Another poor response to ERV evidence for common ancestry by a creationist.

[Zaius137]

“I have already shown that a consensus sequence of HERV-K insertions produces a viable retrovirus. Their origin is retroviral. Also, I already addressed the regulatory features of HERV's, and I notice that you completely ignored it.”

Just as real as evolution, besides your imagination where else does it exist?[/quote]

It exists in the real world.

Here, we derived in silico the sequence of the putative ancestral “progenitor” element of one of the most recently amplified family—the HERV-K family—and constructed it. This element, Phoenix, produces viral particles that disclose all of the structural and functional properties of a bona-fide retrovirus, can infect mammalian, including human, cells, and integrate with the exact signature of the presently found endogenous HERV-K progeny.
Identification of an infectious progenitor for the multiple-copy HERV-K human endogenous retroelements
​

When they reconstructed the HERV-K insertions they produced infective retroviruses. This is not my imagination. This is real. Every post that you ignore this fact is a post that exposes your bias.
[/quote]

To LoudMouth..

I never said that man could not make these segments infectious. This is not at all different than the use of viruses to insert genes in foreign organisms (technology is well known). All that was apparently done here was to add enough coding to make these sections viral like. These segments may serve regulatory function in DNA that we do not yet understand yet can manipulate.

“Human endogenous retrovirus K (HERV-K) is the most intact retrovirus in the human genome. However, no single HERV-K provirus in the human genome today appears to be infectious.”

http://jvi.asm.org/content/83/2/1105.abstract


“ We found that HERV-KCon integrated preferentially in transcription units, in gene-rich regions, and near features associated with active transcription units and associated regulatory regions.”

http://jvi.asm.org/content/83/24/12790.abstract

Hey looks like it is fond of regulatory regions in the DNA… Why would that be?

As far as the HRV-K being a real virus, it is not. Never been found in the wild, yet some scientists still believe the infection happens to this day. The understanding is flawed because the hypothesis is not supported by the evidence.

 

[Zaius137]

"No, I don't. sfs explained why."

I still need an answer...

I used the proper birth rate formula and a common analogy from the accepted authority.

 

[Loudmouth]

"No, I don't. sfs explained why."

I still need an answer...

I used the proper birth rate formula and a common analogy from the accepted authority.

As I stated, sfs already gave you the answer. Here it is again:

"No, 133 offspring is the number that would be needed for every generation to have genetically flawless individuals in it. This is clearly not the case for humans, or for any other complex organism."--sfs

 

[Loudmouth]

I never said that man could not make these segments infectious. This is not at all different than the use of viruses to insert genes in foreign organisms (technology is well known). All that was apparently done here was to add enough coding to make these sections viral like. These segments may serve regulatory function in DNA that we do not yet understand yet can manipulate.

Of course ERV's have regulatory function. That is the entire point. The LTR's in retroviruses are regulatory regions that drive the transcription of the viral genome. You have once again pointed to evidence which supports the viral origin of ERV's.

Secondly, it is how man made HERV's infectious that evidences their viral origin. What they did was align several HERV-K insertions. This allowed them to find the mutations including indels and substitutions. When they removed the mutations the result was a fully functioning virus with the same insertion pattern as seen in HERV-K insertions. Man did not add DNA that wasn't already there.

“Human endogenous retrovirus K (HERV-K) is the most intact retrovirus in the human genome. However, no single HERV-K provirus in the human genome today appears to be infectious.”

http://jvi.asm.org/content/83/2/1105.abstract

That doesn't stop HERV-K insertions from being viral in origin.

“ We found that HERV-KCon integrated preferentially in transcription units, in gene-rich regions, and near features associated with active transcription units and associated regulatory regions.”

http://jvi.asm.org/content/83/24/12790.abstract

Hey looks like it is fond of regulatory regions in the DNA… Why would that be?

Because retroviruses are fond of inserting into transcription sites:

"For HIV the frequency of integration in transcription units ranged from 75% to 80%..."
Retroviral DNA Integration: ASLV, HIV, and MLV Show Distinct Target Site Preferences

You have pointed to another piece of evidence that points to the viral origin of ERV's.

As far as the HRV-K being a real virus, it is not.

Then why does a consensus sequence of HERV-K insertions produce a retrovirus? Why do HERV-K insertions have retroviral genes like viral envelope proteins (env), group specific antigen structural proteins (gag), and reverse polymerase (pol), and flanking viral promoters (LTR's)? Why is the arrangement of genes in HERV's identical to modern retroviruses?

Never been found in the wild, yet some scientists still believe the infection happens to this day.

Are you saying that retroviruses do not exist today?

The understanding is flawed because the hypothesis is not supported by the evidence.

I have pointed out several pieces of evidence that support the hypothesis. First, homology to modern retroviruses. Second, a consensus sequence of HERV-K insertions produces a functioning retrovirus. Third, the association of HERV-K insertions with transcription units which is consistent with modern HERV-K homologs as well as the reconstructed HERV-K virus.

 

[sfs]

"No, I don't. sfs explained why."

I still need an answer...

I used the proper birth rate formula and a common analogy from the accepted authority.

Even many geneticists are unaware of the subtleties involved in the concept of genetic load, and they often rely on simple models that do not correspond well to most biological reality. The kinds of genetic load calculation you're talking about implicitly assume that all selection is hard, that is, that a deleterious allele causes a loss of reproductive capacity regardless of what alleles it is competing with; the clearest example of such alleles are lethal mutations. In Bruce Wallace's words, "To calculate the proportion of individuals that will survive the combined effects of two, three, four, or more lethal genes, one need only obtain the product of the individual probabilities. The out- come is entirely reliable; it can be verified experimentally with relative ease. This type of selection I have called hard. The early calculations which were made in the name of genetic load were made according to rules which I regard as appropriate only in the case of hard selection." ("Hard and Soft Selection Revisited", Evolution, Sept 1975). A high rate of deleterious alleles under hard selection requires a very high fertility rate, since the only way to keep the population from extinction is by producing enough of the rare individuals with few or no deleterious alleles.

Under soft selection, on the other hand, reproductive fitness is only reduced in comparison with the best genotype actually in the population; examples of this would be any trait that affects the ability to compete for resources with other members of the same species. Again quoting Wallace, "In the absence of the optimal genotype, those with the highest fitnesses (rather than an abstraction) become the real standards of comparison; individuals with these geno- types tend to survive while other, less fit, individuals are eliminated from the population. The inferior fitness of certain genotypes is revealed by a direct comparison with others possessing higher fitnesses, not by a mathematician's calculation." Under soft selection, all that matters is the difference between the best and the worst combination of alleles in the population. A species can tolerate an indefinitely large number of such alleles segregating, since the total number has zero effect on the overall population fitness.

In the real world, some mutations clearly produce hard selection and some clearly produce soft selection, but the distribution between the two is not well understood. So any conclusions about the effect of the deleterious mutation rate on the viability of a species rely on information we simply do not have at present.

(Read Wallace's book, Fifty Years of Genetic Load for a much more involved account of the concepts.)

 

[Loudmouth]

In the real world, some mutations clearly produce hard selection and some clearly produce soft selection, but the distribution between the two is not well understood. So any conclusions about the effect of the deleterious mutation rate on the viability of a species rely on information we simply do not have at present.

(Read Wallace's book, Fifty Years of Genetic Load for a much more involved account of the concepts.)

I found an interesting paper that dealt with Muller's ratchet in asexual organisms (p-endosymbiots from insect species). The authors suggested that there is a cap to the number of slightly deleterious mutations that a population can carry.

"We find that Riesia is the youngest p-endosymbiont known to date, and has been associated with its louse hosts for only 13–25 My. Further, it is the fastest evolving p-endosymbiont with substitution rates of 19–34% per 50 My. When comparing Riesia to other insect p-endosymbionts, we find that nucleotide substitution rates decrease dramatically as the age of endosymbiosis increases. . . A decrease in nucleotide substitution rates over time suggests that selection may be limiting the effects of Muller's ratchet by removing individuals with the highest mutational loads and decreasing the rate at which new mutations become fixed. This countering effect of selection could slow the overall rate of endosymbiont extinction."

PLoS ONE: Mutational Meltdown in Primary Endosymbionts: Selection Limits Muller's Ratchet

 

[Naraoia]

*enjoying the free education*

 

[sfs]

I found an interesting paper that dealt with Muller's ratchet in asexual organisms (p-endosymbiots from insect species). The authors suggested that there is a cap to the number of slightly deleterious mutations that a population can carry.

"We find that Riesia is the youngest p-endosymbiont known to date, and has been associated with its louse hosts for only 13–25 My. Further, it is the fastest evolving p-endosymbiont with substitution rates of 19–34% per 50 My. When comparing Riesia to other insect p-endosymbionts, we find that nucleotide substitution rates decrease dramatically as the age of endosymbiosis increases. . . A decrease in nucleotide substitution rates over time suggests that selection may be limiting the effects of Muller's ratchet by removing individuals with the highest mutational loads and decreasing the rate at which new mutations become fixed. This countering effect of selection could slow the overall rate of endosymbiont extinction."

PLoS ONE: Mutational Meltdown in Primary Endosymbionts: Selection Limits Muller's Ratchet

I find the explanation in that paper somewhat confusing. Since Muller's Ratchet occurs when selection isn't able to keep up with deleterious mutations, it's not clear to me exactly what mechanism is they're proposing by which selection slows down the ratchet. There are mechanisms that make sense: as the genome degrades, additional deleterious alleles become more markedly deleterious, meaning selection can cope with them successfully, or selection favors a lower mutation rate, or selection favors the transfer of function to the host (and hence reduces the mutational target in the endosymbiont's genome), which would include the transfer of genes themselves to the host (something that has happened to a large extent in mitochondria). But this is not something I have thought or read about much.

Note that Muller's Ratchet is a particular subset of problems caused by deleterious mutations, in which the mutations actually become fixed in the population. It is really only a problem for very small populations of asexuals. The kind of problem that people like Nachman have talked about occurs even in larger, sexually reproducing populations. If you start with a genetically ideal (i.e. perfectly adapted) large population and turn on a high deleterious mutation rate, the mutations will initially occur too fast to be removed by selection, since very few offspring will be produced that don't have at least one new one; thus, the average number of deleterious alleles per individual will increase every generation. Eventually you will reach an equilibrium state, with individuals carrying some distribution of deleterious alleles. The individuals with the worst load fail to reproduce, and in doing so each removes a copy of many deleterious alleles at the same time -- more copies than are carried by the average member, which reduces the genetic load. At equilibrium, the number of deleterious allele copies removed this way equals the number introduced every generation by new mutation. (More precisely, the net improvement to fitness equals the net loss due to new mutations, since the selective effect of real mutations varies.) All of this can happen without any of the deleterious alleles reaching fixation.

In the case of soft selection, this process is not a problem for the species, since all members have a fairly large number of deleterious alleles, but the reproductive capacity of the group as a whole is not harmed; all that matters is the relative fitness of the worst-affected individuals compared to the best in the population. In the case of hard selection, however, this would be disastrous, since carrying even a few dozen deleterious alleles, each of which substantially reduced your ability to survive and reproduce, would spell genetic doom.

 

[Loudmouth]

There are mechanisms that make sense: as the genome degrades, additional deleterious alleles become more markedly deleterious, meaning selection can cope with them successfully, or selection favors a lower mutation rate, or selection favors the transfer of function to the host (and hence reduces the mutational target in the endosymbiont's genome), which would include the transfer of genes themselves to the host (something that has happened to a large extent in mitochondria). But this is not something I have thought or read about much.

The most interesting mechanism in the list is "additional deleterious alleles become more markedly deleterious". I think it is incorrect to assume that accumulation of slightly deleterious mutations will result in a linear reduction in fitness. There may be a situation where the proverbial last straw breaks the camel's back.

Note that Muller's Ratchet is a particular subset of problems caused by deleterious mutations, in which the mutations actually become fixed in the population. It is really only a problem for very small populations of asexuals.

More importantly, it is a worst case scenario in many ways. Sexual recombination solves many of these problems with respect accumulation of deleterious mutations. Even in a worst case scenario there seems to be a way to avoid genetic meltdown.

The kind of problem that people like Nachman have talked about occurs even in larger, sexually reproducing populations. If you start with a genetically ideal (i.e. perfectly adapted) large population and turn on a high deleterious mutation rate, the mutations will initially occur too fast to be removed by selection, since very few offspring will be produced that don't have at least one new one; thus, the average number of deleterious alleles per individual will increase every generation. Eventually you will reach an equilibrium state, with individuals carrying some distribution of deleterious alleles. The individuals with the worst load fail to reproduce, and in doing so each removes a copy of many deleterious alleles at the same time -- more copies than are carried by the average member, which reduces the genetic load. At equilibrium, the number of deleterious allele copies removed this way equals the number introduced every generation by new mutation. (More precisely, the net improvement to fitness equals the net loss due to new mutations, since the selective effect of real mutations varies.) All of this can happen without any of the deleterious alleles reaching fixation.

In the case of soft selection, this process is not a problem for the species, since all members have a fairly large number of deleterious alleles, but the reproductive capacity of the group as a whole is not harmed; all that matters is the relative fitness of the worst-affected individuals compared to the best in the population. In the case of hard selection, however, this would be disastrous, since carrying even a few dozen deleterious alleles, each of which substantially reduced your ability to survive and reproduce, would spell genetic doom.

Very well written and explained. However, it may be pearls before swine in some cases.

 

[Naraoia]

Hey, I'm not a pig! I can appreciate some shiny pearls!

 

[Greg1234]

As far as the HRV-K being a real virus, it is not. Never been found in the wild, yet some scientists still believe the infection happens to this day. The understanding is flawed because the hypothesis is not supported by the evidence.

It was already addressed by Dr Papadopoulos-Eleopulos too http://www.tig.org.za/EPE_SEP14.pdf (p. 15)

 

[Loudmouth]

It was already addressed by Dr Papadopoulos-Eleopulos too http://www.tig.org.za/EPE_SEP14.pdf (p. 15)

From page 15:

During the Parenzee trial, Gallo said a number of times, by definition, a particle can be considered to be a virus if, and only if, evidence exists that it is transmissible. Responding to a question put to him by Kevin Borick he stated: “…endogenous retroviruses aren’t viruses as your first witness [E.P-E] properly said, they are particles, they have never been transmitted. A virus is something that infects, that you prove goes from person. A to B. Short of that they are particles. Where a virus at least has to be transmitted in vitro in the laboratory, it goes from one cell to another, it’s never been demonstrated for endogenous retrovirus”.​

​

I have presented that proof. That proof is here:

Here, we derived in silico the sequence of the putative ancestral “progenitor” element of one of the most recently amplified family—the HERV-K family—and constructed it. This element, Phoenix, produces viral particles that disclose all of the structural and functional properties of a bona-fide retrovirus, can infect mammalian, including human, cells, and integrate with the exact signature of the presently found endogenous HERV-K progeny.
http://genome.cshlp.org/content/early/2006/10/31/gr.5565706.short
​

Added in edit: The only objection that the authors of your paper had to this paper was the name "endogenous retrovirus". They want them renamed to "endogenous retroelements". They do not challenge the fact that ERV's are the product of retroviral infection. They only challenge the idea that ERV's are viruses themselves.

 

[Zaius137]

Question for the LoudMouth…

Your entry…

Here, we derived in silico the sequence of the putative ancestral “progenitor” element of one of the most recently amplified family—the HERV-K family—and constructed it. This element, Phoenix, produces viral particles that disclose all of the structural and functional properties of a bona-fide retrovirus, can infect mammalian, including human, cells, and integrate with the exact signature of the presently found endogenous HERV-K progeny.
http://genome.cshlp.org/content/early/2006/10/31/gr.5565706.short


“MMTV is a betaretrovirus, the genus to which HERV-KCon belongs.”

The HERV-K was supposedly resurrected but does not act in the manner consistent with its supposed genus counterpart MMTV. They built a paleoretrovirus that is inconsistent in showing it is unable to integrate as the HERV-K insertions.

“MMTV, in contrast, encodes an integrase protein, and MMTV integration events show the usual sequence features associated with retroviral integration. It will be useful to obtain more data on integration site distributions from the betaretrovirus genus to clarify this puzzling observation.”

http://genesdev.cshlp.org/content/23/5/633.full

I believe that ERVs prove that evolution does not work because out of 200 thousand supposed ERVs we do not see a progression in (gradual evolution of) the viral infections. They are distinct variances of infection in a non linear progression. In essence there in no changes in the phenotype over long periods of time just like the fossils record of vertebrates do not show gradual changes in phenotype. Apes turned into humans but viruses stayed specific viruses.

How do you explain the viral fossils in our genome not showing evolution?

 

[Zaius137]

To (sfs)..

There are problems with soft selection deaths replacing background mortality…

“Under soft selection, all that matters is the difference between the best and the worst combination of alleles in the population. A species can tolerate an indefinitely large number of such alleles segregating, since the total number has zero effect on the overall population fitness.”

“As observed in computational systems, negative epistasis was tightly associated with higher tolerance to mutations (robustness). Thus, under a low selection pressure, a large fraction of mutations was initially tolerated (high robustness), but as mutations accumulated, their fitness toll increased, resulting in the observed negative epistasis.”

But is epistasis a good common observation?

“It remains unclear, however, whether synergistic epistasis is common enough to make such models generally applicable. Deleterious mutations may also interact antagonistically, such that the proportional reduction in fitness due to a mutation decreases as the number of background mutations increases.”

http://www.genetics.org/content/156/4/1635.full


Also Hominid studies were not done.

 

[sfs]

To (sfs)..

There are problems with soft selection deaths replacing background mortality…

“Under soft selection, all that matters is the difference between the best and the worst combination of alleles in the population. A species can tolerate an indefinitely large number of such alleles segregating, since the total number has zero effect on the overall population fitness.”

“As observed in computational systems, negative epistasis was tightly associated with higher tolerance to mutations (robustness). Thus, under a low selection pressure, a large fraction of mutations was initially tolerated (high robustness), but as mutations accumulated, their fitness toll increased, resulting in the observed negative epistasis.”

But is epistasis a good common observation?

“It remains unclear, however, whether synergistic epistasis is common enough to make such models generally applicable. Deleterious mutations may also interact antagonistically, such that the proportional reduction in fitness due to a mutation decreases as the number of background mutations increases.”

http://www.genetics.org/content/156/4/1635.full


Also Hominid studies were not done.

There may be problems with soft selection, but you haven't mentioned any of them.

 

[sfs]

The usual statement of the "paradox" only applies if the deleterious mutations are effectively lethal, which is obviously nonsense.

Correction: the usual statement of the "paradox" (that the genetic load is 1 - e[sup]-U[/sup]) applies regardless of the selection coefficients of the deleterious mutations (assuming hard selection, of course).

 

[Zaius137]

About the paradox?

“What proportion of nonsynonymous changes are neutral and what proportion are deleterious? The fraction that are neutral, fo, can be calculated by comparing the total mutation rate, µt, with the substitution rate, νo = foµt (KIMURA 1983Ahttp://www.genetics.org/content/156/1/297.full#R12#R12, KIMURA 1983Bhttp://www.genetics.org/content/156/1/297.full#R15#R15). The proportion that are deleterious is 1 - fo. Using this approach, KIMURA 1983Bhttp://www.genetics.org/content/156/1/297.full#R15#R15estimated that 86% of nonsynonymous substitutions are deleterious. A more conservative estimate is obtained by assuming that silent substitutions are entirely neutral and thus reflect the total mutation rate. Then the ratio of nonsynonymous to silent substitutions (Ka/Ks) estimates fo. This will be an underestimate to the extent that silent mutations are deleterious. Data from Ohta indicate that the average = 0.27 among 49 genes in primates (OHTA 1995 http://www.genetics.org/content/156/1/297.full#R38#R38). This suggests that 1.7% of the genome is subject to constraint [= 0.017]. The estimated genomic deleterious mutation rate, U, is thus ∼3 (U = 175 x 0.017), with a minimum value of 1.5 (U = 91 x 0.017) and a maximum value of 4 (U = 238 x 0.017), based on differences in divergence time,”





“The high deleterious mutation rate in humans presents a paradox. If mutations interact multiplicatively, the genetic load associated with such a high U would be intolerable in species with a low rate of reproduction (MULLER 1950 http://www.genetics.org/content/156/1/297.full#R45#R45; WALLACE 1981 http://www.genetics.org/content/156/1/297.full#R46#R46; CROW 1993 http://www.genetics.org/content/156/1/297.full#R47#R47; KONDRASHOV 1995 http://www.genetics.org/content/156/1/297.full#R48#R48; EYRE-WALKER and KEIGHTLEY 1999 http://www.genetics.org/content/156/1/297.full#R16#R16). The reduction in fitness (i.e., the genetic load) due to deleterious mutations with multiplicative effects is given by 1 - e-U (KIMURA and MORUYAMA 1966 http://www.genetics.org/content/156/1/297.full#R49#R49). For U = 3, the average fitness is reduced to 0.05, or put differently, each female would need to produce 40 offspring for 2 to survive and maintain the population at constant size.”

http://www.genetics.org/content/156/1/297.full


Greater problems are most likely to come to light in higher genome differences between chimps and humans. Evolution is only becoming more problematic, I refer to the irreconcilable observed mutation rates against the needed mutation rates that make a monkey into a man. You can only rob Peter of so much to pay Paul.

What if “U” is even higher?

 

[Zaius137]

D edit...

 

[Loudmouth]

Question for the LoudMouth…

Your entry…

Here, we derived in silico the sequence of the putative ancestral “progenitor” element of one of the most recently amplified family—the HERV-K family—and constructed it. This element, Phoenix, produces viral particles that disclose all of the structural and functional properties of a bona-fide retrovirus, can infect mammalian, including human, cells, and integrate with the exact signature of the presently found endogenous HERV-K progeny.
http://genome.cshlp.org/content/early/2006/10/31/gr.5565706.short


“MMTV is a betaretrovirus, the genus to which HERV-KCon belongs.”

The HERV-K was supposedly resurrected but does not act in the manner consistent with its supposed genus counterpart MMTV.

But it does act like ERV-K as evidenced by the insertion pattern:

"This element, Phoenix, produces viral particles that disclose all of the structural and functional properties of a bona-fide retrovirus, can infect mammalian, including human, cells, and integrate with the exact signature of the presently found endogenous HERV-K progeny."

Why is this not evidence that HERV-K are derived from a retrovirus?

They built a paleoretrovirus that is inconsistent in showing it is unable to integrate as the HERV-K insertions.

Perhaps you need to reread the abstract? They stated that the insertion pattern of the reconstructed retrovirus has the same insertion pattern as the HERV-K insertions found in primate genomes. That it inserts differently than a related virus is irrelevant.

I believe that ERVs prove that evolution does not work because out of 200 thousand supposed ERVs we do not see a progression in (gradual evolution of) the viral infections. They are distinct variances of infection in a non linear progression. In essence there in no changes in the phenotype over long periods of time just like the fossils record of vertebrates do not show gradual changes in phenotype. Apes turned into humans but viruses stayed specific viruses.

Why would a successful virus need to change?

How do you explain the viral fossils in our genome not showing evolution?

How do you explain viral fossils demonstrating shared ancestry between humans and other apes?

 

[Loudmouth]

“The high deleterious mutation rate in humans presents a paradox. If mutations interact multiplicatively, the genetic load associated with such a high U would be intolerable in species with a low rate of reproduction (MULLER 1950 ; WALLACE 1981 ; CROW 1993 ; KONDRASHOV 1995 ; EYRE-WALKER and KEIGHTLEY 1999 ). The reduction in fitness (i.e., the genetic load) due to deleterious mutations with multiplicative effects is given by 1 - e-U (KIMURA and MORUYAMA 1966 ). For U = 3, the average fitness is reduced to 0.05, or put differently, each female would need to produce 40 offspring for 2 to survive and maintain the population at constant size.”

http://www.genetics.org/content/156/1/297.full

Why don't you quote the section after that where they list mechanisms that solve the problem?

Evolution is only becoming more problematic, I refer to the irreconcilable observed mutation rates against the needed mutation rates that make a monkey into a man.

Citation please.