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Author Topic:   The origin of new alleles
crashfrog
Member (Idle past 1497 days)
Posts: 19762
From: Silver Spring, MD
Joined: 03-20-2003


Message 46 of 92 (381359)
01-30-2007 6:19 PM
Reply to: Message 44 by Hawks
01-30-2007 5:04 PM


Re: The origin of new alleles
I fail to see why that would be a difference.
1) We're not talking about functional sequences that are crucial to tsetse flies.
2) They're not specific to tsetse flies or humans.
In other words, I don't see a reason to call them "tsetse fly genes"; there may be endogenous retrotransposons that are homologous between humans and flies such as the tsetse, but that's not at all the same thing.
But in the end both x and y carry the same gene, so I'm not sure why your objection would matter.
Are we even talking about genes, though? Or just transposable elements? They're degraded beyond all functioning, and are nothing more than introns in eukaryotes, anyway.
I don't find it too implausible that a gene from a fly was transferred to an invasive bacterium that later invaded a human cell that subsequently took up some bacterial DNA
Not just any cell; a human gamete that then happened to be the one in a million sperm that impregnanted a mate.
I find it physiologically implausible, I guess. There are physical barriers and protections between sperm and the rest of the body - mostly to keep the sperm protected from the male's own immune system.
It doesn't have to just get into a cell; it has to get into a germline cell, and I don't see anybody saying how that happens without a lot of handwaving. I'm just skeptical, is all, that horizontal gene transfer can be that common in metazoan life.

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 Message 44 by Hawks, posted 01-30-2007 5:04 PM Hawks has replied

Replies to this message:
 Message 50 by Hawks, posted 01-30-2007 10:41 PM crashfrog has replied

  
Fosdick 
Suspended Member (Idle past 5530 days)
Posts: 1793
From: Upper Slobovia
Joined: 12-11-2006


Message 47 of 92 (381372)
01-30-2007 7:17 PM
Reply to: Message 44 by Hawks
01-30-2007 5:04 PM


Re: The origin of new alleles
So, Hoot Mon's link and claim that DNA has been transferred between humans and tse-tse's doesn't seem all too farfetched.
Now I just have to try to figure out why this is actually important for this thread.
I think horizontal genetic mobility connects to this topic relevantly, because lateral DNA transfer may be associated with the origin of new alleles. It may also associate with their durability and transposability once they become new alleles.
”Hoot

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Fosdick 
Suspended Member (Idle past 5530 days)
Posts: 1793
From: Upper Slobovia
Joined: 12-11-2006


Message 48 of 92 (381379)
01-30-2007 7:37 PM
Reply to: Message 43 by crashfrog
01-30-2007 4:47 PM


Re: The origin of new alleles
I don't see how it works in sexual metazoans.
For instance, a biting fly pierces my skin and begins to feed off my blood. How does any of it's genes get from the cells of its digestive tract (the only cells currently in contact with my body) all the way down to the protected gametes in my genitals? And I'm male. How would it work in my wife, who at birth had already generated all the gametes she'll ever have? Meiosis is over by the time she could possibly be exposed to these parasites.
These are good questions. The answers are not so easiliy summarized, but I'm serious about Frederic Bushman's book, referenced upthread. He brings forward a great deal research about such topics (chapter titles) as: "A transposon progenator of the vertebrate immune system," "Lateral DNA transfer and the AIDS epidemic," "Genes floating in a sea of retrotransposons," "Controlling mobile element activity," and "Lateral DNA transfer: Themes and evolutionarey implications." I think you would find answers to your questions in this book. (I found it so important I purchased a copy for myself.)
”Hoot

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 Message 43 by crashfrog, posted 01-30-2007 4:47 PM crashfrog has replied

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crashfrog
Member (Idle past 1497 days)
Posts: 19762
From: Silver Spring, MD
Joined: 03-20-2003


Message 49 of 92 (381388)
01-30-2007 8:10 PM
Reply to: Message 48 by Fosdick
01-30-2007 7:37 PM


Re: The origin of new alleles
Well, thanks for the recommendation - I don't even have a library card yet but I'll see if I can't find it.

This message is a reply to:
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Hawks
Member (Idle past 6176 days)
Posts: 41
Joined: 08-20-2006


Message 50 of 92 (381429)
01-30-2007 10:41 PM
Reply to: Message 46 by crashfrog
01-30-2007 6:19 PM


Re: The origin of new alleles
quote:
1) We're not talking about functional sequences that are crucial to tsetse flies.
2) They're not specific to tsetse flies or humans.
In other words, I don't see a reason to call them "tsetse fly genes"; there may be endogenous retrotransposons that are homologous between humans and flies such as the tsetse, but that's not at all the same thing.
You claimed earlier :"Moreover - the fact that some endogenous retrotransposon jumped from tsetse flies to humans (or vice-versa) is not the same as saying "humans carry around tsetse fly genes.". So it was a given that a piece of DNA got from a fly into humans. Whether or not this DNA was crucial to the fly is irrelevant.
The non-specificity of the genes to humans and flies might, as I also pointed out in an earlier post, be relevant. BUT it was already a given that the DNA had transferred from a fly into a human - and so, in this instance, it is irrelevant.
quote:
Are we even talking about genes, though? Or just transposable elements? They're degraded beyond all functioning, and are nothing more than introns in eukaryotes, anyway.
Mariner elements do contain genes. These were at least (well probably anyway) functional at the time of transposition.
quote:
I find it physiologically implausible, I guess. There are physical barriers and protections between sperm and the rest of the body - mostly to keep the sperm protected from the male's own immune system.
It doesn't have to just get into a cell; it has to get into a germline cell, and I don't see anybody saying how that happens without a lot of handwaving. I'm just skeptical, is all, that horizontal gene transfer can be that common in metazoan life.
I very much doubt that it would be a common occurrence. But there are no absolute barriers against it either. As I already stated, DNA can migrate into the nucleus of a eukaryotic cell. Free DNA can be longlived inside a human - mothers can carry around their childrens DNA in themselves for years after birth (it probably crossed the placenta). Bacteria and viruses can aid in the transport of DNA into/out of eukaryotic cells. Transposons such as the mariner elements mentioned are "likely" to integrate into a genome (in that they contain the gene to do it and that the gene is not dependent on host-factors), should the find themselves in the right spot. I suppose that lack of direct observation might be called hand-waving but there are mechanisms that can do it.

This message is a reply to:
 Message 46 by crashfrog, posted 01-30-2007 6:19 PM crashfrog has replied

Replies to this message:
 Message 51 by crashfrog, posted 01-31-2007 3:32 PM Hawks has replied

  
crashfrog
Member (Idle past 1497 days)
Posts: 19762
From: Silver Spring, MD
Joined: 03-20-2003


Message 51 of 92 (381513)
01-31-2007 3:32 PM
Reply to: Message 50 by Hawks
01-30-2007 10:41 PM


Re: The origin of new alleles
So it was a given that a piece of DNA got from a fly into humans.
Er, no, we don't. That's my point. There's no evidence that these are sequences from flies; only sequences homologous between these flies and humans.
These were at least (well probably anyway) functional at the time of transposition.
This is the sort of hand-waving I'm talking about when it comes to horizontal gene transfer between extremely complex, disparate organisms.
But there are no absolute barriers against it either.
I disagree. The barriers that seperate spermatozoa from the rest of the body are so tight they can screen out antibodies, which are much smaller than bacteria. How is your nomad bacterium supposed to get through that?
I suppose that lack of direct observation might be called hand-waving but there are mechanisms that can do it.
I'm still waiting to hear what those are.

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 Message 50 by Hawks, posted 01-30-2007 10:41 PM Hawks has replied

Replies to this message:
 Message 52 by Fosdick, posted 01-31-2007 7:33 PM crashfrog has replied
 Message 54 by Wounded King, posted 02-01-2007 12:33 PM crashfrog has not replied
 Message 61 by Hawks, posted 02-01-2007 10:07 PM crashfrog has replied

  
Fosdick 
Suspended Member (Idle past 5530 days)
Posts: 1793
From: Upper Slobovia
Joined: 12-11-2006


Message 52 of 92 (381599)
01-31-2007 7:33 PM
Reply to: Message 51 by crashfrog
01-31-2007 3:32 PM


Re: The origin of new alleles
Hawks wrote:
But there are no absolute barriers against it either.
crashfrog replies:
I disagree. The barriers that seperate spermatozoa from the rest of the body are so tight they can screen out antibodies, which are much smaller than bacteria. How is your nomad bacterium supposed to get through that?
I suppose that lack of direct observation might be called hand-waving but there are mechanisms that can do it.
I'm still waiting to hear what those are.
Are you saying that DNA transposons are incapable of moving between genomes of different species? There is abundant evidence for this, and mariner elements are the enablers. Isn't that what Barbara McClintock's work was all about? Indeed they ARE the mechanisms you keep questioning. How tsetse-fly genes eventually got into human germ cells to gain homological durability in the genome, I really couldn't say. The bloodstreams of humans circulate everwhere, including the gonads, and there is ample evidence that genes and transposons in fly saliva can enter the bloodstreams of other species.
”Hoot Mon

This message is a reply to:
 Message 51 by crashfrog, posted 01-31-2007 3:32 PM crashfrog has replied

Replies to this message:
 Message 53 by crashfrog, posted 02-01-2007 11:48 AM Fosdick has replied

  
crashfrog
Member (Idle past 1497 days)
Posts: 19762
From: Silver Spring, MD
Joined: 03-20-2003


Message 53 of 92 (381635)
02-01-2007 11:48 AM
Reply to: Message 52 by Fosdick
01-31-2007 7:33 PM


Re: The origin of new alleles
Are you saying that DNA transposons are incapable of moving between genomes of different species?
No, I'm saying that a DNA transposon that leaps into the genome of a skin cell, or a blood cell, or some other somatic cell doesn't get passed on to any other individuals.
The transposon would have to leap into a gamete, and I don't see that as physiologically likely, given how protected spermatocytes are from the rest of the body. They're basically in a little isolation ward of their own, to avoid an autoimunnological response from the male's own body, which doesn't recognize haploid sperm cells as its own.
Two arbitrary cells in close proximity? I don't have a problem with that. Sure, genetic sequences could easily leap between them under the proper circumstances.
But what possible circumstances could result in a DNA leap between the mouth of an insect and a sperm cell that, for all intents and purposes, might as well be on the other side of the planet? This is the part that horizontal gene transfer advocates gloss over. "Eh, it just happened." It's just highly unlikely to me, is all.

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 Message 52 by Fosdick, posted 01-31-2007 7:33 PM Fosdick has replied

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 Message 55 by Fosdick, posted 02-01-2007 12:37 PM crashfrog has replied

  
Wounded King
Member
Posts: 4149
From: Cincinnati, Ohio, USA
Joined: 04-09-2003


Message 54 of 92 (381640)
02-01-2007 12:33 PM
Reply to: Message 51 by crashfrog
01-31-2007 3:32 PM


Re: The origin of new alleles
I disagree. The barriers that seperate spermatozoa from the rest of the body are so tight they can screen out antibodies, which are much smaller than bacteria. How is your nomad bacterium supposed to get through that?
The infection need not occur during spermatogenesis or even in the sperm at all. Bacteria surviving in the womb environment or which can pass through the placenta, or even simply the relevant sequence of transposon DNA perhaps given the number of active transposase like enzymes around such as endogenous integrases, could affect an embryo at an early enough developmental stage to affect all or some of the germ line lineage.
TTFN,
WK

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Fosdick 
Suspended Member (Idle past 5530 days)
Posts: 1793
From: Upper Slobovia
Joined: 12-11-2006


Message 55 of 92 (381641)
02-01-2007 12:37 PM
Reply to: Message 53 by crashfrog
02-01-2007 11:48 AM


Re: The origin of new alleles
But what possible circumstances could result in a DNA leap between the mouth of an insect and a sperm cell that, for all intents and purposes, might as well be on the other side of the planet? This is the part that horizontal gene transfer advocates gloss over. "Eh, it just happened." It's just highly unlikely to me, is all.
You're knee-jerking again, frog. Your question is at least partially answered in my last post (#52):
quote:
Indeed they ARE the mechanisms you keep questioning. How tsetse-fly genes eventually got into human germ cells to gain homological durability in the genome, I really couldn't say. The bloodstreams of humans circulate everwhere, including the gonads, and there is ample evidence that genes and transposons in fly saliva can enter the bloodstreams of other species.
The bloostream is a river of opportunity for any blood-borne agent. The same bloodstream that circulates through your skin also circulates through your testicles (if you got 'em). I don't see why this is so difficult to grasp. Even if it is unlikely that a gene in the saliva of an insect can travel through the bloodstream all the way into a meiotic event, it is not impossible.
repeating your question:
But what possible circumstances could result in a DNA leap between the mouth of an insect and a sperm cell that, for all intents and purposes, might as well be on the other side of the planet?
What? "...other side of the planet?" Come on, frog, by your ridiclous analogy your skin covers a parking lot in Lincoln, NE, while your nuts are somewhere in the Australian outback. Not quite so. If you got a penicillin shot in your arm for a testicular infection I think the drug could get down there without having to travel around the world to do it.
”Hoot

This message is a reply to:
 Message 53 by crashfrog, posted 02-01-2007 11:48 AM crashfrog has replied

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 Message 56 by crashfrog, posted 02-01-2007 1:28 PM Fosdick has replied

  
crashfrog
Member (Idle past 1497 days)
Posts: 19762
From: Silver Spring, MD
Joined: 03-20-2003


Message 56 of 92 (381644)
02-01-2007 1:28 PM
Reply to: Message 55 by Fosdick
02-01-2007 12:37 PM


Re: The origin of new alleles
The same bloodstream that circulates through your skin also circulates through your testicles (if you got 'em). I don't see why this is so difficult to grasp.
And what I'm telling you is that, like in the brain, there's a barrier between spermatozoa and the rest of the body, including the bloodstream. It's such a tight barrier that it can keep out your own body's antibodies. (And an antibody is a lot smaller than a bacteria, or even a free-floating transposon.)
Why is that so difficult to grasp?
AbE: I shouldn't say "like in the brain", because the barrier is actually very different, but it's there to screen out an autoimmunological response from the body, and to do so it has to be capable of screening out some very small things. Smaller than a free-floating endogenous retrotransposon.
Edited by crashfrog, : No reason given.

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 Message 57 by Fosdick, posted 02-01-2007 2:19 PM crashfrog has replied

  
Fosdick 
Suspended Member (Idle past 5530 days)
Posts: 1793
From: Upper Slobovia
Joined: 12-11-2006


Message 57 of 92 (381657)
02-01-2007 2:19 PM
Reply to: Message 56 by crashfrog
02-01-2007 1:28 PM


Re: The origin of new alleles
crashfrog, your barrier hypothesis is good. But what if the barrier fails for some reason? Things do jump barriers, you know. When any fly injects its saliva into the bloodstream of its host there could be a considerable amount of fly DNA that comes along with it each time. Do you deny this? Maybe your barrier is good most of the time, but maybe, just maybe, once in a while things don't work right and fly DNA jumps over the barrier and into a spermartozoan. What's impossible about that?
”Hoot

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 Message 56 by crashfrog, posted 02-01-2007 1:28 PM crashfrog has replied

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crashfrog
Member (Idle past 1497 days)
Posts: 19762
From: Silver Spring, MD
Joined: 03-20-2003


Message 58 of 92 (381663)
02-01-2007 2:55 PM
Reply to: Message 57 by Fosdick
02-01-2007 2:19 PM


Re: The origin of new alleles
But what if the barrier fails for some reason?
We know that when sperm come into contact with the rest of the body, it triggers an autoimmune response that tends to destroy the sperm and leave the male infertile.
Maybe your barrier is good most of the time, but maybe, just maybe, once in a while things don't work right and fly DNA jumps over the barrier and into a spermartozoan.
Ok, so it's the one in a million occurance where free-floating DNA makes it all the way to the genitals, past a trillion other cells that it ignores before it finds a sperm, and then it's the one in a million chance this happens but the male is not rendered sterile by the autoimmune response circumventing the nurse cells, and then that one sperm is the one in ten million sperm that fertilizes an ovum.
At what point is the unlikelihood of this occurance greater than the total number of human males who have ever lived? And are these genes purported to be universal in the human genome? So we're talking about this having to occur fairly early in human evolutionary history, which means we're talking about it happening to a fairly small population.
I'm trying really hard not to sound like a creationist, or something, but the improbabilities are really adding up; all the genetics researchers I know think this is an unlikely possibility to say the least, and horizontal gene transfer advocates have a marked propensity towards overstating their claims, calling it "a new paradigm in biology" and other phrases that look great on posters and grant proposals, but might be just a tad hyperbolic.
It makes me distrustful, especially when conclusive evidence doesn't seem to be forthcoming.
I offer the following paper not to dismiss the entire phenomenon nor to paint HGT's proponents as universally mendacious liars, but simply one small example of how there maybe be generally simpler and more parsimonious explanations for unexpected genetic homologies between unrelated species:
No webpage found at provided URL: http://www.cbcb.umd.edu/~salzberg/docs/ScienceLateralTransfer.pdf
quote:
The human genome was analyzed for evidence that genes had been laterally
transferred into the genome from prokaryotic organisms. Protein sequence
comparisons of the proteomes of human, fruit y, nematode worm, yeast,
mustard weed, eukaryotic parasites, and all completed prokaryote genomes
were performed, and all genes shared between human and each of the other
groups of organisms were collected. About 40 genes were found to be exclusively
shared by humans and bacteria and are candidate examples of horizontal
transfer from bacteria to vertebrates. Gene loss combined with sample size
effects and evolutionary rate variation provide an alternative, more biologically
plausible explanation.

This message is a reply to:
 Message 57 by Fosdick, posted 02-01-2007 2:19 PM Fosdick has replied

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 Message 59 by Fosdick, posted 02-01-2007 3:52 PM crashfrog has replied

  
Fosdick 
Suspended Member (Idle past 5530 days)
Posts: 1793
From: Upper Slobovia
Joined: 12-11-2006


Message 59 of 92 (381680)
02-01-2007 3:52 PM
Reply to: Message 58 by crashfrog
02-01-2007 2:55 PM


Re: The origin of new alleles
Hmm. I'm not sure what point you are trying to make here. Your referenced article does indeed account for lateral DNA transfer. But it only addresses lateral transfer between prokaryotes and humans. It does NOT address lateral transfer between eukaryotes and humans. That happens, you know. To wit: From Frederic Bushman’s Lateral DNA Transfer/Mechanisms and Consequences (2002):
quote:
Our own DNA is a complex composite of imported sequences and mobile genetic parasites, and the dynamic remodeling of our genome continues to this day . What is not well known is that the DNA composition of organisms can be remarkably fluid. Surprisingly often, DNA is transferred from one organism to another, and that DNA can become stably incorporated in the recipient, permanently changing its genetic composition.

This message is a reply to:
 Message 58 by crashfrog, posted 02-01-2007 2:55 PM crashfrog has replied

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 Message 60 by crashfrog, posted 02-01-2007 4:10 PM Fosdick has replied

  
crashfrog
Member (Idle past 1497 days)
Posts: 19762
From: Silver Spring, MD
Joined: 03-20-2003


Message 60 of 92 (381684)
02-01-2007 4:10 PM
Reply to: Message 59 by Fosdick
02-01-2007 3:52 PM


Re: The origin of new alleles
Hmm. I'm not sure what point you are trying to make here.
I'm sorry, I thought my point was abundantly clear. It's simply that when we find unexpected homologies between unrelated organisms of considerable phylogenetic separation, HGT shouldn't be the immediate conclusion without some corroborating evidence.

This message is a reply to:
 Message 59 by Fosdick, posted 02-01-2007 3:52 PM Fosdick has replied

Replies to this message:
 Message 66 by Fosdick, posted 02-03-2007 7:50 PM crashfrog has replied

  
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