Is There “Junk” in Your Genome? Part 3
Today's entry was written by Dennis Venema. You can read more about what BioLogos believes here.
One of the challenges for discussing evolution within evangelical Christian circles is that there is widespread confusion about how evolution actually works. In this (intermittent) series, I discuss aspects of evolution that are commonly misunderstood in the Christian community. In this third of several posts on “junk DNA”, we explore how a specific form of pseudogenes called “processed pseudogenes” arise within genomes.
“Pseudogenes” (literally “false genes”) are generally viewed as sequences in genomes that, though they have high sequence similarity to “real” genes, do not have a function. Historically they were found before the advent of whole-genome sequencing as alternate forms of genes that lacked certain features. Some pseudogenes have characteristics that indicate they are derived from “real” genes – a class of pseudogenes called processed pseudogenes. In this post we’ll discuss the mechanism by which processed pseudogenes arise, and then discuss how a small fraction of them pick up functions and become “real” themselves.
Some assembly required
Processed pseudogenes arise from gene sequences that are transcribed into RNA, and spliced together to form “messenger RNA”, or mRNA, which is what the cell uses to guide protein translation. While I discussed how genes work in the last post in this series, let’s briefly revisit the topic with a view to certain details that we’ll need to understand how processed pseudogenes come to be.
Genes are segments of DNA on chromosomes housed in the nucleus of the cell. In order to make a specific protein encoded by the gene, a “working copy” of the sequence is transcribed into RNA, which for our purposes you can think of as a single-stranded version of DNA (DNA being double-stranded, of course). This RNA copy is then processed to remove sequences that interrupt the protein sequence code. These sequences are called introns, and they are spliced out of the RNA to produce what is called “messenger RNA” or “mRNA” – since it is now ready to carry the protein sequence code, or “message” out to the place where the protein will actually be constructed (outside the nucleus, in the cytoplasm).
While mRNA is a single-stranded molecule, an enzyme called reverse transcriptase is capable of re-creating a double-stranded DNA copy of it. This enzyme function is not a normal cellular function, since the point of producing mRNA in the first place is to make protein, not DNA. Cells don’t need to make DNA copies of RNA transcripts.
So, why is there reverse transcriptase present in cells at all? The answer, as it turns out, is that this enzyme is part of a type of transposon found in many organisms. We discussed transposons in a previous post in this series. In brief, transposons are self-replicating DNA segments that copy themselves and spread within genomes – a sort of minimalist DNA parasite. One class of transposons called retrotransposons copy themselves into RNA and then back into DNA using reverse transcriptase – so this enzyme is present in cells as a result. On occasion, reverse transcriptase makes a DNA copy of a host cell mRNA instead of its intended target (the transposon RNA):
This DNA copy of the mRNA may, at a low frequency, re-enter the nucleus and insert itself into a chromosome. The result is a sequence that is highly similar to the original gene, but lacking several key components: introns are missing, obviously, but also the original “parent gene” chromosomal DNA regulatory sequences. Processed pseudogenes, when inserted, have no function the cell requires – indeed, the cell was getting along just fine without it before it inserted. Accordingly, the vast majority of processed pseudogenes in genomes are not under natural selection, but may mutate freely without consequence.
Seeking the living among the dead
For a tiny fraction of processed pseudogenes, however, this may not be the end of the story. As we saw previously for transposon insertions, in rare cases the arrival of new DNA sequence at a chromosomal location might alter a cellular function and then be selected for on that basis. So to in this example, with an added twist: the fact that the processed pseudogene and its “parent gene” share a great deal of sequence in common raises the possibility that they could interact as RNA copies. If the processed pseudogene lands in a chromosome location that has regulatory sequences nearby, it might be transcribed into RNA as a result. If this happens, the interactions between the two RNA molecules may alter the regulation of the parent gene. If this new interaction has a selectable benefit, the processed pseudogene in effect has become a new gene in its own right and future mutation and selection may hone this nascent function over time.
As we mentioned previously, the fact that transposons can be converted into functional sequences does not “confer” functionality on all transposons. Nor does the (very interesting) finding that “the dead may rise” from pseudogene to gene indicate that all processed pseudogenes are likewise functional or about to become so. Rather, both examples illustrate that new biological information can be obtained through the natural processes of mutation (in this case, duplication and insertion of DNA sequence to a new location in the genome) and subsequent selection.
In the next installment of this series, we’ll examine one final form of non-functional DNA present in genomes, and one that is of great discomfort to antievolutionary views: unitary pseudogenes.
For further reading:
Esnault, C., Maestre, J., and Heidmann, T. (2000). Human LINE retrotransposons generate processed pseudogenes. Nature Genetics (24); 363 – 367.
Zheng, D., and Gerstein, M.B. (2007). The ambiguous boundary between genes and pseudogenes: the dead rise up, or do they? Trends in Genetics (23); 219 – 224.
Dennis Venema is Fellow of Biology for The BioLogos Foundation and associate professor of biology at Trinity Western University in Langley, British Columbia. His research is focused on the genetics of pattern formation and signalling.
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February 3rd 2012
Dennis, a quick couple of questions.
February 3rd 2012
Hi Crude,
February 3rd 2012
Actually, I’d like you to tell me how you see evolution as guided, if at all, regardless of my reply.
February 3rd 2012
I’m not trying to be coy here, but much turns on precise definitions.
February 3rd 2012
No problem at all.
February 3rd 2012
Why should foreknowledge (omniscience) necessarily imply guidance (omnipotence)? —they are, after all, two distinct words and concepts. I can re-watch a movie with complete foreknowledge of everything that will happen and yet without having had any influence whatsoever in making it happen as it did. (foreknowledge without guidance). I’m not suggesting that those concepts aren’t both melded in God—I do think he’s both. But one should also distinguish between omnipotence and strong predestiny—i.e. not only *can* God do everything, He *does* do everything. And there is a significant difference there too which I, in turn, would dodge answering until terms were better defined or the necessary caveats in place. All the same, Dennis, I think Crude may be letting you off the hook too soon. Why not guided or unguided even with omniscience in place? Isn’t the old question of how God threw or set the dice still a live one on the table for us all?
Reply to this comment—Merv
February 3rd 2012
Merv,
February 3rd 2012
Crude,
February 3rd 2012
I think God is omnipotent and omniscient. That should pretty much answer all questions on that front.
February 3rd 2012
“I think God is omnipotent and omniscient. That should pretty much answer all questions on that front.”
I agree. God guides evolution in the same manner and to the same extent He guides the weather.
That answers your question as well.
February 3rd 2012
It’s a shame, then, that I didn’t ask you the question, nor am I really interested in your answer. But if you wanted a completely disinterested “that’s nice” from me, by all means, it’s yours.
February 4th 2012
Your courtesy and intellectual integrity is noted.
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February 3rd 2012
Merv,
“I can re-watch a movie with complete foreknowledge of everything that will happen and yet without having had any influence whatsoever in making it happen as it did.”
I was thinking the exact same thing when I read your words! (Now, don’t tell me you were thinking “Saving Private Ryan”. That would be too weird!)
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February 3rd 2012
Dennis Venema,
“if God is omnipotent and omniscient, is there anything at all in the entire cosmos that is, in your view, “unguided”?
As I understand it, traditional Christian teaching says that God does not put, or in any way guide, anyone into hell; yet He always knew that’s where certain people will end up.
Based on this, the answer to your question would be Yes.
Secondly, IF you think everything is God-guided, even so-called stochastic processes, would you recommend striking “stochastic” and “random” from the dictionary, or at least from your vocabulary?
Reply to this commentFebruary 4th 2012
Crude
Reply to this commentA good question too often ducked in TE circles. It seems to me than on this question hinges whether theistic evolution is a coherent philosophical and theological position, or just materialist science with a comforting personal pietism nailed on.
It worries me that on another recent thread of nearly 150 posts, hardly anyone was willing to commit to an answer.
February 4th 2012
Jon,
February 4th 2012
Dear Crude,
February 4th 2012
I’d say that God’s interaction with us is continuous. Like the city, God never sleeps.
Reply to this commentFebruary 4th 2012
“If I take the wings of the morning and settle at the farthest limits of the sea, even there you hand shall lead me, and your right hand shall hold me fast. If I say, ‘Surely the darkness shall cover me, and the light around become night,’ even the darkness is not dark to you; the night is as bright as the day, for darkness is as light to you.”
Reply to this commentFebruary 4th 2012
Darrel
I can’t answer for Crude, any more than you can for Dennis. But I don’t think “supernatural” was what he was asking about. He clarified:
That seems to me to cover more than “God initiated natural laws and is the ground of existence”, but also possibilities such as cosmological fine tuning, genetic front-loading, the overseeing of contingency (which is NOT law-driven or it would come under Monod’s “necessity”); all these quite apart from any question of “supernatural intervention”. The essence is “By whatever means, does God determine the specific outcomes of evolution?” Or, as he continues in the same post, “Was he surprised at any stage?”
Reply to this commentThe answer to that determines whether one can meaningfully talk about “junk DNA” etc, and also defines a difference from naturalistic evolutionists, many of whom are happy for people to believe in God as long as his existence makes no actual difference to anything and evolution can still be said to be “undirected”.
Your quote from Ps 139, of course, raises the same kind of questions, and would suggest that, in the human sphere at least, you yourself maintain God’s actual control, for the psalmist goes on to say, “All the days ordained for me were written in your book before one of them came to be.”
February 4th 2012
Theologians within orthodox Christianity differ greatly on the meaning of the phrase “all the days ordained for me were written…” There is one thing however, on which we can all agree—-God’s Presence is always with us and we are never removed from his love.
Reply to this commentFebruary 4th 2012
One of the great pleasures of creativity , in my experience, is being surprised at the outcome. One steps back and says “Did I make that? I only had a vague idea of what I wanted when I started, but now I am amazed with the outcome.” One can never experience that with out realizing an idea.
February 4th 2012
Yeah, Hornspiel - but you and I are creatures. We don’t live in eternity, and we don’t make Universes. And much of our creative surprise - maybe better to say joy - is because it’s a gift of God’s grace when our small efforts actually turn out good.
Reply to this commentSo it’s actually, to be as charitable as possible, fudging the issue vaguely to equate “surprise” with “love”, without being willing as well to affirm that, non-figuratively, “God foresees” or else “God does not foresee.” Or to be unwilling to say whether or not “God assigns every created being its useful function in his cosmic temple” (which is at least a major part of the universal message of Genesis 1). Both these attributes of God are at the heart of every major strand of historic Christianity, not to mention the other Abrahamic faiths.
Therefore Crude was being not in the least out of line to ask, on a site dedicated to reconciling science to Christian faith, how these doctrines are handled. So far, unfortunately, the answer seems to be “cagily”.
February 4th 2012
Darrel,
February 4th 2012
Sorry that I’m not Dennis or Darrel, but while you’re waiting for their reply, let me at least give the obvious answer (which you seem to have given yourself already, and which seems to me to be a necessary conclusion from what Darrel has already written).
Reply to this commentYou ask: “what knowledge of and power over evolution did God have?”
Answer: everything—both knowledge and power. God did it all. God knew it all. (I still maintain ‘free will’, though. Yeah I know—it’s a mess.)
You ask: “Was He
surprised by the results of evolution?”
Answer: No.
The reason I give (my) answers here is because I want to hear your followup (the ‘so what ...’) that comes from this. I think I got some of it from what you wrote earlier: Do you maintain that given my answers I should strike the word ‘random’ from my vocabulary? If so, I would have to ask you: why? ...since that word has nothing to do with God’s perspective and everything to do with yours and mine.
—Merv
February 4th 2012
Merv,
February 4th 2012
Dear Crude,
February 4th 2012
Darrel,
And I’ll even ask a followup question. You said that my belief is entirely compatible with science and Biologos’ mission. Of course, some (I have some atheists in mind here particularly) would say my views, as stated, are not compatible with science. That the idea that God knows, has power over, and intended the results of evolution - even without ‘tinkering’ miracles - is incompatible with science.
February 4th 2012
Dear Crude,
February 4th 2012
So Darrel, you admit don’t know everything there is to know about God and His ways? That sounds like humility to me. Quite unlike the fundies.
Reply to this commentFebruary 5th 2012
“Fundie” (n): contraction of “fundamentalist”.
The full meaning of the term, therefore, can be given by something like ‘stupid sumbitch whose theological opinions are considerably to the right of mine’. (Alvin Plantinga)
As he explains:
its cognitive content can expand and contract on
demand; its content seems to depend on who is using it. In the mouths of certain
liberal theologians, for example, it tends to denote any who accept traditional
Christianity, including Augustine, Aquinas, Luther, Calvin, and Barth; in the
mouths of devout secularists like Richard Dawkins or Daniel Dennett, it tends to
denote anyone who believes there is such a person as God. The explanation is
that the term has a certain indexical
element: its cognitive content is given by the phrase ‘considerably to the
Reply to this commentright, theologically speaking, of me and my enlightened friends.’
February 4th 2012
February 4th 2012
Does God work harder on mutations after people are exposed to radiation?
Reply to this commentFebruary 4th 2012
The evidence shows that radiation damage induces cellular mechanisms of DNA-repair and specific mutagenesis (Weigle mutagenesis), so the cells themselves are working harder.
Reply to this commentSo the question becomes whether God oversees cellular mechanisms. Jesus does say the very hairs on our head are numbered (and they tend to fall out after irradiation). I’d hate to think he only numbers them when we’re at the hairdressers.
The bigger question, to cite Darrel’s psalm, is whether “all the days ordained for me except the one where I got a belt of radiation were written in your book before one of them came to be.” If not, it’s not a very comforting passage after all.
February 4th 2012
The bigger question? Why not just the question?
Reply to this commentFebruary 4th 2012
Why not just the answer?
Reply to this commentFebruary 4th 2012
Sure, the answer to my question in 67596
Reply to this commentFebruary 4th 2012
Understanding this pseudogene thing isn’t rocket science…its more like a Rube Goldberg machine. Quite a ride. Thanks for posting this Dennis
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February 4th 2012
Darrel Falk,
“Has God worked in super-natural ways in the history of life, or has God chosen to work only through his customary activity—that which can be studied through science? The answer to that question remains a mystery… Was God’s “non-regular” way of working necessary to drive life in the direction God wanted it to go? We don’t know. Neither Scripture nor science, provide a clear basis for answering those questions, so how would we know?”
So, bottom-line, as far as the degree of God’s involvement in origins, it’s not a matter of science or Scripture.
It all comes down to faith. Correct?
If correct, would you say that, to a significant and perhaps complete extent, we’re just wasting our time at this website?
Reply to this commentFebruary 4th 2012
Dear “Don’t blame me…”
posting new comments.
February 4th 2012
Darrel Falk,
I don’t think I missed your point at all.
You said that neither science nor Scripture provides a clear basis for knowing whether God used “natural” or “supernatural” means in “the history of life” (i.e. evolution).
So, again, in your view, science can’t answer the question, and Scripture can’t answer the question.
It’s simply a matter of faith.
Reply to this commentFebruary 4th 2012
Faith in what? Both totally involve our Creator and both, as I see it, are equally consistent with Scripture and science. Which of the two should I take on faith and why?
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February 4th 2012
Darrel Falk,
“Faith in what? Both totally involve our Creator and both, as I see it, are equally consistent with Scripture and science. Which of the two should I take on faith and why?”
I’m sorry. I was trying my best to be clear.
First, let me clarify that by “faith”, in this context, I meant a belief that is completely independent of science or Scripture. For example, if Joe tells you his favorite color is blue, you might then have faith that his favorite color is indeed blue. Or you might have faith that you actually DID have such and such a dream last night.
Now, let me try restating what I think you have said:
(a)
If one believes God “supernaturally” intervened throughout the course of evolution (i.e. trillions of biological miracles), then that’s simply a choice of faith, not a matter of science or Scripture. Or
(b)
If one believes God did NOT “supernaturally” intervene throughout the course of evolution but instead just got it started then kept hands-off thus allowing only “natural” processes to run their course, then that’s simply a choice of faith, not a matter of science or Scripture.
BECAUSE, as you said, “Neither Scripture nor science, provide a clear basis for answering those questions.”
I hope that’s clear.
Reply to this commentFebruary 5th 2012
Dear Don’t…
posting new comments.
February 5th 2012
The above article notes beneficial, or at worst inconsequential, effects of genetic mutations:
“Accordingly, the vast majority of processed pseudogenes in genomes are not under natural selection, but may mutate freely without consequence.”
“If this new interaction has a selectable benefit, the processed pseudogene in effect has become a new gene in its own right and future mutation and selection may hone this nascent function over time.”
“new biological information can be obtained through the natural processes of mutation (in this case, duplication and insertion of DNA sequence to a new location in the genome) and subsequent selection.”
I just saw a book on Amazon relating to this. It’s by a Cornell professor who is saying that genetic mutations are usually harmful and never lead to an increase in genetic information. He also says the human genome, because of ever-accumulating mutations, is slowly but inexorably degrading!
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February 5th 2012
Here’s the link:
http://www.amazon.com/Genetic-Entropy-Mystery-Genome-Sanford/dp/0981631606
Reply to this commentFebruary 5th 2012
Amazon sells books by many other young earth creationist authors. None of them are scientific.
Reply to this commentFebruary 5th 2012
Dennis,
Reply to this commentAs always I appreciate your work. Mobile genetic elements which transfer pseudogenes appear to a rapid way to change genomes. As a YEC I am interested in this as you know. How do the mechanisms you explain here:
1 influence the dating of human genome change and the diversity we see in the human genome?....i.e., could insertion of pseudogenes increase genome diversity and correspondingly decrease the number of founding couples needed for human evolution.
2 support the idea of irreducible complexity in the HGT found in microbes….for instance a Nature article a few years ago showed that HGT transfer was most likely the way that microbes received new genetic information because point mutations could not supply all the genes necessary for operon function, i.e. all the genes were required to be transfered because most functions of microbes were controlled by operons…in a sense this article verified that many microbial systems were IC.
perhaps my examples do not apply…am I comparing apples and oranges here?
Thanks again,
Joe
posting new comments.
February 5th 2012
Darrel Falk,
I started reading your comment #67661 and thought you were joking.
But I guess you weren’t.
I was unclear, justifiably I think, on what your position was. For your comment #67661 seemed to conflict with # 67588.
In #67661 you’re saying that neither science nor Scripture can confirm whether God “supernaturally” intervened in evolution. This is different from at least part of #67588 where you seemed to indicate that neither science nor Scripture can confirm anything at all about God’s “involvement” in evolution: “Has God worked in super-natural ways in the history of life, or has God chosen to work only through his customary activity—that which can be studied through science? The answer to that question remains a mystery.”
I guess #67661 is your true position?
In either case, I think you WOULD say that Scripture is silent on the specifics of the degree of God’s involvement?
Finally, I assume you were talking about evolution when you said “we know that much of creation was carried out through God’s customary (natural) way of working.” But who is “we” and what do “we” “know”?
The “we” certainly isn’t everyone in the U.S. nor everyone in the Gallup poll (see bottom page 2 of “Behold the Man” blog).
And certainly we don’t objectively “know” evolution is true, in a “scientific proof” sense. Otherwise, no controversy would still exist over the validity of evolution theory. And we probably wouldn’t be blogging here.
Actually, please skip the “know” part of the question. But who is “we”?
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February 5th 2012
Darrel,
I was wondering about BioLogos’ mission statement: “The BioLogos Foundation explores, promotes and celebrates the integration of science and Christian faith.”
Science and Christian faith?
As far as Science, does BioLogos have blogs about NASA projects, cancer treatments, stem cell research, or any number of other scientific/medical pursuits?
Any besides particular research involving the word evolution?
As far as Christian faith, do you consider evangelicals or Catholics to be un-Christian? You said “We need protestant, conservative protestant, theologians and philosophers addressing questions like this… The bottom line is that BioLogos is initiating the conversation for conservative protestants.”
Should the BioLogos mission statement be revised to “The BioLogos Foundation explores, promotes and celebrates the integration of Evolution and conservative Protestantism”?
Reply to this commentFebruary 5th 2012
Hi Crude,
February 6th 2012
Dennis,
February 7th 2012
By the way, Dennis. I’d like to also ask you the same question Darrel Falk answered - I really appreciate his (the ED of this site, I’m flattered!) input, and loved his answer.
February 7th 2012
Hi Crude,
February 7th 2012
Dennis,
February 7th 2012
On the subject of the original post, this article seems very relevant: http://rnajournal.cshlp.org/content/17/5/792.abstract Unfor.tunately only the abstract is available free online.
Reply to this commentIt does show again the risk of the “Junk of the Gaps” argument, and raise the question (once more) of whether it is more valid to look at pseudogenes as rubbish that, fortuitously, finds an extensive range of functions; or rather as a functional element that either fortuitously loses function - or perhaps, whose function is at a more sophisticated level than that of mere coding genes.
Incidentally, as Mike Gene points out in his blog, since transposons do no significant harm and may be even occasionally co-opted to function, they cannot correctly be said to be parasitic, where the relationship to the host is definitionally harmful. Symbiosis might be a better term since both “parties” benefit - but if one still wishes to downplay function, “commensal” would be a less-loaded and more correct term.
Mike, incidentally, is not happy with the view that transposons are “alien” elements at all.
February 7th 2012
In my family we used to have a family joke “which one is the doctor?” My grandma would invariably come into a movie or TV show in the middle and ask to be brougth up to date way after it was too late. In one, she asked the above question, and we all decided it was the perfect example of this behavior. So whenever someone got involved in a discussion in the middle, one of us would ask “which one’s the doctor?” I feel like Grandma in this discussion as I just joined Biologos and this is the first thread I have read. Is it OK to butt in? I will offer the briefest comment and then you can throw me out or invite me back. It has to do with “mystery” and I have always pondered whether that meant something we can never know, by its nature, or something that might somehow be solved or at least approached more closely given more effort to find and think about information. I belive that the mystery of free will is something we can know more about, but perhaps never totally decode, just as we might be able to accelerate an object eventually to near light speed but never quite get there - like the “Library”
Reply to this commentFebruary 7th 2012
Hi Vince,
Reply to this commentWelcome aboard!!! Of course it’s okay to butt in, but you also might like to check out the “Questions” and “Resources” links on the menu to get up to speed. Maybe you have already done so. Trouble is, there is a lot of material!
I think you are right that we will never fully understand certain mysteries of the faith, such as free will. This is not to be confused with a scientific mystery (ignorance), which is open to investigation.
February 7th 2012
Crude asks:
If Dennis and others are going to make the case for evolution-as-providence, they’ll have to explain it to mainstream science, who answer Crude’s question with an unqualified no:
Reply to this commentFebruary 7th 2012
Sorry—eEmphasis didn’t come through the editor, but you get the idea—Futuyma was pretty clear even without my italics…
Reply to this commentFebruary 7th 2012
Actually, I think Douglas Futuyma’s statement is a little more complicated. Probably moreso than he himself thought or intended.
February 8th 2012
I guess I introduced Futuyma to act as a sort of foil against the clintonesque answers provided by Biologos to your initial question. Sure, water can be channeled or put under pressure by an intelligent agent to achieve a certain end. But if you use erosion to form a canyon, are you not explicitly guiding it? Of course you are. There is a huge difference between that, and simply turning on the faucet and leaving natural law to its own devices.
To return to your original question, if evolution was God’s means of creating, then it has to have been guided (even if the guidance is done in some subtle way that can’t necessarily be detected). Without guidance and engagement at some level, in some way, “let us make man in our image” becomes “Hmm, look what happened,” which is not at all consistent with any flavor of Christian theology I’m familiar with, all references to mysteries notwithstanding.
Reply to this commentFebruary 8th 2012
Chip,
February 8th 2012
In Biblical terms a “mystery” is something once hidden, now revealed. But we’re using it here as “apparent inconsistency,” eg “how God balances delight in freedom with sovereignty”.
Reply to this commentThe question is partly who sets up such mysteries. For example, the Bible clearly talks about human freedom and accountability, yet equally clearly about God’s sovereign ordering of events including human actions. Reformed thinkers accept that as a mystery, with the resolution presumably somewhere in the interface between God’s dwelling in eternity and infinity and ours in the flesh. In the end, though, if God says directly that he sees them as compatible, and we don’t, then accepting the mystery is a necessary part of humble faith.
The idea of “the freedom of creation” is different. It’s hard to argue from Scripture, and seems to have arisen only recently from speculation about what God’s nature ought to be, by projecting the idea of human liberty on to inanimate things. Logically it runs into problems in that unless one has a vitalistic view of nature, it’s not clear how non-sentient rocks and particles would want, or use, “freedom”.
Yet the “mystery” that this hypothesis sets up for God’s sovereignty is a starkly logical one: if he does not direct nature’s ends by natural law, does not intervene by miracles and does not oversee the outcome of stochastic events the “mystery” is simply that one has arbitrarily removed all conceivable (and historically Christian) means for his activity and tacked on “yet he’s sovereign anyway.”
For accepting mystery to be a virtue one needs to be pretty damned sure that both sides of the mystery are actually true. Otherwise it may just be just muddled thinking.