Two human proteins found to affect how 'jumping gene' gets around

Nov 21, 2013
This is a dramatic rendering of a technique used in this study, in which frozen cells were broken open to reveal interactions among the molecules inside. Credit: Sigrid Knemeyer/Johns Hopkins University School of Medicine

Using a new method to catch elusive "jumping genes" in the act, researchers have found two human proteins that are used by one type of DNA to replicate itself and move from place to place. The discovery, described in the Nov. 21 issue of Cell, breaks new ground, they say, in understanding the arms race between a jumping gene driven to colonize new areas of the human genome and cells working to limit the risk posed by such volatile bits of DNA.

Jumping genes, more formally known as transposons or transposable elements, are DNA segments with the blueprints for proteins that help to either copy the segment or remove it, then insert it into a new place in the genome. Human genomes are littered with the remnants of ancient , but because cells have an interest in limiting such trespasses, they have evolved ways to regulate them. Most jumping genes have mutated and can no longer move, but these "rusting hulks" are still passed down from generation to generation.

One exception is a jumping gene called L1, which has been so successful that copies of it make up about 20 percent of human DNA. While many of these copies are now mutated and dormant, others are still active and thus the subject of much interest from geneticists.

"Human cells have evolved ways of limiting jumping genes' activity, since the more frequently they move, the more likely they are to disrupt an important gene and cause serious damage," says Lixin Dai, Ph.D., a postdoctoral associate at the Johns Hopkins Institute for Basic Biomedical Sciences, who led the study. To find out more about how cells control L1 and what tricks the jumping gene uses to get around these defenses, Dai and others in the laboratory of Jef Boeke, Ph.D., first induced lab-grown human cells to make large amounts of the proteins for which L1 contains the blueprints. As expected, the two types of L1 protein joined with human proteins and genetic material called RNA to form so-called ribonucleoprotein particle complexes, which L1 uses to "jump."

To find out which human proteins interact with ribonucleoproteins – and are therefore likely to have a role in either tamping down its activity or helping it along – Boeke's team collaborated with researchers at The Rockefeller University who had developed a technique for fast-freezing yeast with liquid nitrogen, then grinding it up for analysis with steel balls and very rapidly pulling out the ribonucleoproteins with tiny magnetic particles. "It's a good way of preserving the interactions," Dai says.

Adapting this powerful technique to human cells, the team found 37 proteins that appear to interact with the ribonucleoprotein, and they selected two for further analysis. One of these, UPF1, is known for its role in quality control; it monitors the RNA transcripts that carry instructions from DNA to the cell's protein-making machinery and destroys those with mistakes. In this case, Dai says, UPF1 binds to the L1 ribonucleoprotein, probably because L1 RNA contains instructions for two proteins rather than one – a red flag for UPF1. When the researchers disabled the UPF1 gene, cells produced more L1 RNA and protein. But they still haven't figured out exactly how UPF1 interacts with the ribonucleoprotein, Dai says.

The other , PCNA, helps to copy DNA strands before a cell divides into two. The researchers found that PCNA interacts with a critical segment of one of the ribonucleoprotein's L1 proteins; when they tried altering that section, L1 could no longer jump. In contrast to UPF1's role in suppressing L1 activity, Dai says PCNA seems to have been co-opted into helping the jumping gene, perhaps by repairing gaps left in human DNA after L1 splices itself into a new spot.

Dai notes that these discoveries would not have been possible without two methods pioneered in this study: growing large quantities of human cells and inducing them to make ribonucleoprotein, and adapting the fast-freezing technique to study interactions in . He expects that these methods will enable biologists to greatly increase their understanding of L1, a jumping gene that has played a key role in the evolution of the human genome and whose activity has been implicated in some cancers.

"Our study shows how the jumping gene tries to be smart and get around the host cell's control mechanisms, and how the host tries to minimize its activity," Dai says. "We're looking forward to learning more about this ."

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JVK
1 / 5 (9) Nov 21, 2013
Mutation-initiated natural selection seems to be fading away into the obscurity of a flawed paradigm never supported by experimental evidence. Doesn't it?

Does anyone know who was responsible for the decade-long delay?

http://mcb.asm.or...abstract

http://www.socioa...53/27989
RealScience
5 / 5 (3) Nov 21, 2013
Mutation-initiated natural selection seems to be fading away into the obscurity of a flawed paradigm never supported by experimental evidence. Doesn't it?


No, it doesn't seem to be fading away.

For example, this article contains an example of a class of mutations that is selected for because it is beneficial (the mutation of a jumping gene so that it can no longer jump is typically beneficial to the host, and thus such mutations are selected FOR , and thus many such mutations have accumulated in our genomes).

So in contrast to your claim of no evidence, this very article contains evidence for natural selection action on mutations (selecting for in some cases and against in others).
JVK
1 / 5 (9) Nov 22, 2013
Your simple-minded acceptance of what you think is "evidence" exemplifies the problem with the flawed paradigm, which was never supported by EXPERIMENTAL evidence. My focus has been on EXPERIMENTAL evidence, which is what I clearly noted in my comment. For example, EXPERIMENTAL evidence that characterized TE content in a butterfly genome suggests diversity of all lepidopteran genomes is nutrient-dependent and pheromone-controlled as does all EXPERIMENTAL evidence in all species. http://www.mobile...abstract

If you supply EXPERIMENTAL evidence that nutrients are not required for species diversity or that the metabolism of the nutrients does not control the physiology of reproduction, we could compare that EXPERIMENTAL evidence to the theoretical evidence of automagical selection for the accumulation of mutations, which no EXPERIMENTAL evidence suggests are fixed in the genome of any species.

RealScience
5 / 5 (3) Nov 22, 2013
@JVK - your simple-minded blindness to the evidence exemplifies the problem with your lack of open-mindedness to the role of mutations.

"Natural selection" works in NATURE, and nature has been running EXPERIMENTS on a grand scale for far more generations than we have had time to in labs. Accumulation of beneficial mutations through natural selection is a long process requiring many generations, this millions-of-generations experiment on millions of subjects (even for a single macroscopic species), so nature is the logical place to look.

Which part of' NATURAL selection did you fail to understand?

Regarding nutrients: of course nutrients also play a part (being essential for life). But that does not conflict with a role for mutations, so why are you attempting to change the subject from your original statement?
JVK
1 / 5 (9) Nov 22, 2013
If you think 'natural selection' works in NATURE, please provide experimental evidence to support that theory.

The part of NATURAL selection I don't understand is the part that is automagical, with no experimental evidence that shows how mutations selected over millions of years could ever be beneficial -- especially since no evidence suggests they are ever fixed in the genome.

You take my comments on transposable elements in the context of a failed paradigm down to the lowest level of debate I can imagine. I offer experimental evidence from moths and butterflies for nutrient-dependent pheromone-controlled adaptive evolution, and you simply claim "natural selection" is somehow doing something with mutations.

You're not very bright, are you? Please tell us if you believe that bird predation caused natural selection for mutated color changes in peppered moths, and that snake predation caused evolution of the human brain? Alternatively, provide experimental evidence!
RealScience
5 / 5 (3) Nov 22, 2013
I offer experimental evidence from moths and butterflies for nutrient-dependent pheromone-controlled adaptive evolution


And how is that evidence that mutations are never selected for?

The part of NATURAL selection I don't understand is the part that is automagical, with no experimental evidence that shows how mutations selected over millions of years could ever be beneficial -- especially since no evidence suggests they are ever fixed in the genome.


I have already pointed out to you the example of several different mutations being selected FOR in malaria tolerance. (http://phys.org/n...ml#jCp).

Do you maintain that all present genes of all multicellular creatures, in all their variety, were in their unicellular ancestors? If not, then explain the variety genes present today.
JVK
1 / 5 (9) Nov 22, 2013
We detailed the across species conservation of molecular mechanisms involved in alternative splicings in the context of sex differences in our 1996 Hormones and Behavior review article: http://www.hawaii...ion.html

"Small intranuclear proteins also participate in generating alternative splicing techniques of pre-mRNA and, by this mechanism, contribute to sexual differentiation in at least two species..." -- we started with sex differences in microbial yeasts.

Today we see how far behind us others remain: Widespread sex differences in gene expression and splicing in the adult human brain http://dx.doi.org...omms3771

This is after I have published 3 more review articles and a book chapter.

Since Haldane's idea about mutations was first put forth, there has never been any experimental support for it.

Stop your nonsense. Inform yourself!
RealScience
5 / 5 (3) Nov 22, 2013
We detailed the across species conservation of molecular mechanisms involved in alternative splicings


And how is that evidence that mutations are never selected for?

You also still haven't answered where variety in genes (as opposed to in expression of genes) comes from if mutations are never selected for. For example, how are there at least five different sickle versions of the beta-globin gene that confer an advantage in malaria-prone regions, plus at least one non-sickle-cell version that confers an advantage in non-malarial areas, if, as you claim, natural selection never selects for a mutation?
JVK
1 / 5 (9) Nov 22, 2013
I've told you before that you are not intelligent enough to grasp biological facts. Why do you keep coming at me with more evidence of that fact? If you think mutations are selected, provide an experiment based example to support what you think. Stop attempting to get me to respond to your nonsensical theories with experimental evidence, when you have none to offer.

"In the light of recent advances in the characterization of the β-globin cluster, we propose that the complex patterns of diversity observed in this genomic region arose from distinct functional constraints related with the intricate process of chromatin and protein interactions coordinating the differential expression of genes at the β-globin cluster during development." http://www.ncbi.n...3622298/

"Constraints" Get it? Distinct constraints? Distinct constraints on protein interactions? Coordinating differential expression? No, says the anonymous fool; it's mutations.

RealScience
5 / 5 (3) Nov 22, 2013
@JVK -
Even the article YOU cite supports that the sickle cell variants arose through mutation and confers malarial resistance "Mutations in the β-chain of human HbA are associated with ... sickle cell disease", "alleles, which are known to confer resistance to Plasmodium falciparum".

These are selected FOR in malarial areas "occur at the highest frequencies ... in endemic areas of malaria ", increasing until the chance of inheriting two copies outweighs the benefit of the increased chance of inheriting one copy.
RealScience
5 / 5 (3) Nov 22, 2013
-continued-

As for your insistence on a human-run experiment:

For the human genome that the article is about, an experiment such as the evolution of malarial resistance would take millions of subjects and tens of thousands of year, and would be highly unethical. The best place to observe NATURAL selection of mutations is in NATURE.

But since you continue to ignore the grand experiment in natural selection that nature has provided for us, and insist on human-run laboratory experiments, we have to turn to bacteria to get enough generations in. For example, the following experiment supports that both preexisting variations and de novo mutations can be selected for:
http://www.plospa....1002158

JVK
1 / 5 (9) Nov 22, 2013
I am not insisting on human run experiments; the idea is ridiculous. I'm asking for experimental evidence that supports mutation-initiated natural selection. You misrepresent the findings from the sickle cell study, and infer that de novo mutations are responsible for antibiotic resistance which is, like the induction of changes in hemoglobin, an immune response required to maintain the epistasis of thermodynamically controlled organism-evel thermoregulation.

Whoever taught you to believe in the nonsense that you obviously believe in should be removed from whatever position allowed the nonsense to be taught. You should request a tuition refund and abandon all hope of pursuing a career in science, and drop the anonymity of your ridiculous "RealScience" moniker. Maintain your anonymity if you wish, but use "ReallyStupid" instead.

http://youtu.be/DbH_Rj9U524
JVK
1 / 5 (9) Nov 22, 2013
"In the light of recent advances in the characterization of the β-globin cluster, we propose that the complex patterns of diversity observed in this genomic region arose from distinct functional constraints related with the intricate process of chromatin and protein interactions coordinating the differential expression of genes at the β-globin cluster during development."

Does that sound like mutations are involved to anyone else? Multiple RNA transcript variants are produced by a gene thought to be involved with the regulation of beta-globin gene expression. Key regulatory proteins called transcription factors bind to the HBBP1 gene and the DNA surrounding the gene had all the telltale epigenetic marks of highly functional actively transcribed DNA. Also the data showed the HBBP1 gene was expressed in at least 251 different human cell and/or tissue types.

How could a mutated gene show up in 251 cell types and be maintained in the genome as a disease-related variant? Just in case?

RealScience
5 / 5 (3) Nov 22, 2013
I am not insisting on human run experiments; the idea is ridiculous.

After I gave you a natural example, you said
provide an experiment based example

What were you expecting, an experiment run by chimpanzees?
Or did you fail to understand what 'a human-run experiment' means?

As for you claim that I misrepresent your β-globin reference:
Are you claiming that the paper doesn't support that the variety of sickle-cell genes arose through mutations?
Or are you claiming that the paper doesn't support that these mutations provide malarial resistance?
Or are you claiming that the paper doesn't support that these mutations are prevalent in areas where malaria is endemic?
RealScience
5 / 5 (3) Nov 22, 2013
Does that sound like mutations are involved to anyone else?

It sounded to the authors of the paper like the variation in the β-globin genes came from mutations: "Mutations in the β-chain of human HbA..."

It also sounds like it to the authors of http://www.nature...-8756219
Note the bold sub-heading: "Mutant Beta-globin Leads to Positive Natural Selection".

Open your eyes. Of course nutrition plays a role (as do even your beloved pheromones), but mutations also play a role. Mutations occur, so why wouldn't nature make use of them?
JVK
1 / 5 (9) Nov 22, 2013
As I said, no experimental evidence suggests that mutations are fixed in the genome. You ask "...why wouldn't nature make use of them?" I'm asking how would nature make use of them. You infer it just happens.

If I could summarize what you seem to believe, it is that mutations arise and are not fixed in the genome but are still somehow selected for something that may somehow benefit an organism and that benefit will somehow increase the numbers of that type of organism in a given population in a given ecological niche.

I'm saying that adaptive evolution is nutrient-dependent and pheromone-controlled in species from microbes to man, which is exactly what all experimental evidence shows in every species tested, and I have published a series of detailed review articles with examples from across species.

I'm not saying you're wrong, however. I'm just asking for experimental evidence that you think shows you are right. Not my evidence; yours.

JVK
1 / 5 (9) Nov 23, 2013
"Genetically altered mice are a powerful experimental tool, but the extent to which recent positive selection in humans acts on pathways and amino-acid residues that have been conserved across mammalian evolution is uncertain." http://dx.doi.org.../495325a

"...natural selection is an evolutionary process initiated by mutation. It does not have any creative power in contrast to the statements made by some authors." http://www.amazon...99661731

Genetically altered mice and experimental evidence from every other model organism shows that nutrients are naturally selected so that organisms do not starve to death, and that pheromones control the physiology of reproduction. The creative power of nutrients is that they epigenetically effect alternative splicings, amino acid substitutions, and stochastic gene expression, which enables the creation of new species with behavior controlled by the metabolism of nutrients to species specific pheromones via conserved mechanisms.
RealScience
5 / 5 (3) Nov 23, 2013
@JVK - you said:
Mutation-initiated natural selection seems to be fading away into the obscurity of a flawed paradigm never supported by experimental evidence.

I pointed out that the article you were commenting on was on a class of mutations that had been selected FOR in natural selection, and that nature was the best place to look for such evidence.

I then pointed out the example of an experiment that nature has been running for tens of thousands of generation on millions of subject, in which natural selection has selected FOR mutations. You STILL haven't replied as to where the variation in GENES comes from if not from mutation, and even the article you referenced ascribed that variation to mutation.

Since you seem to trust a small-scale approximation of natural selection more than the real thing, I then pointed out an example of mutations being selected FOR in a human-run laboratory experiment.

What part of the evidence have you failed to understand?

RealScience
5 / 5 (3) Nov 23, 2013
"...why wouldn't nature make use of them?" I'm asking how would nature make use of them.

The sickle-cell anemia case is an example of how nature DOES make use of mutations.

It is also an example of how:
mutations arise and are not fixed in the genome but are still somehow selected for something that may somehow benefit an organism and that benefit will somehow increase the numbers of that type of organism in a given population in a given ecological niche


What part of the example did you fail to understand?

(Even the paper YOU referenced ascribes the variation in gene sequences to mutation, that some variants provide malarial resistance, and that these variant are most common in areas where malaria is endemic.)

RealScience
5 / 5 (3) Nov 23, 2013
Regarding:
...natural selection is an evolutionary process initiated by mutation. It does not have any creative power in contrast to the statements made by some authors."


Your link didn't work, but the reference is from "Mutation-Driven Evolution" by Masatoshi Nei.

Let's look at the context of the quoted passage. The paragraph that you quote from says:
"Natural selection is for saving advantageous mutations and eliminating harmful mutations... therefore natural selection is an evolutionary process initiated by mutation. It does not have any creative power in contrast to the statements made by some authors."


Again your own reference goes AGAINST your claim that "Mutation-initiated natural selection seems to be fading away" and supports my position that mutations can be selected FOR by natural selection.

So what part of your own reference did you fail to understand this time?

JVK
1 / 5 (9) Nov 23, 2013
"Reproductive isolation evidently can arise with little or no morphological differentiation."
JVK
1 / 5 (9) Nov 23, 2013
1973: "Reproductive isolation evidently can arise with little or no morphological differentiation."

1973: "alpha chains of hemoglobin have identical sequences of amino acids in man and the chimpanzee, but they differ in a single amino acid (out of 141) in the gorilla."

1973: "The remarkable advances of molecular biology in recent years have made it possible to understand how it is that diverse organisms are constructed from such monotonously similar materials: proteins composed of only 20 kinds of amino acids and coded only by DNA and RNA, each with only four kinds of nucleotides."

http://img.signal...nsky.pdf

What part of "an anonymous fool who has learned nothing about the cause of adaptions in the past 4 decades do you not understand?" Adaptations are nutrient-driven and pheromone-controlled!

James V. Kohl, founder: Pheromones.com http://pheromones.com/
RealScience
5 / 5 (3) Nov 23, 2013
@JVK - What do any of these have to do with whether mutations are sometimes selected for?

"Reproductive isolation evidently can arise with little or no morphological differentiation."

As I pointed out last time you tried that quote:
@JVK - lack of morphological differentiation does not imply lack of differentiation.

You failed to refute or even respond to that point back in January (http://phys.org/n...s.html).

As for little variation in the alpha chains of hemoglobin, the variations being discussed are in the BETA chain.

And not only does your "remarkable advances" quote fail to imply that mutations are never selected for, but the reference itself supports my point.

- continued -
RealScience
5 / 5 (4) Nov 23, 2013
Here is a quote from the "remarkable advances" reference that you cited:

Much work has been done in recent years on individual variations in amino acid sequences of hemoglobins of human blood. More than 100 variants have been detected. Most of them involve substitutions of single amino acids-substitutions that have arisen by genetic mutations in the persons in whom they are discovered or in their ancestors. As expected, some of these mutations are deleterious to their carriers, but others apparently are neutral or even favorable in certain environments.
(http://www.pbs.or...1.html).

So again your own reference supports that hemoglobin variations arise through mutation and that some such variations are favorable.
Did you fail to understand yet another of your own references?
JVK
1 / 5 (9) Nov 23, 2013
You can't recognize the difference between someone saying that mutations arise and attributing that obvious fact to their role as the initiators of natural selection.

If you do not agree that "adaptations are nutrient-driven and pheromone-controlled" sans mutations, offer experimental evidence that supports whatever nonsense you do believe. Or, simply state what you believe so that others can recognize that it is nonsense. For example, the belief in mutation-initiated natural selection is experimentally unsubstantiated nonsense. So tell us; "I believe in that" or provide experimental evidence that supports whatever you do believe in.
Zephir_fan
Nov 23, 2013
This comment has been removed by a moderator.
Zephir_fan
Nov 23, 2013
This comment has been removed by a moderator.
Zephir_fan
Nov 23, 2013
This comment has been removed by a moderator.
RealScience
5 / 5 (2) Nov 23, 2013
You can't recognize the difference between someone saying that mutations arise and attributing that obvious fact to their role as the initiators of natural selection.
...
the belief in mutation-initiated natural selection is experimentally unsubstantiated nonsense.


Wow, not only do you either fail to read or fail to comprehend the articles that you quote from, but now it appears that you even fail to even read what you quote.
Remember your quote from Masatoshi Nei's "Mutation-Driven Evolution"? I'll copy the first half straight from your post:
...natural selection is an evolutionary process initiated by mutation.

So your own quote disagrees with you.
JVK
1 / 5 (9) Nov 23, 2013
Evidence for Ecological Speciation and Its Alternative http://www.scienc...abstract

Excerpt: ...has accumulated from top-down studies of adaptation and reproductive isolation [reviewed in (2, 8, 9)]. The alternative is "....mutation-order speciation, divergence occurs when different mutations arise and are fixed in separate populations adapting to similar selection pressures."

No experimental evidence suggests any mutations that arise are ever fixed in the DNA of organized genomes in any species from microbes to man. That fact was clearly stated in An experimental test on the probability of extinction of new genetic variants. http://www.nature...417.html

Species-specific pheromones have always been most closely linked to reproductive isolation, which is exemplified by the role they play in the nematodes that showed mutations are not fixed in their genome.

Tell us about what you believe, not why I'm wrong!
RealScience
5 / 5 (2) Nov 23, 2013
Tell us about what you believe, not why I'm wrong!


I believe that mutations create variations in genes (and in other DNA regions, and in heritable epigenetic markings, but that's beside the point).
I believe that natural selection acts on these variations.
I believe that in some cases natural selection selects for a mutation.
My understanding is that you accept the first two, but disagree with the last one.
Is my understanding of your position correct?

JVK
1 / 5 (9) Nov 23, 2013
Thanks. I have seen no experimental evidence that supports any aspect of mutation-initiated natural selection or mutation-driven evolution. Neither have you, because there is none. Thus, your beliefs are based on nothing -- except what you may have been taught by others who believed the same things for the same reasons. I believe the experimental evidence of cause and effect in the context of my well-detailed model of conserved molecular mechanisms in species from microbes to man.

Blind faith in theory defies scientific progress, which requires the comparison of two testable hypotheses in cases where one hypothesis is supported by experimental evidence and the other is not -- or one is not supported by enough evidence to scientifically establish its explanatory power. Your faith in theory defies the common sense approach to life that is nutrient-dependent, and species diversity that is pheromone-controlled.

Kind regards to you and others who keep the faith (e.g, in nonsense),

JVK

Zephir_fan
Nov 23, 2013
This comment has been removed by a moderator.
RealScience
5 / 5 (2) Nov 24, 2013
I have seen no experimental evidence that supports any aspect of mutation-initiated natural selection or mutation-driven evolution.


First, there is plenty of evidence that it happens in nature (the sickle-cell mutations are a well documented case) so my beliefs are based on the results of ACTUAL natural selection, and are thus far from 'blind faith'.

Second, since you seem to value imitations more than reality, I sent you a link to a laboratory experiment documenting selection for de novo mutations, so if you have seen no experimental evidence then you either didn't read it or didn't comprehend it.

Now do you still stand by your earlier statement that:
"No evidence suggests natural selection operates on mutations to cause adaptive evolution"?
If so, then it is your faith that is blind, for then you hold it in spite of evidence to the contrary, including the papers that you yourself referred to.
JVK
1 / 5 (9) Nov 24, 2013
"Scientists are exploring how organisms can evolve elaborate structures without Darwinian selection."

"Others maintain that as random mutations arise, complexity emerges as a side effect, even without natural selection to help it along. Complexity, they say, is not purely the result of millions of years of fine-tuning through natural selection—the process that Richard Dawkins famously dubbed "the blind watchmaker." To some extent, it just happens."

http://www.scient...20130722

It is obvious that virtually no intelligent people believe in natural selection. Thus, everyone must conclude that "RealScience" is not that bright, and does not realize it.

Zephir_fan
Nov 24, 2013
This comment has been removed by a moderator.
RealScience
5 / 5 (3) Nov 24, 2013
@JVK - Almost everyone in the fields of genetics supports a role for mutation being selected for as a contributing factor in evolution. I suppose you claim that none of them are intelligent.

And as I pointed out above, even the references you cited supported a role for mutations in natural selection. If you think that those authors aren't that bright, then why did you cite their works? Gotcha!

As I pointed out back in January, all of your insults so far actually apply to yourself - what do you do - look in a mirror to come up with them?

And you still haven't answered whether you still hold that "No evidence suggests natural selection operates on mutations to cause adaptive evolution"?

Nor have you answered when the variety in the genes themselves comes from if not from mutations.

I answered you, so stop dodging these questions.
RealScience
5 / 5 (2) Nov 24, 2013
why don't you peddle your perfume somewhere else and let the smart people try to teach you something.


@Zephir_fan -
JVK doesn't want to learn anything that conflicts with what he holds most dear.
He knows that to acknowledge mutations ever being selected for is to acknowledge that mutations plus natural selection can add information to the genome, and that would destroy the linch-pin of his argument that a divine power must have put the information there. Or at least so understand from previous exchanges with him.

Why he insists that his god can't use mutations is beyond me. We mere humans use mutations for creativity in genetic algorithms in computers, so it clearly can be done. And it is much smarter to have a process that evolves variety than to have to create every detail oneself, so he is basically insulting his own god by demanding that his god not to use smart tools.
JVK
1 / 5 (9) Nov 25, 2013
How does mutation-initiated natural selection work sans fixation of the mutation(s)?

http://www.scienc...5804.htm

NOTES: genetic diversity could be maintained indefinitely, without one allele or the other ever being fixed in the population. Our data suggests that the value a new allele brings to the individuals is not fixed. Populations are dynamic and complex with plenty of interactions between individuals and between these and the environment. Initial stages when the new alleles appear cannot tell us what the effects of the alleles will be a few generations later, when the population has already changed." To our knowledge, this is the first time anyone was able to directly test Haldane's theory. We have proved it correct for the initial stages, when a new allele appears in a population. But our results show that further empirical work and more theoretical models are required to accurately predict the fate of that allele over long time spans.
JVK
1 / 5 (9) Nov 25, 2013
@JVK -And as I pointed out above, even the references you cited supported a role for mutations in natural selection. If you think that those authors aren't that bright, then why did you cite their works? Gotcha!


I tried repeatedly to address your misrepresentations of the works I have cited. You don't get it! There is more to consider that just whether mutations occur or whether natural selection occurs. Natural selection must occur for something associated with the mutation(s), and no experimental evidence suggests that is even a remote possibility, especially since mutations are not fixed in the organized genome of any species. For contrast, all experimental evidence shows that adaptive evolution occurs via ecological, social, neurogenic, and socio-cognitive niche construction, which is nutrient-dependent and pheromone-controlled (sans mutations). Selection of nutrients enables controlled niche construction associated with de novo creation of olfactory receptor genes.
Zephir_fan
Nov 25, 2013
This comment has been removed by a moderator.
JVK
1 / 5 (9) Nov 25, 2013
They include the information on the open access article as is typical of such reporting. You can verify their interpretation or quotes, if you are intelligent enough to click on the link or find the article some other way.

Ivo M. Chelo, Judit Nédli, Isabel Gordo & Henrique Teotónio. An experimental test on the probability of extinction of new genetic variants. Nature Communications, September 2013 DOI: 10.1038/ncommsS3417

http://www.nature...417.html

Abstract: "In 1927, J.B.S. Haldane reasoned that the probability of fixation of new beneficial alleles is twice their fitness effect. This result, later generalized by M. Kimura, has since become the cornerstone of modern population genetics. There is no experimental test of Haldane's insight ...
Zephir_fan
Nov 25, 2013
This comment has been removed by a moderator.
JVK
1 / 5 (9) Nov 25, 2013
From Fertilization to Adult Sexual Behavior our 1996 Hormones and Behavior invited review
http://www.hawaii...ion.html

Human pheromones: integrating neuroendocrinology and ethology our award-winning 2001 Neuroendocrinology Letters review http://www.nel.ed...view.htm

The Mind's Eyes: Human pheromones, neuroscience, and male sexual preferences my 2006/7 award-winning monograph/book chapter http://www.sexarc...kohl.htm

Whatever intelligence you think you are displaying here is actually nearly the highest level of ignorance I have ever encountered from any anonymous fool.
Zephir_fan
Nov 25, 2013
This comment has been removed by a moderator.
JVK
1 / 5 (9) Nov 25, 2013
How did the two genes required for fertilization in the mouse mutate into existence?

Two Y Genes Can Replace the Entire Y Chromosome for Assisted Reproduction in the Mouse
http://www.scienc...abstract

It Takes Two
http://www.the-sc...kes-Two/

Current theory suggests that this sort of thing "just happens." And, many people seem to believe in that theory.

http://www.scient...20130722

"Others maintain that as random mutations arise, complexity emerges as a side effect, even without natural selection to help it along. Complexity, they say, is not purely the result of millions of years of fine-tuning through natural selection—the process that Richard Dawkins famously dubbed "the blind watchmaker." To some extent, it just happens."
RealScience
5 / 5 (2) Nov 25, 2013
Thank you for your recent responses - a civilized discussion is much more productive!

The Chelo et al paper that you cite shows that harmful alleles can persist and the beneficial alleles are not ALWAYS successful, and that in cases where the benefit is frequency-dependent then multiple alleles are typically maintained (as is the case with sickle-cell genes where one copy provides malarial resistance but two copies produce severe disease).

It also discusses the probability of fixation in the case where an allele is beneficial regardless of frequency, and shows the expected probability of fixation over 100 and 1000 generations. The expected probability of fixation is quite high even for a 15% benefit, although this experiment was not run long enough to confirm the model.

Thus your reference supports that fixation of beneficial alleles can occur with high probability (see graphs 2b and 4a), although it does not prove it.
RealScience
5 / 5 (2) Nov 25, 2013
@JVK - I don't disagree with your comments when your ascribe a role for nutrients and epigenetics in adaptation. In the short term (up to thousands or even tens of thousands year for humans) I believe that these dominate over mutations. Over the mid-term things like copy-number variations dominate; some would call these mutations, and others wouldn't.

However in the long term (hundreds of thousands to millions of generations), I think that mutations play an important role. Therefore I disagree with is what I UNDERSTAND to be your opinion that mutants in the genetic sequence itself are NEVER selected for by natural selection.

Is this or is this not a belief that you hold?
JVK
1 / 5 (9) Nov 25, 2013
You continue to look at only one side of the evidence, and it is the side that favors fixation of mutations despite no experimental evidence in any species that mutations are either fixed or that they can be somehow naturally selected. For contrast, nutrient-dependent pheromone-controlled amino acid substitutions have been linked to individual and species differences in organisms from microbes to man, which is what I modeled in "Nutrient-dependent/pheromone-controlled adaptive evolution: a model"

The fact that you either have not read this or do not understand it makes further comments from me a waste of time. My review shows that differences between grazing and predatory nematodes is caused by the nutrient-dependent rewiring of their primitive nervous system and pheormone-controlled physiology of reproduction. That's real science; it explains cause and effect via experimental evidence that fits what is known about conserved molecular mechanisms. You prefer a theory!
JVK
1 / 5 (9) Nov 25, 2013
"Francois Jacob even claimed that ''the probability that a functional protein would appear de novo by random association of amino acid is practically zero'' in a paper he published in 1976 (Jacob, 1977). The de novo origination of genes has occurred widely during evolution in viruses, prokaryotes, and eukaryotes.The proportion of new protein coding genes that originated de novo among all new genes that originated in human lineage is possible about 10%, a percentage similar to that seen in Drosophila."

http://www.scienc...13000705

The "practically zero" chance must be somehow linked to a mechanism by which the protein could be selected if it did arise and became fixed in the genome. No experimental evidence suggests this is possible. What you do not understand about cause and effect that enables your belief in a nonsensical theory?
Zephir_fan
Nov 25, 2013
This comment has been removed by a moderator.
RealScience
5 / 5 (2) Nov 25, 2013
"Francois Jacob even claimed that ''the probability that a functional protein would appear de novo by random association of amino acid is practically zero"


That the chance of a functional protein appearing by random association of amino acids is small has little to do with whether mutations can alter existing genes in a way that benefits the organism.

A common change in the genetic code is the addition of a copy of a gene, whether through genome duplication, chromosome duplication, copy-number variation or copying error. Although most such alterations are harmful, homeostasis is powerful enough to mitigate some to allow them to persist for generations. And once a duplicate gene is present, then a mutation does not have to create a functional protein from scratch, but merely by altering an already-functional protein.

So do you believe that natural selection NEVER selects for a mutation?
JVK
1 / 5 (9) Nov 25, 2013
I'm not willing to believe that natural selection ever selects for a mutation, since there is no experimental evidence that suggests that is possible even if there was evidence that mutations are fixed in the DNA of the organized genome of any species. But, how can you not understand that the issues here are not a matter of belief? The entirety of the discussion I've been trying to have involves an evidence-based approach to finding experimental support for different hypotheses. You seem to think that nutrient-dependent pheromone controlled amino acid substitution is the null hypothesis, when it is clearly exemplified by experimental evidence across species via conserved molecular mechanisms. You should long ago have grasped the fact that mutation-initiated natural selection is the null hypothesis and it is not supported by any experimental evidence whatsoever -- and it never has been.
RealScience
5 / 5 (2) Nov 25, 2013
how can you not understand that the issues here are not a matter of belief

I am using the term that you introduced. If you had asked what my opinion was, rather than what I believe, I would have likewise asked for you opinion.

I'm not willing to believe that natural selection ever selects for a mutation, since there is no experimental evidence that suggests that is possible


But I sent you a link to an experiment that demonstrated de novo mutations being selected for: http://www.plospa....1002158

And a 10,000 generation experiment already showed just that ~20 years ago:
www.pnas.org/cont...l.pdf‎

So natural selection FOR mutations IS shown in experiments.

More importantly it is ALSO shown in nature itself by evidence such as the distribution of malaria-resistance alleles (e.g., http://www.nature...756219).
JVK
1 / 5 (9) Nov 25, 2013
What you think exemplifies selection for de novo mutations does nothing of the kind. If true examples, there would be no reason for theoretical biologists to extract physics from mutation-driven evolution. The biophysical constraints on mutations is why they cannot be selected. They perturb the required thermodynamics of intercellular signaling that enables organism-level thermoregulation and the epistasis required for speciation. You are looking at all this from such a low level of scientific understanding that it is like trying to teach a small child about conserved molecular mechanisms involving physics, chemistry, the basic principles of biology, and levels of biological organization required for species diversity. Add to that the fact you are unwilling to read my published works on alternative splicings, stochastic gene expression et al with examples from species from microbes to man and what we have here is a communications breakdown. You simply say 'Nuh-uh' no matter what I say!
Zephir_fan
Nov 25, 2013
This comment has been removed by a moderator.
RealScience
5 / 5 (2) Nov 25, 2013
What you think exemplifies selection for de novo mutations does nothing of the kind.

The authors of the papers I cited thought that the experiments exemplify selection for de novo mutations, and the real-world malarial example has numerous papers saying the same thing.

The biophysical constraints on mutations is why they cannot be selected. They perturb the required thermodynamics of intercellular signaling that enables organism-level thermoregulation and the epistasis required for speciation.


As even you have acknowledged, mutations do occur so they obviously do not violate any principles of thermodynamics. And for any beneficial mutations, their selection does not either.
Are you claiming that no mutation can ever be beneficial?

In any case, both the natural and human experiments I have cited show mutations being selected for, and the reality that something actually exists trumps a model that says that it can't exist.

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