics to organismal biology you can see similar features. For example, there are tons of examples of vestigial features, such as the tailbone in humans, toenails on manatees, or a dog's dew claw. If a feature is useless but isn't posing too much of a problem then it is mainly ignored by evolution. Mutations will randomly change the feature, usually shrinking vestigial features over time, as long as those mutations do not increase the very small burden the vestigial organ puts on the organism. The same applies to junk DNA.

The energy needed to produce the ~2.7 billion bases of junk DNA is very, very small compare to the overall energy requirements of the organism. Evolving a system to detect and rid the genome of junk DNA simply doesn't have enough selective pressure pushing on it so that it could evolve. In the end, that is the really hard step in ridding the genome of junk DNA, having a system that can accurately and specifically determine which parts of the genome are junk and which are not.

For instance, what if "junk DNA" or non-functional DNA serves as a proving ground for viable mutations such that it increases the likelihood that an organism can produce new, adaptative offspring under rapidly changing environments? Or what if "junk DNA" through regulatory interactions facilitates an adaptative response by leveraging mutations which are influenced by environmental factors in offspring? The process of evolution might have selected for such provisionally influenced adaptations that might help to explain any gaps in the speed of evolution when rapid environment changes occur.

If memory serves, 50% of the human genome is transposons which are pieces of DNA that like to replicate themselves and reinsert into the genome. The better explanation seems to be that junk DNA is a pile of genes we no longer need (i.e. pseudogenes) and DNA parasites.

 

[Thermos aquaticus]

Larry Moran's blog "Sandwalk" is a great resource for all things genetics and curmudgeonly. He recently posted a list of papers worth reading if people are interested in the scientific debate about the ENCODE findings and junk DNA:

Sandwalk: Required reading for the junk DNA debate

These papers are peer reviewed papers, so they are quite dense and heavy on scientific jargon, just as a warning.

Larry is also famous for his Five Things You Should Know if You Want to Participate in the Junk DNA Debate :

1. Genetic Load
   Every newborn human baby has about 100 mutations not found in either parent. If most of our genome contained functional sequence information, then this would be an intolerable genetic load. Only a small percentage of our genome can contain important sequence information suggesting strongly that most of our genome is junk.
2. C-Value Paradox
   A comparison of genomes from closely related species shows that genome size can vary by a factor of ten or more. The only reasonable explanation is that most of the DNA in the larger genomes is junk.
3. Modern Evolutionary Theory
   Nothing in biology makes sense except in the light of population genetics. The modern understanding of evolution is perfectly consistent with the presence of large amounts of junk DNA in a genome.
4. Pseudogenes and broken genes are junk
   More than half of our genomes consists of pseudogenes, including broken transposons and bits and pieces of transposons. A few may have secondarily acquired a function but, to a first approximation, broken genes are junk.
5. Most of the genome is not conserved
   Most of the DNA sequences in large genomes is not conserved. These sequences diverge at a rate consistent with fixation of neutral alleles by random genetic drift. This strongly suggests that it does not have a function although one can't rule out some unknown function that doesn't depend on sequence.

 

[Thermos aquaticus]

#1 in the list above lists genetic load as a reason why most of the human genome is junk, so I thought I would discuss that a bit further.

Dan Graur has a peer reviewed paper on the subject:

"For the human population to maintain a constant size from generation to generation, an increase in fertility must compensate for the reduction in the mean fitness of the population caused, among others, by deleterious mutations. The required increase in fertility due to this mutational load depends on the number of sites in the genome that are functional, the mutation rate, and the fraction of deleterious mutations among all mutations in functional regions. These dependencies and the fact that there exists a maximum tolerable replacement level fertility can be used to put an upper limit on the fraction of the human genome that can be functional. Mutational load considerations lead to the conclusion that the functional fraction within the human genome cannot exceed 25%, and is probably considerably lower."
Upper Limit on the Functional Fraction of the Human Genome | Genome Biology and Evolution | Oxford Academic

There is a limit on the number of deleterious mutations that can occur in each generation for different species. If a large portion of the human genome is functional then this greatly increases the number of deleterious mutations in each generation. Therefore, there is an upper limit on what percentage of the human genome can be functional. As Dan Graur puts it in a different article:

"“For 80 percent of the human genome to be functional, each couple in the world would have to beget on average 15 children and all but two would have to die or fail to reproduce,” he wrote. “If we use the upper bound for the deleterious mutation rate (2 × 10−8 mutations per nucleotide per generation), then … the number of children that each couple would have to have to maintain a constant population size would exceed the number of stars in the visible universe by ten orders of magnitude.”
New Limits to Functional Portion of Human Genome Reported - University of Houston

The facts demonstrate that a large portion of the human genome has to be junk.

 

[Etritonakin]

Absolute newb here, but the absence of a thing often clearly reveals its value. If that "junk" DNA was literally absent, what do you think might happen?

 

[Cacotopia]

 

[Thermos aquaticus]

Absolute newb here, but the absence of a thing often clearly reveals its value. If that "junk" DNA was literally absent, what do you think might happen?

There are two examples to look at. First, they removed about 2 million bases of junk DNA from the mouse genome, and the mouse was unaffected.

Megabase deletions of gene deserts result in viable mice

Second, there is the bladderwort. This carnivorous plant has about the same number of genes as other plants and animals, but its genome is extremely tiny at just 0.083 billion bases. As a comparison, the human genome is 3 billion bases and the onion genome is 16 billion bases. The bladderwort genome is thought to have less than 5% junk DNA. In other words, the bladderwort has had almost all of its junk DNA removed and it does just fine.

"The compressed architecture of the U. gibba genome indicates that a small fraction of intergenic DNA, with few or no active retrotransposons, is sufficient to regulate and integrate all the processes required for the development and reproduction of a complex organism."
Architecture and evolution of a minute plant genome

 

[Etritonakin]

There are two examples to look at. First, they removed about 2 million bases of junk DNA from the mouse genome, and the mouse was unaffected.

Megabase deletions of gene deserts result in viable mice

Second, there is the bladderwort. This carnivorous plant has about the same number of genes as other plants and animals, but its genome is extremely tiny at just 0.083 billion bases. As a comparison, the human genome is 3 billion bases and the onion genome is 16 billion bases. The bladderwort genome is thought to have less than 5% junk DNA. In other words, the bladderwort has had almost all of its junk DNA removed and it does just fine.

"The compressed architecture of the U. gibba genome indicates that a small fraction of intergenic DNA, with few or no active retrotransposons, is sufficient to regulate and integrate all the processes required for the development and reproduction of a complex organism."
Architecture and evolution of a minute plant genome

Ok -so they did not remove the junk from "a" mouse, right? So... While it may not be doing anything special on a genetic level, it serves the purpose of making up -pretty much being -the mouse? Or what? And the viable mice made from non-junk.... did they have junk DNA?

 

[Thermos aquaticus]

Ok -so they did not remove the junk from "a" mouse, right?

They removed a relatively small chunk from the genome of a mouse. They then crossbred this one mouse with mice who didn't have the deletion, and then inbred the offspring. Since mice are diploid like we are they have two copies of their genome. You have to crossbreed and inbreed in order to get mice that have the deletion in both of their copies of the genome (i.e. homozygous). At the end of the experiment there were multiple mice that were homozygous for the 2 million base deletion of junk DNA.

So... While it may not be doing anything special on a genetic level, it serves the purpose of making up -pretty much being -the mouse? Or what? And the viable mice made from non-junk.... did they have junk DNA?

I guess it depends on what you mean by "being the mouse". The junk DNA that they removed didn't seem to have any role in forming the mouse during embryonic development or play any role in the physiological functions within the mouse. The mice with the deletion were indistinguishable from mice who had the junk DNA.

 

[Etritonakin]

They removed a relatively small chunk from the genome of a mouse. They then crossbred this one mouse with mice who didn't have the deletion, and then inbred the offspring. Since mice are diploid like we are they have two copies of their genome. You have to crossbreed and inbreed in order to get mice that have the deletion in both of their copies of the genome (i.e. homozygous). At the end of the experiment there were multiple mice that were homozygous for the 2 million base deletion of junk DNA.



I guess it depends on what you mean by "being the mouse". The junk DNA that they removed didn't seem to have any role in forming the mouse during embryonic development or play any role in the physiological functions within the mouse. The mice with the deletion were indistinguishable from mice who had the junk DNA.

I was being a bit of a smart alec -as in the junk DNA is still there being a part of us -though not necessarily doing anything interesting -and if all the junk was literally gone from a single human there would be less of that person.

 

[Thermos aquaticus]

I was being a bit of a smart alec -as in the junk DNA is still there being a part of us -though not necessarily doing anything interesting -and if all the junk was literally gone from a single human there would be less of that person.

I think we need to separate the idea of junk DNA and interesting DNA. Junk DNA can still be very, very interesting to different biologists. What we are saying when we label DNA as junk is that it doesn't affect the fitness of the organism. However, junk DNA can still hold valuable clues about a species' evolutionary history which makes it very interesting. Junk DNA can tell us about the history of transposon activity in different lineages. Junk DNA can tell us about the history of pseudogene formation which can tell us about the environmental pressures that a lineage has gone through (e.g. the human GULO pseudogene). Scientists aren't saying that we should ignore junk DNA.

I should also point out that human genomes do differ in size. There is a lot of variation in transposon insertions, ERVs, and other large indels. I doubt we would say that a human being is less of a human being because they lack a specific stretch of DNA found in other humans.

 

[Kenny]

It is still junk. Junk can do something and still be junk. Doing something is not the same as having function.



Nature would know if it had function. If it did have function then there would be conserved sequence.

Junk mean, I still don't know so I will call it junk. Junk like I said before:


Hidden Treasures in Junk DNA

realizing that there is no proof that it is nothing but "junk", I still hold the stronger hand.

another great example was the "appendix" which, at one time, they said it was useless... a leftover of what use to be, just junk. But science must be respected as they realize that what they once thought was right, they now know it's wrong;

What Does the Appendix Do?

 

[Thermos aquaticus]

Junk mean, I still don't know so I will call it junk.

We do know. We know that this DNA is accumulating mutations at a rate consistent with neutral drift. If this DNA had function there would be deleterious mutations that occur in the sequence which would be selected out resulting in a signal of sequence conservation. No sequence conservation is seen in about 90% of the human genome.

realizing that there is no proof that it is nothing but "junk", I still hold the stronger hand.

We do have tons of evidence that 90% of the human genome is junk:

1. Genetic Load
   Every newborn human baby has about 100 mutations not found in either parent. If most of our genome contained functional sequence information, then this would be an intolerable genetic load. Only a small percentage of our genome can contain important sequence information suggesting strongly that most of our genome is junk.
2. C-Value Paradox
   A comparison of genomes from closely related species shows that genome size can vary by a factor of ten or more. The only reasonable explanation is that most of the DNA in the larger genomes is junk.
3. Modern Evolutionary Theory
   Nothing in biology makes sense except in the light of population genetics. The modern understanding of evolution is perfectly consistent with the presence of large amounts of junk DNA in a genome.
4. Pseudogenes and broken genes are junk
   More than half of our genomes consists of pseudogenes, including broken transposons and bits and pieces of transposons. A few may have secondarily acquired a function but, to a first approximation, broken genes are junk.
5. Most of the genome is not conserved
   Most of the DNA sequences in large genomes is not conserved. These sequences diverge at a rate consistent with fixation of neutral alleles by random genetic drift. This strongly suggests that it does not have a function although one can't rule out some unknown function that doesn't depend on sequence.

another great example was the "appendix" which, at one time, they said it was useless...

False. It was said to be a rudimentary leftover of a well developed caecum. Whatever function it has now is a shadow of the function it once had as part of an organ that digested cellulose. You seem to have forgotten that vestigial means having a rudimentary function compared to the same organ in another species.

 

[Kenny]

We do know. We know that this DNA is accumulating mutations at a rate consistent with neutral drift. If this DNA had function there would be deleterious mutations that occur in the sequence which would be selected out resulting in a signal of sequence conservation. No sequence conservation is seen in about 90% of the human genome.



We do have tons of evidence that 90% of the human genome is junk:

1. Genetic Load
   Every newborn human baby has about 100 mutations not found in either parent. If most of our genome contained functional sequence information, then this would be an intolerable genetic load. Only a small percentage of our genome can contain important sequence information suggesting strongly that most of our genome is junk.
2. C-Value Paradox
   A comparison of genomes from closely related species shows that genome size can vary by a factor of ten or more. The only reasonable explanation is that most of the DNA in the larger genomes is junk.
3. Modern Evolutionary Theory
   Nothing in biology makes sense except in the light of population genetics. The modern understanding of evolution is perfectly consistent with the presence of large amounts of junk DNA in a genome.
4. Pseudogenes and broken genes are junk
   More than half of our genomes consists of pseudogenes, including broken transposons and bits and pieces of transposons. A few may have secondarily acquired a function but, to a first approximation, broken genes are junk.
5. Most of the genome is not conserved
   Most of the DNA sequences in large genomes is not conserved. These sequences diverge at a rate consistent with fixation of neutral alleles by random genetic drift. This strongly suggests that it does not have a function although one can't rule out some unknown function that doesn't depend on sequence.

False. It was said to be a rudimentary leftover of a well developed caecum. Whatever function it has now is a shadow of the function it once had as part of an organ that digested cellulose. You seem to have forgotten that vestigial means having a rudimentary function compared to the same organ in another species.

I think your position is false.

1) I gave you a site that doctors agree that the appendix does have a function. Rudimentary in comparison to what? Another species? Not a good comparison.

2) You are judging genomes by today's current understanding. it would be ludicrous to think we have all that we need to know about it. As I said, at one point they thought appedixes had no use... and now science has updated their position.

Let science continue! Or maybe just google:

'Junk DNA' Plays Crucial Role Holding Genomes Together

so much for junk.

 

[Thermos aquaticus]

I think your position is false.

1) I gave you a site that doctors agree that the appendix does have a function.

Vestigial organs can still have function.

Rudimentary in comparison to what? Another species? Not a good comparison.

Why is it not a good comparison?

"An organ serving for two purposes, may become rudimentary or utterly aborted for one, even the more important purpose, and remain perfectly efficient for the other.... [A]n organ may become rudimentary for its proper purpose, and be used for a distinct object."--Charles Darwin

2) You are judging genomes by today's current understanding. it would be ludicrous to think we have all that we need to know about it.

"It's ludicrous" is not a valid counter-argument. You need to actually demonstrate why the evidence we have right now is not enough to conclude that the vast majority of the human genome does not have sequence specific function.

As I said, at one point they thought appedixes had no use... and now science has updated their position.

At one time they stated that the appendix was a vestigial organ, and it still is. The human vermiform appendix still does not aid in the digestion of cellulose.

Let science continue!

Or maybe just google:

'Junk DNA' Plays Crucial Role Holding Genomes Together

so much for junk.

How much of the human genome is made up of satellite DNA? How does the bladderwort get by without its junk DNA?

 

[Kenny]

Vestigial organs can still have function.



Why is it not a good comparison?

"An organ serving for two purposes, may become rudimentary or utterly aborted for one, even the more important purpose, and remain perfectly efficient for the other.... [A]n organ may become rudimentary for its proper purpose, and be used for a distinct object."--Charles Darwin



"It's ludicrous" is not a valid counter-argument. You need to actually demonstrate why the evidence we have right now is not enough to conclude that the vast majority of the human genome does not have sequence specific function.



At one time they stated that the appendix was a vestigial organ, and it still is. The human vermiform appendix still does not aid in the digestion of cellulose.



How much of the human genome is made up of satellite DNA? How does the bladderwort get by without its junk DNA?

OK... you think science knows all there is to know about junk DNA no matter if I just proved that JUNK DNA holds genomes together... a necessary ingredient.

At this point all I can say is... to each his own.

 

[Thermos aquaticus]

OK... you think science knows all there is to know about junk DNA no matter if I just proved that JUNK DNA holds genomes together... a necessary ingredient.

Your article says that some of the satellite DNA holds genomes together. Finding a function for one tiny portion of junk DNA does not demonstrate that all junk DNA has function. You have never demonstrated that all of the junk DNA has function, and the evidence I have presented still applies. You have not addressed any of the evidence supporting the conclusion that most of the human genome is junk.

• Genetic Load
  Every newborn human baby has about 100 mutations not found in either parent. If most of our genome contained functional sequence information, then this would be an intolerable genetic load. Only a small percentage of our genome can contain important sequence information suggesting strongly that most of our genome is junk.

• C-Value Paradox
  A comparison of genomes from closely related species shows that genome size can vary by a factor of ten or more. The only reasonable explanation is that most of the DNA in the larger genomes is junk.

• Modern Evolutionary Theory
  Nothing in biology makes sense except in the light of population genetics. The modern understanding of evolution is perfectly consistent with the presence of large amounts of junk DNA in a genome.

• Pseudogenes and broken genes are junk
  More than half of our genomes consists of pseudogenes, including broken transposons and bits and pieces of transposons. A few may have secondarily acquired a function but, to a first approximation, broken genes are junk.

• Most of the genome is not conserved
  Most of the DNA sequences in large genomes is not conserved. These sequences diverge at a rate consistent with fixation of neutral alleles by random genetic drift. This strongly suggests that it does not have a function although one can't rule out some unknown function that doesn't depend on sequence.

 

[Kenny]

**sigh**

 

[Thermos aquaticus]

**sigh**

**sigh**

You still can't address the evidence.