Humans Evolving Negativley

[lucaspa]

Even if more mutations were detrimental than beificial, this doe not mean that they will lower the fitness of an organism. In sexual selection each organism gets 2 coppies of their genome, each from a different parent. Any bad mutations on one can be canceled out by the other. Also DNA has many repair mechanisms that can detect and either repair the mutation, or switch it off so it doesn't cause a problem.

 

Let me take these in reverse order:

 

1. Mutations are a mistake in copying DNA. To have a mutation means that the repair mechanisms have failed. Nor does DNA have the ability to switch off a mutation -- the transcription factors can't tell that a particular gene has been mutated. The organism has to live with the results.

 

2. It is true that, in some cases, only one copy of a gene is expressed. But again, as far as I know, DNA doesn't have the ability to tell which is which. In the cases where the effect of a detrimental mutation is reduced, it is because both copies of the gene are expressed, and the number of "good" proteins helps mitigate the effects of the proteins produced by the detrimental mutation. Osteogenesis imperfecta is one example of this. Get 2 bad copies and the genetic disease is very bad. Get one bad copy and the severity is much, much less.

 

3. Detrimental mutations do lower the fitness of an individual. This does not mean an effect on the population, because the individuals unlucky enough to get the detrimental mutation are weeded from the population and the frequency (number of individuals with that mutation) drops. Eventually, the frequency will go to 0. That's the selection part of natural selection. On the other side, a beneficial mutation will eventually reach a frequency of 1 -- every individual will have it. This is what biologists mean when they say a trait is "fixed".

 

So the fact that there are many more bad mutations, than good mutations does not mean that the organism's gene pool will nessisarily become corrupted.

 

But the data is not that there are more bad mutations than good. Rather, that there are vastly more neutral or beneficial mutations than outright bad ones. However the point is good: selection works to eliminate bad mutations and preserves good ones.

 

The point of the OP, however, was that humans were not subject to selection anymore. Thus, "detrimental" mutations were not being eliminated by selection.

[lucaspa]

There is no such thing as negative evolution. We are always evolving toward some set of selection criteria, never away.

 

Good point. You are addressing the judgement call of the OP. The poster has the idea that some traits are absolutely "good" -- such as 20/20 eyesight -- and some traits are absolutely "bad" -- such as nearsightedness. Since we compensate for nearsightedness with glasses, the OP feels that this "bad" trait is accumulating in the population.

 

Since the physcial "fitness" of a human is no longer critical to its survival, this is not being selected-for anymore (or much, at least).

 

What we are doing is moving from physical evolution to social evolution. It is social traits that now determine who breeds and who does not.

 

A couple of years ago there was a study showing that the increase in height in humans was due to sexual selection: people pick tall mates.

 

In isolated populations such as the Andean and Himalayan highlanders, there is still selection for physical characteristics. Several studies have shown that each population is evolving (different) adaptations to living at high altitudes.

 

Can you quote any studies about social traits and mating or is this your gut feeling?

[Dark Photon]

some very good points.

 

 

with the state of things human evolution will come to a abrupt end very soon.

[Edtharan]

To have a mutation means that the repair mechanisms have failed. Nor does DNA have the ability to switch off a mutation -- the transcription factors can't tell that a particular gene has been mutated. The organism has to live with the results.

The expression of a mutation is a failure of the repair systems. A mutation is not. Cell in your body suffer mutations each time it replicates, but most these mutations are repaired (the ones that don't might cause the cell to die or turn cancerous.)

 

Nor does DNA have the ability to switch off a mutation -- the transcription factors can't tell that a particular gene has been mutated.

There are methods that a cell can use to switch off certain sections of DNA. This is why you can have different cells form from the single egg cell. A cell can detect damage like mutation and can use this to either attempt repair, or cause its self to die (so as to stop a cancer forming). If this fails it can lead to cancer.

 

Remember every cell has another copy of that chromosome that it can use as a template to detect some errors and other cells can send protines, rna and other chemicls through to a nearby cell that can also be used in this fassion (just compareing protiens can be enough - eg if two cells have differnet protien expressions that can both die as one of them is in error and there are other cells can replace them).

 

It is true that, in some cases, only one copy of a gene is expressed. But again, as far as I know, DNA doesn't have the ability to tell which is which.

Each cell ingerits not only the DNA from it parents, but als some of the protines and other chemicals too. This means it does have some point of reference as to what protiens and chemicals should be produced. So by this method it can detect mutations in its DNA.

 

But the data is not that there are more bad mutations than good. Rather, that there are vastly more neutral or beneficial mutations than outright bad ones.

But there are so many methods that a cell can use to catch bad mutations and even attempt to repare them that not all bad mutations are expressed. So if all you are going on is expressed mutations, then you are only sampeling a small fraction of the mutations that occure.

[lucaspa]

The expression[/i'] of a mutation is a failure of the repair systems. A mutation is not. Cell in your body suffer mutations each time it replicates, but most these mutations are repaired (the ones that don't might cause the cell to die or turn cancerous.)

 

If they are repaired, they are not "mutations" as we are using the term. "mutation

 

1. A change in form, quality or some other characteristic.

 

2. (Science: genetics) A permanent transmissible change in the genetic material, usually in a single gene. Also, an individual exhibiting such a change." http://www.biology-online.org/dictionary/Mutations

 

See? An error that is repaired is not a "permanent" change, is it? It was temporary before it was repaired.

 

There are methods that a cell can use to switch off certain sections of DNA. This is why you can have different cells form from the single egg cell. A cell can detect damage like mutation and can use this to either attempt repair, or cause its self to die (so as to stop a cancer forming). If this fails it can lead to cancer.

 

Apples and oranges. Yes, cells in multicellular organisms do turn off some genes and turn on others so that cells can specialize. Since I work with adult stem cells, I am familiar with that literature. However, we aren't speaking of those mechanisms. We are speaking of turning off a mutated protein. This doesn't happen. If the type I collage gene -- a necessary and specific gene for some tissues such as tendon, ligament, and bone -- is mutated, the body doesn't have the ability to turn it off. The individual has to live with the result.

 

Or take the hemoglobin gene -- specific for red blood cells. If it is mutated to the sickle cell form, the individual has to live with that result. A recent case in Sweden illustrates that. The individual exhibited the symptoms of sickle cell anemia, but no one considered it because, well, this was Sweden. Nordics didn't carry the sickle cell allele. But this was a brand new mutation and the individual did indeed have sickle cell.

 

Remember every cell has another copy of that chromosome that it can use as a template to detect some errors and other cells can send protines, rna and other chemicls through to a nearby cell that can also be used in this fassion (just compareing protiens can be enough - eg if two cells have differnet protien expressions that can both die as one of them is in error and there are other cells can replace them).

 

1. Can you quote me any paper where the cell uses one chromosome to detect errors on the other? I don't know of any. As I say, type II osteogenesis imperfecta is much milder than type I because there is one good copy on one chromosome. If your hypothesis were correct, this type of OI would not exist, because the good copy would be used to correct the bad one.

 

2. Can you quote a paper where RNA and/or proteins are passed from cell to cell in order to correct defects in DNA?

 

3. Again, you are talking apples and oranges. Remember, mutations we are talking about are not in cells in the adult, but in the sex cells. That is in either the sperm or the ovum. When they get together, they form the fertilized ovum -- the cell that is going to give rise to ALL the cells in the body. So ALL the cells are going to have the mutation. There is are no "other cells to replace them".

 

Each cell ingerits not only the DNA from it parents, but als some of the protines and other chemicals too. This means it does have some point of reference as to what protiens and chemicals should be produced. So by this method it can detect mutations in its DNA.

 

Translation of DNA to protein goes only 1 way. It doesn't go from amino acid sequence in proteins to base sequence in DNA. Again, can you please cite some papers for this? I have never encountered mention of this phenomenon in my 30 years as a biochemist.

 

But there are so many methods that a cell can use to catch bad mutations and even attempt to repare them that not all bad mutations are expressed. So if all you are going on is expressed mutations, then you are only sampeling a small fraction of the mutations that occure.

 

As I read this, I think you are confused between what happens with cancer and mutations as they are used in evolution. Yes, mutations can happen in adult cells -- the somatic cells. And yes, in most cases the mutations cause an abnormal cell which either 1) undergoes apoptosis (programmed cell death) or 2) destruction by the immune system. The rare ones that do neither result in cancer.

 

HOWEVER, we are talking about mutations in the sex cells -- sperm or ovum. These are errors in copying DNA that are not corrected by the intrinsic repair mechanisms. Errors that are corrected are not mutations. Those repair mechanisms are VERY good, but they cannot be perfect. Such perfection would be a violation of the Second Law of Thermodynamics. So, in that case we have a permanent error that is going to be in ALL the cells of the new individual -- because all the cells came from the fertilized ovum. Many of those errors are bad enough that the embryo fails to develop -- that is the cause of most miscarriages. But the rest reside in the individual and make that individual slightly different from all the other individuals in that generation.

 

For a genome the size of the human genome, there will be about 2 mutations per genome. That is, you have 2 mutations. So do I. So does everyone else on the planet.

[Edtharan]

If they are repaired, they are not "mutations" as we are using the term. "mutation

If you switch a light on then off, it does not mean that the light was not on. The fact that the DNA was changed means a mutation took place, but then it wa repaired. Permanant mutations is another thing altogether. I think that here we are arguing over a dictionary definition rahter then the actual meaning in context so I will not persue this any further.

 

RNA and/or proteins are passed from cell to cell in order to correct defects in DNA?

Some protiens can cause a mutated protien to change into the correct one. It can also go the otherway as in a Prion. These protines can be passed on from Mother to child as these protiens may exist in the egg cells.

 

Again, you are talking apples and oranges. Remember, mutations we are talking about are not in cells in the adult, but in the sex cells. That is in either the sperm or the ovum. When they get together, they form the fertilized ovum -- the cell that is going to give rise to ALL the cells in the body. So ALL the cells are going to have the mutation. There is are no "other cells to replace them".

As I said, "Whenever a cell devides". I did not specifically say germ cells. Mutations can arrise in cells that are not sperm or eggs, not just at conception.

 

Translation of DNA to protein goes only 1 way.

Protiens and other chemical scan influence DNA. They can cause mutations or even cause the DNA to fold/pack differently. These can cause the DNA of the organism to express its self differently. I was not saying that the protiens changed the DNA "letters".

[lucaspa]

If you switch a light on then off, it does not mean that the light was not on. The fact that the DNA was changed means a mutation took place, but then it wa repaired. Permanant mutations is another thing altogether. I think that here we are arguing over a dictionary definition rahter then the actual meaning in context so I will not persue this any further.

 

No, we are arguing over the meaning. Mutations are permanent. What you are talking about are errors that occur during the replication of DNA that are then corrected still during the replication process. Or the methylation and de-methylation of DNA.

 

But, in genetics, the meaning of "mutation" is a permanent change in the DNA. If the light was on and then off, then the light being "on" is a temporary situation, not a permanent one. This happens during gene expression. Often genes are expressed "transiently", that is, turned on and then off. But the sequence of bases in DNA that is a mutation stays that same sequence.

 

 

Some protiens can cause a mutated protien to change into the correct one. It can also go the otherway as in a Prion. These protines can be passed on from Mother to child as these protiens may exist in the egg cells.

 

Please cite the paper that changes a "mutated protein" into the correct one. As I say, I've never seen this.

 

As I said, "Whenever a cell devides". I did not specifically say germ cells. Mutations can arrise in cells that are not sperm or eggs, not just at conception.

 

This is where you are confusing cancer with the OP. The OP was clear that an individual was "born with" the mutation. This is mutation in the classic genetic and evolutionary sense. Not changes that occur in some cells in the adult during the transformation of a normal cell to a cancer cell.

 

Protiens and other chemical scan influence DNA. They can cause mutations or even cause the DNA to fold/pack differently. These can cause the DNA of the organism to express its self differently. I was not saying that the protiens changed the DNA "letters".

 

But, in order to "correct a mutation" changing the DNA letters is EXACTLY what has to happen. That's what a mutation is: a permanent change of the sequence of bases in DNA.

 

What you are talking about is expression of the gene. When is it expressed, how many mRNA copies are made, are both copies of the gene turned on, etc? This is no longer correction of mutations, but gene expression.

 

Apples and oranges.

[lucaspa]

Protiens and other chemical scan influence DNA. They can cause mutations or even cause the DNA to fold/pack differently. These can cause the DNA of the organism to express its self differently. I was not saying that the protiens changed the DNA "letters".

 

This isn't translation. Translation is converting the "letters" in DNA to amino acids in proteins. You don't go the other way: taking the amino acids in a protein and converting them to the "letters" (of 3 base codons) in DNA.

 

Again, what you are talking about is expression. Folding/packing is involved with whether the DNA can be transcribed to messenger RNA. If tightly packed, no transcription.

 

Now, when you speak of "mutation" you are talking a change in the sequence of bases. BUT, this isn't a reflection of the amino acids in the protein. Instead, it is a "random" change unrelated to the function of the gene.

[Edtharan]

Please cite the paper that changes a "mutated protein" into the correct one. As I say, I've never seen this.

I have been looking for the reference to the paper, but am not able to find it. It was around 5 or 6 years ago (so I can;t bring the exact details to mind). If I remember correctly it was an article in New Scientist or some other magazine like it, that referenced an aricle in "Nature".

 

In the aricle they described research into the "Mad Cow" deseaes and how they worked. Mad Cow is caused by a missfoled protein that causes correctly folded proteins to be folled in the incorrect way (thus spreading the desease). The reserchers also found that some proteins cause missfolded proteins to be folded correctly. This research answered one of the puszzles about protein folding and how protiens "knew" how to fold correctly.

[lucaspa]

I have been looking for the reference to the paper' date=' but am not able to find it. It was around 5 or 6 years ago (so I can;t bring the exact details to mind). If I remember correctly it was an article in New Scientist or some other magazine like it, that referenced an aricle in "Nature".

 

In the aricle they described research into the "Mad Cow" deseaes and how they worked. Mad Cow is caused by a missfoled protein that causes correctly folded proteins to be folled in the incorrect way (thus spreading the desease). The reserchers also found that some proteins cause missfolded proteins to be folded correctly. This research answered one of the puszzles about protein folding and how protiens "knew" how to fold correctly.[/quote']

 

OK, this is different than correcting a "mutated protein". A mutated protein is one where the amino acids have been changed by a mutation to the sequence of bases in the DNA.

 

When translation occurs, the DNA is first copied to messenger RNA. The mRNA is then moved (translocated) from the nucleus to the cytoplasm and to the ribosome. The ribosome actually makes the protein, but does so by adding one amino acid at a time. Thus the protein comes out as a linear chain. Do you know about R groups on amino acids?

 

Anyway, because of the differnt ways R groups interact with water, the linear protein chain folds into a 3 D structure. However, sometimes they need help. There is a class of proteins called "chaperones" that help proteins fold. They were first discovered in looking at transport of proteins into mitochondria. The proteins unfolded to get thru the membrane, and then had to re-fold:

 

"Since the 1950s, scientists have known that the information necessary for a protein to fold properly is encoded in its aminoacid sequence. However, in the past 15 years, researchers have discovered that matters are not quite that simple within cells. “In 1987, we were studying how proteins got into mitochondria”, says Arthur Horwich (Yale University School of Medicine, New Haven, CT, USA). “It was becoming clear that for this to happen, proteins had to unfold so that they could get through the mitochondrial membranes rather like a strand of spaghetti. The question we and others asked was ‘Do proteins spontaneously refold once they get into mitochondria or is some sort of machine needed?’”

 

Cells were soon discovered to have several such machines—called chaperones—that assist protein folding particularly when cells are exposed to stresses such as heat. Chaperones, explains Horwich, are proteins that have hydrophobic surfaces that recognise and bind to the exposed hydrophobic surfaces of improperly folded proteins. “This prevents non-native [misfolded] protein molecules making wrongful interactions with other molecules of the same sort”, a process that could cause aggregation, says Horwich. “Small proteins probably don't normally need chaperones to fold, but large complex proteins need kinetic assistance." " Chaperones: keeping a close eye on protein folding Jane Bradbury, Lancet 361: 5 April 2003, Pages 1194-1195

 

What is confusing you is that several researchers are hoping to use chaperones to combat genetic diseases where they think the effect of the mutation is to cause misfolding of the protein. They want to design chaperones to cause the misfolded protein to refold the correct way. This would, in these particular cases negate the effect of the mutation. It doesn't "correct the mutation" = changing the DNA back to what it should be, but it would stop the disease effect of the mutation by restoring the protein to the correct folding.

 

The offspring of a person with the genetic disease would also have the disease, because the DNA had not been changed.

 

There are several problems:

1. To correct the folding, the chaperone has to associate with the protein. But then the protein can't function. So the chaperone would have to dissociate after correct folding was achieved. Will this happen?

 

2. How long would the corrected folding last? After all, the incorrect folding was the way that the protein wanted to fold -- it was the preferred folding and reprsented the lowest energy state. So it follows that the protein would unfold a little and then refold back to the non-fuctional folding.

 

3. Will the chaperone be able to help at all? "once mutation enters the scene, the ability of any protein to reach its native, active state is strongly affected.” It may be impossible for even a designed chaperone to help.

 

Now, I have seen recent research that indicates hopeful preliminary data on designed chaperones to lessen the effect of a few genetic diseases.

 

"Also under investigation is whether molecular chaperones—the cell's ownchaperones—can be used to fix protein misfolding problems. Ulrich Hartl (Max Planck Institute of Biochemistry, Martinsried, Germany) is optimistic. He is studying polyglutamine diseases, in which genetic expansions of the nucleotide triplet CAG lead to long glutamine stretches in the encoded protein.

 

“When the polyglutamine expansion in proteins such as huntingtin exceeds about 40residues”, he explains, “its normal random coil-like structure adopts a conformation rich in β sheets. These can align regularly and form the fibrillar amyloid structures responsible for the disease process.” Hartl has shown that in vitro and in cells, increased expression of molecular chaperones—in particular, Hsp70—can suppress the cellular toxicity of polyglutamine proteins.

 

To achieve Hsp70 upregulation, Hartl used the drug geldanamycin, as has Nancy Bonini (University of Pennsylvania, Philadelphia, PA, USA) in her in-vivo studies on neurodegeneration. “We had already shown that Hsp70 expression in a fly model of a polyglutamine disease suppressed pathogenicity. As a proof-of-principle we wanted to see whether a drug that could boost chaperone activity could do the same.”

 

Working with a drosophila model of Parkinson's disease, Bonini found that geldanamycin treatment protected the flies against dopaminergic neuron loss.

 

Geldanamycin is too toxic for clinical use, particularly given that for conditions such as Huntington's or Parkinson's disease repeated doses would be needed to prevent the toxic effects of protein aggregation. And both Hartl and Bonini comment that no-one knows what other effects tampering with Hsp70 expression will have."

 

But none of this happens naturally. It requires human intervention and, to emphasize once again, the mutation is NOT corrected in the sense that the DNA is changed back to its original, pre-mutation sequence.

[Edtharan]

Ahh, ok, I undestand now. Thanks.

 

Although I do remember reading an articla in new scientist (about a year ago I think) about changes in protiens and other non DNA changes being passed on to the ofspring (in the aricl I it even said that some foods might have chemicals that can cause these changes).

 

I can't remember exactly when, and I don't have the magazine anymore, but it does seem that some non-DNA changes might be passed to the ofspring.

[lucaspa]

Ahh' date=' ok, I undestand now. Thanks.

 

Although I do remember reading an articla in new scientist (about a year ago I think) about changes in protiens and other non DNA changes being passed on to the ofspring (in the aricl I it even said that some foods might have chemicals that can cause these changes).

 

I can't remember exactly when, and I don't have the magazine anymore, but it does seem that some non-DNA changes might be passed to the ofspring.[/quote']

 

I subscribe to New Scientist (it's free, so you can also) and get New Scientist in digital form. If you can even get an idea of the month last year, I can look the article up. Absent the article, I don't see how non-DNA changes can be passed to an offspring.

 

Some foods contain mutagens for DNA -- grilled meat is one of these. Other foods contain anti-oxidants. These can help prevent mutations to DNA. So a person eating a lot of anti-oxidants is less likely to have these oxidative changes to DNA. Other than that, I can't think of anything I have read that would be even close to what you are saying.