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Author
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Topic: Pseudogenes- Embargoed by Nature?
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Cre8ionist
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Member # 140
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posted 09. May 2003 09:18
The article I want to point to (Embargoed by Nature ) highlights an article published in the May 1, 2003 issue of the journal Nature. It starts off quote:
The mantra of molecular biology - DNA makes RNA, which makes protein* - has pretty much ignored pseudogenes.
and ends with
quote:
In continuing studies, the researchers hope to show the pseudogene-gene interaction is a general mechanism taking place in many cellular interactions.
The long and short of the article: Japanese researchers have discovered that pseudogenes are not useless.
Application to ID:
It has long been argued by Darwinists that pseudogenes are evidence against an "intelligent" designer. This argument can now go the way of the vestigial organ, biogenetic law, peppered moth, chimp/human %98 DNA similarity, reptile to bird transition, lightspeed can't decrease arguments. In other words, this argument will soon join the other "Icons of Evolution" in the "Science is Self-Correcting" file.
I remember reading in DBB the following quote from Kenneth Miller:
quote:
The theory of intelligent design cannot explain the presence of nonfuntional pseudogenes unless it is willing to allow that the designer made serious errors, wasting millions of bases of DNA on a blue print full of junk and scribbles. Evolution, in contrast, can easily explain them as nothing more than failed experiments in a random process of gene duplication that persist in the genome as evolutionary remnants.
I wonder if he'll print any sort of retraction, unfortunately, the more likely scenario is that the pseudoscientific argument of the absolute uselessness of pseudogenes will continue to be propagated for sometime just as the other arguments on the other icons did.....................................Cre8
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Josh
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posted 09. May 2003 10:46
Cre8
Great Article Spot!!! This is the post I made at the ASA email listserve when the paper came out a while ago, followed by the news and views published in the same journal.
Pseudogenes: Molecular Fossils or Functional Elements?
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Uh oh! Pseudogenes with a function! This discovery casts another doubt on
our list of solid evolutionary "proofs." See the following commentary on a
Nature article.
Maybe genomes aren't simply littered wastelands of evolutionary byproducts,
but are composed largely of important elements that contribute to the
purposeful generation of organisms? Ridiculous idea, to be sure. I have
always found arguments concerning the sloppiness of design in biology to be
extremely inept for supporting evolution. If you have billions of years of
evolutionary processes to work on refining something through random mutation
and natural selection, waste should be eliminated not accrued. At the same
time, it remains an open question as to how much function and purpose all
elements of the genome have in terms of biological activity. But of course,
for the adamant evolutionist, even if pseudogenes aren't molecular fossils,
the function they retain simply shows us the creativity of evolutionary
processes, right? Thus can any evidence negate/ bring question to the
veracity of evolution? This article characterizes the whole scenario as a
product of evolution despite the fact that the finding challenges the
long-held belief that pseudogenes are waste products of evolution. Now they
aren't necessarily waste, but we *know* that they are still byproducts of
evolution. Provocative finding indeed!!
Molecular biology: Complicity of gene and pseudogene
JEANNIE T. LEE
Jeannie T. Lee is at the Howard Hughes Medical Institute, Department of
Molecular Biology, Massachusetts General Hospital, and the Department of
Genetics, Harvard Medical School, Boston, Massachusetts 02114, USA.
e-mail: lee@molbio.mgh.harvard.edu
'Pseudogenes' are produced from functional genes during evolution, and are
thought to be simply molecular fossils. The unexpected discovery of a
biological function for one pseudogene challenges that popular belief.
Pseudogenes are defective copies of functional genes that have accumulated
to an impressive number during mammalian evolution1. Dysfunctional in the
sense that they cannot be used as a template for producing a protein,
pseudogenes are in fact nearly as abundant as functional genes2, 3. Why have
mammals allowed their accumulation on so large a scale? One proposed answer
is that, although pseudogenes are often cast as evolutionary relics and a
nuisance to genomic analysis, the processes by which they arise are needed
to create whole gene families4, such as those involved in immunity and
smell. But are pseudogenes themselves merely by-products of this process? Or
do the apparent evolutionary pressures to retain them hint at some hidden
biological function? For one particular pseudogene, the latter seems to be
true: elsewhere in this issue (page 91), Hirotsune and colleagues5 report
the unprecedented finding that the Makorin 1-p1 pseudogene performs a
specific biological task.
Hirotsune et al.5 had been analysing mice in which copies of a fruitfly gene
called Sex-lethal were randomly inserted in the mouse genome. In the course
of their studies, they encountered one mouse line that died shortly after
birth from multi-organ failure. As this occurred in only one mouse line out
of many, the results could not be explained by aberrant Sex-lethal
expression. Instead, the authors attributed their finding to a disruption of
the particular stretch of genomic information into which Sex-lethal had
inserted in this case. Whereas some might have dismissed the line as an
aberration and unworthy of the effort required to characterize it, Hirotsune
and colleagues delved deeper and were rewarded with the surprising finding
that a pseudogene can regulate the expression of the functional gene from
which it arose.
The authors first found that, in the mouse line in question, the inserted
Sex-lethal gene disrupted Makorin1-p1 — a pseudogene copy of the functional
Makorin1 gene. Only recently identified6, Makorin1 is an ancient gene that
has been evolutionarily conserved from nematode worms to fruitflies and
mammals, and encodes a putative RNA-binding protein. It is the prototype of
a large family of Makorin genes and pseudogenes, and is located on mouse
chromosome 6.
By contrast, Hirotsune et al. found that the pseudogene Makorin1-p1 lies on
chromosome 5. Like the original gene, this pseudogene can be 'transcribed'
into a messenger RNA copy. But it has incurred mutations during evolution,
so the mRNA cannot, as is usual, be used to produce a protein. Further
differences between the gene and pseudogene include the fact that the
Makorin1-p1 mRNA contains only the first (that is, 5') 700 nucleotides of
the Makorin1 mRNA. Moreover, whereas both copies (one from the mother and
one from the father) of the Makorin1 gene can be transcribed, the
Makorin1-p1 pseudogene is paternally 'imprinted', so that only the paternal
copy is expressed.
Normally, Makorin1 mRNA is expressed throughout the animal6. But Hirotsune
et al. found that when the paternal Makorin1-p1 pseudogene was disrupted,
the expression of Makorin1 was markedly reduced in embryos and throughout
birth and weaning. This implies that the pseudogene is normally required for
the high-level expression of Makorin1. Interestingly, of the two forms of
Makorin1 mRNA, only the smaller 1.7-kilobase transcript was downregulated —
the larger 2.9-kilobase copy was unaffected. The long and short forms are
identical except in a region at the so-called 3' end that is not translated
into protein. So, it seems that this region in the long form functions
independently to keep expression levels high.
The authors also wondered whether the imprinting of Makorin1-p1 is
mechanistically central to Makorin1 expression. However, its disruption had
equal effects on both maternal and paternal Makorin1 genes. So it seems that
the imprinting of Makorin1-p1 is an odd happenstance that has little or
nothing to do with its function. Rather, it seems likely that, when
Makorin1-p1 arose, it fortuitously integrated into a chromosomal region that
was already imprinted.
This study5 generates many new and exciting questions. For instance, is
Makorin1-p1 the only Makorin pseudogene that regulates Makorin1? Considering
that disruption of Makorin1-p1 causes only a partial loss of expression of
the functional gene, one might speculate that there are indeed other
pseudogenes whose functions partly overlap, and that the deployment of an
entire pseudogene battalion might be a feasible strategy of gene regulation.
Furthermore, how does Makorin1-p1 regulate Makorin1? The authors found that
the 700-nucleotide 5' region of Makorin1-p1 not only was required but was
also sufficient for regulation in experiments in vitro. These experiments
also suggested that the pseudogene acts sequence-specifically, affecting
only those genes that show some sequence similarity to itself.
Non-protein-coding RNAs have recently been shown to perform a variety of
tasks, such as gene silencing, catalysis and the regulation of development7.
So Makorin1-p1's mechanism of action might involve its non-coding RNA
product, rather than the pseudogene itself. Hirotsune et al. propose that
this product works to stabilize the Makorin1 mRNA (Fig. 1a). They favour a
model in which the first 700 nucleotides of the Makorin1 mRNA contain a
recognition site for a destabilization factor. Because this 700-nucleotide
domain is shared by the Makorin1-p1 mRNA, the expression of the pseudogene
would provide a means of titrating out the destabilizing factor through
direct competition. In this model, the longer Makorin1 mRNA is unaffected
because its 3' untranslated region protects it from degradation. An
extension of this idea is that Makorin1 self-regulates: it has been
suggested that it encodes an RNA-binding protein6, which might be the
destabilizing factor that downregulates the short form of its own mRNA.
Figure 1 Gene regulation by a pseudogene. Full legend
High resolution image and legend (43k)
Given the available data, however, another mechanism could be at work (Fig.
1b). This is suggested by the fact that mRNA stability is usually controlled
by elements in the 3' untranslated region8 — rather than at the 5' end,
where the key 700-nucleotide region of Makorin1 is found. The alternative
mechanism would involve the pseudogene DNA locus directly. For example,
perhaps the 700-nucleotide region in the gene and pseudogene contains
elements that, on binding certain proteins, repress transcription. In this
model the repressor proteins would be limited in availability, so that
Makorin1-p1 would compete for repressor binding. These two models —
RNA-mediated versus DNA-mediated — have mechanistic differences and could be
tested.
Whatever the underlying mechanism, the work of Hirotsune et al.5 is
provocative for revealing the first biological function of any pseudogene.
It challenges the popular belief that pseudogenes are simply molecular
fossils — the evidence of Mother Nature's experiments gone awry. Indeed, it
suggests that evolutionary forces can work in both directions. The forward
direction is driven by pressures to create new genes from existing ones, an
imperfect process that often generates defective copies of the original. But
these defective copies need not be evolutionary dead ends, because pressures
in the reverse direction could modify them for specific tasks. In the case
of Makorin1 and Makorin1-p1, the result of bidirectional selection is that
one gene cannot exist without the other — an example of functional
complicity between a perfected product of evolution and its derivative
castaway. Might the pseudogene copies of other functional genes be similarly
useful?
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Art
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posted 09. May 2003 23:09
From then ARN boards:
I think the implications of this work are not particularly friendly to design. First, it has virtually no bearing on the "junk DNA problem", as this finding is relevant to a vanishingly small proportion of that which is usually called "junk DNA". It's really a non-issue.
Secondly, this report actually provides a means by which some duplicated genes might be preserved, even if non-functional in a protein-coding sense. It actually helps to remove from the "gee whiz, we just cannot explain" file the matter of why some duplicated genes retain function, why some drift into nonfunctionality, why some disappear completely, etc.
Moreover, this report adds to a picture of genomes whereby anything goes - there is no one inviolate rule for the behavior of genes, genomes, "junk DNA", and the like. Anything that chemistry would deem as possible very likely does happen - in contrast to the "precise engineering" POV that is part and parcel of ID theory. It's anarchy in there (the cell, that is). Which makes doing the science ever so enjoyable, if constantly vexing.
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Cre8ionist
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posted 10. May 2003 12:22
quote:
First, it has virtually no bearing on the "junk DNA problem", as this finding is relevant to a vanishingly small proportion of that which is usually called "junk DNA". It's really a non-issue.
It will be used by IDer's I think as another strong counter-argument to the anti-ID pseudogene argument. It also points out that Darwinists don't research areas which they've deemed "failed experiments" due to a false preconception. So-called "junk DNA" will in the long run, I suspect, answer many of the unanswered questions concerning life's program. The cyclops eye (focused on protein coding) of the gradualist will ultimately prove to be a wrong-headed approach, as the Japanese researchers have begun to demonstrate. And if their research is as fruitful as I think it will be, the pseudogene, will become a huge source of embarrassment for the anti-IDer, despite all attempts at minimization..........................................Cre8
[ 10. May 2003, 12:24: Message edited by: Cre8ionist ]
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charlie d.
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Member # 159
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posted 10. May 2003 13:07
LOL Cre8!
That's quite a prediction! There is a chance for ID supporters to really make a difference: set up a foundation to study the potential functions of pseudogenes. Intead of wasting money on AiG, "Dr.Dino", and other creationist organizations, hit darwinians where it hurts: fund real research by real scientists. I wonder why the ICR wastes so much effort on its museum and other "outreach" programs, when it could so easily destroy darwinism piece by piece by analyzing pseudogenes one by one and showing their functionality (maybe they don't believe they are all functional, either?).
On another note, say, if one found one pseudogene that does not have a function, by knock-out experiments and such, would that be an equally big "embarassment" to ID supporters? Would the theory crumble?
[ 10. May 2003, 13:24: Message edited by: charlie d. ]
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Cre8ionist
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posted 10. May 2003 13:48
Well Charlie I'm glad it gives you a laugh. I'm sure the laughter about the importance of so-called "junk DNA" is nothing more than a cover for pain however. It is not IDers, nor Creationists who made sweeping generalizations about the function, or lackthereof, with respect to pseudogenes, it was Darwinists:
quote:
Evolution, in contrast, can easily explain them as nothing more than
failed experiments in a random process of gene duplication that persist in the
genome as evolutionary remnants.
This Miller statement was obviously wrong, the research now shows that. Whether or not all pseudogenes are useful isn't really the point here. Nobody I know of has ever contended that genes won't devolve. But this simple fact now emerges, psuedogenes may have function. They'll need to be tested. Or perhaps you'd like to just continue to skip over them based upon your preconception?
As far as the prediction Charlie, it's not really just mine, remember what the article said:
"In continuing studies, the researchers hope to show the pseudogene-gene
interaction is a general mechanism taking place in many cellular interactions."
Perhaps you think that the words "general mechanism" mean "far fetched", or "hardly used," I don't! With respect to the implied insult to AIG or ICR, I am not now, nor have I ever been a member of either. I do like what they've done for the debate however.
But your anger WRT these orgs. is obvious. Remember Charlie, anger can be the wind which blows out the lamp of intelligence.........................................................Cre8
[ 10. May 2003, 13:50: Message edited by: Cre8ionist ]
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charlie d.
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posted 10. May 2003 15:19
Cre8:
actually, I think the article is pretty good: evolution is a tinkerer, remember, and it doesn't really surprise anybody that it makes the best of what's lying around in the basement. That the paper was published in Nature clearly proves that even the "mainstream" scientific community seems to agree that the findings are interesting and worth disseminating (despite the darwinian censorship that is supposed to prevent people from even working on the subject - aw, shucks!).
Also, not surprisingly, while creationist "scientists" investigate problems like the amount of animal waste produced on the Ark, and ID theorists philophize about mouse traps, without publishing a single research paper in about a decade, it was "mainstream" scientists who researched and published the finding you now hail - aw, shucks!
The point of non-genic DNA is, in fact, exactly the opposite as the strawman argument you propose. Evolutionary theory would not predict that every piece of non-genic DNA would be "junk", but just that much of certain genomes, like ours, would be, based on known molecular processes (duplication and mutation, retrotransposition, "selfish" DNA element replication, etc). That prediction is simply, so far, born out by the facts. If ID advocates and creationists think otherwise, they would do well to put their efforts in pseudogene research rather than "limestone cowboys" and school board-lobbying.
quote:
It is not IDers, nor Creationists who made sweeping generalizations about the function, or lackthereof, with respect to pseudogenes...
Alas, I challenge you to find any sweeping generalization in the professional literature or the writings of any prominent evolutionary or molecular biologist stating that pseudogenes as a whole must be non-functional (that would be a sweeping generalization) - that's certainly not what Miller is saying in the sentence you quote.
[ 10. May 2003, 16:49: Message edited by: charlie d. ]
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Art
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posted 10. May 2003 16:57
quote:
quote:
First, it has virtually no bearing on the "junk DNA problem", as this finding is relevant to a vanishingly small proportion of that which is usually called "junk DNA". It's really a non-issue.
It will be used by IDer's I think as another strong counter-argument to the anti-ID pseudogene argument. It also points out that Darwinists don't research areas which they've deemed "failed experiments" due to a false preconception.
Um, I think the paper in question was authored by people who most likely are "Darwinists". Certainly not IDists.
quote:
So-called "junk DNA" will in the long run, I suspect, answer many of the unanswered questions concerning life's program. The cyclops eye (focused on protein coding) of the gradualist will ultimately prove to be a wrong-headed approach, as the Japanese researchers have begun to demonstrate. And if their research is as fruitful as I think it will be, the pseudogene, will become a huge source of embarrassment for the anti-IDer, despite all attempts at minimization
Once again - the matter of "junk DNA" extends far beyond the miniscule fraction of a typical eukaryotic genome that includes expressed (or unexpressed) pseudogenes, miRNA-coding sequences, and the like. The research under discussion doesn't pertain to the vast, vast majority of DNA that is just there, doing nothing.
A useful exercise for those who believe that "junk DNA" will in fact find a tangible, specific function (like the single pseudogene of which all manner of extrapolation is being made) is to consider the fact that "junk DNA" content varies wildly - by many orders of magnitude - in eukaryotes. This in and of itself tells us that no life-vital functions involve these sequences. Thus, IMO, the only way to rescue functionality is to propose some sort of highly species-specific function. But there is, as far as I know, no data that lends credence to this idea. Until something comes to light, the obvious conclusion as to the functionality (or lack thereof) of sequences that cannot encode RNA, are not transcribed as RNA, and are quite completely dispensible when it comes to essentiality, is that they have no function.
(One final aside for now - the "cyclops eye" that cre8 mentions was long ago replaced with a POV that is, IMO, less acceptable to ID theorists than a purely protein-centric view. I speak, of course, of the window on life that is afforded by the RNA World hypothesis. It's a bit ironic that a phenomenon that is so heavily influenced by an RNA-centric view of things is being championed as in some way contrary to "Darwinism". For it is certainly nothing of the sort.)
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Pim van Meurs
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posted 10. May 2003 17:10
Creationist:
This argument can now go the way of the vestigial organ, biogenetic law, peppered moth, chimp/human %98 DNA similarity, reptile to bird transition, lightspeed can't decrease arguments.
I think that some careful analysis of the arguments about for instance the peppered moth and the 98% DNA similarity will reveal that they are hardly Icons Of Evolution that have been rejected. As far as the paper on pseudogenes, the researchers claim to have shown that some pseudogenes may have function which does not mean that all pseudogenes have function. It seems to early to suggest that pseudogenes all have function. Similarly it seems to early to dismiss the work by many researchers on the peppere moths for instance, the significant evidence showing the phylogeny of humans and chimpanzees and other primates etc. etc. I realize that this may not be the proper forum to discuss these issues of Icons and their present status but I would like to state at least my position that in spite of creationist's claims, many of these icons still remain standing quite strongly. If creationist is interested in exploring what he believes are relevant issues to ID then by all means I would encourage such an effort
As far as your Miller quote
quote:
The theory of intelligent design cannot explain the presence of nonfuntional pseudogenes unless it is willing to allow that the designer made serious errors, wasting millions of bases of DNA on a blue print full of junk and scribbles.
Do you suggest that ID can explain the presence of non-functional pseudogenes?
[ 10. May 2003, 17:15: Message edited by: Pim van Meurs ]
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Cre8ionist
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posted 10. May 2003 18:24
Rather than spend the next several weeks covering old material on pseudogenes Charlie, I'd rather make one last post and give you the final word. My position is clear, whether it's accepted by anyone else or not isn't at issue, clearly the Japanese researchers have a different view of pseudogenes than has been expressed by many evolutionists, whether they believe in God as Creator or not I can't say.
First, here are a couple of articles from Creationists for those who are interested, with a different take on pseudogenes.
http://www.trueorigin.org/pseudogenes01.asp
This new research bolsters the Creationist position, and weakens the Darwinists position. IMO
The Darwinist position has been incorrect, here is evidence of that (italics mine):
Introduction to Evolutionary Biology
quote:
There are other sites in the genome where nucleotide differences do not effect protein sequences. The genome of eukaryotes is loaded with 'dead genes' called pseudogenes. Pseudogenes are copies of working genes that have been inactivated by mutation. Most pseudogenes do not produce full proteins. They may be transcribed, but not translated.
Or, they may be translated, but only a truncated protein is produced. Pseudogenes evolve much faster than their working counterparts. Mutations in them do not get incorporated into proteins, so they have no effect on the fitness of an organism.
http://www.talkorigins.org/faqs/faq-intro-to-biology.html
Keith Robison
quote:
One argument against an intelligent designer is the amazing amount of flotsam and jetsam in genomes. The human genome is 90-95% apparent junk, useless sequences, many of which resemble functional genes, but are clearly beaten up beyond working order (pseudogenes).
http://www.talkorigins.org/faqs/behe/review.html
Evolution FAQ Is Evolution Science? Junk DNA
quote:
What's more, with much of this junk DNA we can make pretty good
guesses as to how it came to be. A lot of it (such as
pseudogenes) appears to be copies of other pieces of DNA that
have mutated such that they are no longer functional. There are a
variety of mutations that can result in non-functional genetic
code, so junk DNA essentially represents errors in our DNA.
http://atheism.about.com/library/FAQs/evolution/blfaq_evolution_evidence12.htm
And finally, one from the Federation of European Biochemical Societies which shows how widespread the mistaken view is:
quote:
Vanin [1] stressed that the term pseudogene is only applicable to sequences that
are related to another sequence but are defective.
http://www.web-editions.com/febs_article.htm
I'll not attempt to expose the plasticity of your theory, you'll accomplish that on your own. Just remember, from now on think twice before using the pseudogene argument.
Briefly Pim, yes I think ID/Creationism can explain non-functional genes, loss of information is certainly allowed for in ID. As for whether the points I raised are actual icons, that have been rejected, I can only say, they are much less effectual as an argument now. And they are used with less frequency from what I can tell, at least in the forums/chats I visit.
Art,
quote:
Once again - the matter of "junk DNA" extends far beyond the miniscule fraction of a
typical eukaryotic genome that includes expressed (or unexpressed) pseudogenes.
Well according to one estimate I just read during research there are up to 15,000 pseudogenes (humans), considering the total number of genes I'm less inclined to downplay their significance.
Nothing else really to say right now (that could potentially change), you're certainly entitled to your view, thankfully, I'm entitled to disagree...................Cre8
[ 11. May 2003, 13:51: Message edited by: Moderator ]
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Pim van Meurs
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posted 10. May 2003 18:57
Creationist: As for whether the points I raised are actual icons, that have been rejected, I can only say, they are much less effectual as an argument now.
Are they? I would say that many of them have become stronger arguments. As I said, I would love to discuss these icons and their relevance to ID in more depth if there is such interest.
As far as pseudogenes are concernedd, the observation that some pseudogenes may not be pseudogenes hardly undermines the argument.
As far as pseudogenes and ID, I am not sure how you would like to link the two but I am curious nevertheless.
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charlie d.
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posted 10. May 2003 21:02
Cre8:
thanks for providing the "sweeping generalizations" we were talking about. Of course, none of your quotes from evolutionists sources claims that all pseudogene-like sequences are necessarily non functional, and are thus not "sweeping" at all.
On the other hand, the following does make a sweeping (i.e., all-covering) statement: quote:
As the function of more pseudogenes is being uncovered by testable and repeatable science, it is evident that these genetic elements, which are copiously spread in the genomes of different organisms, have been created with purpose.
and it comes from your creationist links (btw, maybe you have not read both of them, but they are exactly identical, although from different sources. Generally speaking, one does not usually make a stronger point just by repeating the same thing twice). I also note how the statement that "the function of more pseudogenes is being uncovered by testable and repeatable science" directly contradicts your original claims about "cyclop's eyes" and lack or research on pseudogenes by darwinian scientists. But hey, who needs consistency anyway.
Going back to the point, based on that quote you provided, would you agree that
a) the finding of even a single pseudogene with NO function (say, no expression detected, no phenotype changes in knock-outs) would prove that at least for that segment, no "purpose" exists?
b) if that were the case, that the pseudogenic segment in question was there most likely by chance, and not by design?
And
c)if so, and such segment happened to be shared between species A and B, but not found in other related species, that this would be strong evidence for common descent of species A and B?
Looking forward to your answer.
PS: I just noticed this: what exactly do you think "Embargoed by nature" means, relative to this article? It sounds deeply meaningful, I know.
[ 10. May 2003, 21:51: Message edited by: charlie d. ]
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Cre8ionist
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posted 10. May 2003 23:16
Sorry Charlie,
The second link was supposed to be the Woodmorappe article.
Here it is:
http://www.answersingenesis.org/Home/Area/Magazines/tj/docs/tj14_3-jw_pseudo.pdf
Acrobat reader needed.
Don't normally respond again but since I messed up on the link, I will briefly.
I agree with A & B (if A could be proven, difficult as it may be), couldn't agree with C til I saw the details. Hopefully you wouldn't be alluding to the probability of two of the same pseudogenes in different lines of descent eliminating the possiblility of design, that would put you in quite a predicament.........................................Cre8
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