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Friday, October 31, 2014

Genetic Redundancy – An Amazing Design

Posted by jlwile on May 24, 2010

Rotating Anmation of DNA
(Animation in the public domain)

As I mentioned previously, Dr. Peter Borger has an amazing series of articles on genetics over at Creation Ministries International’s website. He is putting together a very impressive interpretation of the genome based on what has been learned about genetics over the past few years. He starts his series with a discussion of genetic redundancy, which is truly incredible.

The article begins by discussing something that has been known for quite some time: It is possible to disable a gene so that it no longer produces the protein it is supposed to produce. This technique is called gene knockout, because it as if the gene has been “knocked out” of the organism’s genome. The organism is referred to as a knockout organism or just a knockout.

Why would you study a knockout organism? Well, imagine that you have identified a gene but don’t really know what it does for the organism. If you create a version of the organism with that gene knocked out, any negative effects that you see will most likely be the result of the missing gene, so that will give you some idea of what the gene does.

This is a great experimental procedure that has produced a lot of genetic understanding over the years. However, it has also produced a very interesting result: often a knockout organism is not significantly different from the standard (usually called wild-type) organism. In other words, some genes can be knocked out of an organism with little or no effect on the organism itself.

This might sound surprising to someone who is not familiar with the genetics literature, but it really isn’t. In fact, geneticists thought they had an explanation for this interesting result…until experiments over the past decade or so really upset the applecart.

In his article, Dr. Borger discusses several of these experiments, but I want to concentrate on just one of them. It is a ten-year-old study of yeast (Saccharomyces cerevisiae) knockouts, and the results are truly stunning.

Before I discuss the results of the study, let me explain how geneticists thought they could understand the fact that many knockout organisms are not significantly different from their wild-type counterparts. It is well known that genes can duplicate, and that duplication is supposed to be one of the principle means by which evolution occurs. After all, if a gene duplicates, the duplicate can supposedly mutate away unfettered by selection, because the original is still producing the needed protein. This unfettered mutation can eventually cause the duplicated gene to become a completely different gene, thus allowing information to be added to the genome. As I have mentioned previously, however, a recent study casts doubt on this speculative mechanism.

However, even if gene duplication is not a good explanation for how information might get added to a genome, it was thought to be a good explanation for the fact that some genes can be knocked out of an organism without significantly affecting it. After all, if that gene has a duplicate, it doesn’t matter if it is knocked out. The duplicate can take over. As long as the duplicate hasn’t mutated a lot from the original, it will end up producing a protein that can at least mostly do the job that the knocked out gene’s protein is supposed to do.

Well, the study linked above (originally published in Nature Genetics) tested this explanation and found it to be incredibly lacking. Basically, it looked at how well different knockout yeast survived in five different environments. The author makes a good case that the five environments he chose would be able to test a wide range of survivability issues in the yeast. As expected, he found that knocking out some genes produced severely negative results for survivability, knocking out some genes produced partially negative results for survivability, and knocking out some genes had no significant effect on survivability.

Next, he correlated those results with whether or not the gene had a duplicate, and if it had a duplicate, how many duplicates existed. Now, of course, because of mutation, it is assumed that a duplicate will not be an exact match to the original gene. Thus, what the author really did was look for paralog genes – genes that look so similar to the original that they are assumed to be the result of duplication followed by mutation.

Here’s what he found:

When compared with genes whose loss of function results in severe fitness defects, genes whose loss of function results in a weak or no fitness effect are not more similar to their closest paralogues, both in sequence and temporal expression pattern. They are also not part of larger gene families whose members are, on average, more similar in sequence or expression to the gene mutated. Furthermore, they are not related to other yeast genes in about one-half of the cases studied.

If you are having trouble dealing with the jargon, let me boil it down. In roughly half of the knockout genes that had no effect on survivability, there were no paralogs. Thus, there is simply no way the standard explanation based on gene duplication could be right for those genes. In addition, for the other half of the knockout genes that didn’t affect survivability, there was no pattern in terms of how many paralogs existed or how close the paralogs were to the original gene. If gene duplication were the answer to this issue, then one would think that the closer a gene was to its duplicate, the weaker the effect associated with knocking out the gene. In the same way, the more duplicates that exist, the weaker the effect associated with knocking out the gene. His experiment saw none of these expected results. That’s why he concludes:

Thus, although gene duplications may be responsible for a fraction of weak null-mutation phenotypes they contribute little to mutational robustness on a genomic scale.

So what is the proper explanation for the fact that knocking out some genes has little or no effect on survivability? Well, in Dr. Borger’s opinion, it is that the genome is made up of many networks of redundant genes. As he says, many genes

are involved in regulatory networks that detect and process information in order to keep the cell informed about its environment. The proteins operating in these networks come as large gene families with overlapping functions. In a cascade of activation and deactivation of signalling proteins, external messages are transported to the nucleus with information about what is going on outside so it can respond adequately. If one of the interactions disappears, this will not immediately disturb the balance of life. The buffering capacity present in redundant genetic networks also provides the robustness that allows living systems to propagate in time.

Now what does that sound like to you? It sounds like an engineered system. A good engineer will design a system with redundancies. The more important it is for the system to stay functional, the more redundancies the engineer will put in the system. Based on the latest genetic studies, genomes seem to be highly redundant systems that are best explained by design.

Comments

9 Responses to “Genetic Redundancy – An Amazing Design”
  1. Right in the abstract of the article in a real scientific journal: “My results demonstrate that interactions among unrelated genes are the major cause of robustness against mutations. This type of robustness is probably an evolved response of genetic networks to stabilizing selection.”

    So the researcher doing the original science thinks that evolution caused the robustness, not an “engineer”.

    And I noticed the Caveats section* in this paper immediately after your last quote from it. (second to last blockquote). Has there been any follow up research in the last ten years that has overcome these caveats and/or supported Dr. Borger’s interpretation of the results?

    “It sounds like an engineered system.” So you’re adding “sounds like” to “looks” and “seems” as major categories of evidence. Good for you.

    * Do creation scientists ever include Caveats sections?

  2. jlwile says:

    “So the researcher doing the original science thinks that evolution caused the robustness, not an “engineer”.”
    Of course, because the researcher is working from an evolutionary perspective. However, the more scientific analysis is provided by Dr. Borger.

    ““It sounds like an engineered system.” So you’re adding “sounds like” to “looks” and “seems” as major categories of evidence. Good for you.”
    Indeed, because this is what real scientists do. It says a lot about you that you don’t know this.

    “Has there been any follow up research in the last ten years that has overcome these caveats and/or supported Dr. Borger’s interpretation of the results?”
    Of course, and the research indicates that Dr. Borger’s interpretation is correct.

    “Do creation scientists ever include Caveats sections?”
    Of course. The fact that you don’t know this indicates a lot about your knowledge of origins science:

    Gogonasus—a fish with ‘human’ limbs?

    The superbaby mutation

    Estimating a Cell’s Contribution to Directed Mutation

    Radioisotopes and the Age of the Earth

  3. baraminology.blogspot.com: free
    “This blog has been superceded [sic], and is only here for archive purposes.”: priceless*

    * If the superseding blog wasn’t creationist. But, alas, it is.

    Are you going to the 2010 BSG/CGS Joint Conference?

  4. jlwile says:

    Once again, I would just like to point out how Shooter is doing what he usually ends up doing once he has been demonstrated to be horribly wrong in his comments. He is trying to distract by posting something irrelevant. Way to continue to follow your pattern, Shooter!

    I will not be attending the 2010 BSG/CGS Joint Conference. I haven’t been to any of them.

  5. My comment was about the third link in your list. I threw in a simple question that I found from that link. At least I’m asking questions. You don’t seem to be getting too many of those lately.

    How about this on the fourth link: RATE info from Answers in Creation.

    The second link, “The superbaby mutation” got my interest up, especially after reading the sub-title, “Evolution of a new master race?” But it’s only a couple of paragraphs about the no-new-information thing. A caveat in the footnotes, such as they are. BTW, good Googling to find those caveat examples.

    From the first link, I found these quotes:

    “One may think that with all the attention given to these fossils they constitute irrefutable evidence for evolution, thereby falsifying the biblical record of history.”

    “When one takes the time to look beyond the media parade at the actual evidence, it is clear that the claims are far less spectacular and do not in the slightest threaten the straightforward history of Genesis.”

    Do you believe Genesis is a straight-forward history?

  6. As for the research links, again a simple read of the first one’s abstract produces this:

    “Unlike in yeast, this phenomenon has not yet been analysed systematically in the mouse. In this review, we present examples of mouse knockouts that lend support to the concept of robustness, discuss the mechanisms by which it may have evolved, as well as speculate on the reasons for its evolution.”

    There’s that word, “evolution” again. The second is a letter that doesn’t seem to have improved on the caveats to the original paper discussed:

    “Because accurate temporal parameters are not yet available for many protein–protein inter- actions, we estimated temporal characteristics of hubs and their partners by using compilations of yeast messenger RNA expression profiling data.”

    The last link is to a short paper that is about “synthetic sick or lethal (SSL) partners” and thus off topic. The paper states: “However, even using a permissive definition of homology (BLAST E-value <10−3), only 2% of SSL gene pairs are paralogous."

    And it's paralogue.

  7. jlwile says:

    Shooter, you have repeatedly accused me of quoting people and articles in a deliberate attempt to mislead, but of course, I have demonstrated that I do not engage in such intellectually-dishonest activities. However, I have caught you doing that several times, and in this case, you do it TWICE in one comment. When attempting to comment on the studies that clearly support Dr. Borger’s analysis, you engage in dishonest quote-mining to make it look like the studies do not say what they are clearly saying. For example, you claim:

    The second is a letter that doesn’t seem to have improved on the caveats to the original paper discussed:

    “Because accurate temporal parameters are not yet available for many protein–protein inter- actions, we estimated temporal characteristics of hubs and their partners by using compilations of yeast messenger RNA expression profiling data.”

    However, this quote says NOTHING about caveats related to the data. In this part of the paper, the authors are discussing their MODEL and how they DEVELOPED it. These comments do not affect the conclusion of the paper, because they show that their model agrees well with the data. Of course, all this supports Dr. Borger’s analysis.

    In your second case of deliberate quote-mining and mischaracterization, you claim:

    The last link is to a short paper that is about “synthetic sick or lethal (SSL) partners” and thus off topic. “However, even using a permissive definition of homology (BLAST E-value <10−3), only 2% of SSL gene pairs are paralogous."

    Once again, this is completely false and a total mischaracterization of the paper. As the authors clearly state:

    A key indicator of a compensatory relationship is a synthetic sick or lethal (SSL) interaction, in which mutation of two genes in combination yields a more deleterious phenotype than either single mutation alone.

    Thus, they are using SSL’s as INDICATORS of compensatory relationships, like those of duplicate genes. Thus, this is not off topic, but directly related to the concept of genetic redundancy. Once again, their results clearly support Dr. Borger’s analysis.

    Now on to your other mistakes:

    “There’s that word, “evolution” again. ”
    Yes, and look at the word that accompanies it: SPECULATE. While the results are a direct confirmation of Dr. Borger’s analysis, evolutionists are forced to SPECULATE about how an evolutionary framework can accommodate them.

    “And it’s paralogue.”
    You clearly don’t read much science, do you?

    From your favorite source: “Paralogs typically have the same or similar function, but sometimes do not: due to lack of the original selective pressure upon one copy of the duplicated gene, this copy is free to mutate and acquire new functions.”

    From an article in the Oxford Journal Nucleic Acids Research: “EXOG, a novel paralog of Endonuclease G in higher eukaryotes”

    From the Journal of Molecular Evolution: “Gene Conversion Among Paralogs Results in Moderate False Detection of Positive Selection Using Likelihood Methods”

    If you spent any time educating yourself on science, you would know that there are multiple spellings of many scientific words, due to the interactions of many cultures in the process of science.

    “My comment was about the third link in your list. ”
    No, it was not. It was about a misspelling, which has nothing to do with the discussion at hand. Once again, you were simply trying to distract from the fact that your comments had been demonstrated to be 100% false.

    “At least I’m asking questions. You don’t seem to be getting too many of those lately.”
    True. I expect people are too entertained with you embarrassing yourself to ask many questions. I know that I find it hard to think of questions after laughing at the nonsense that you write.

    “Do you believe Genesis is a straight-forward history?”
    I don’t think that all of Genesis NEEDS to be taken as straight-forward history, but the evidence indicates that it is. While there are some good arguments for talking the first several chapters as poetry or allegory, I think that the bulk of science indicates that those chapters give a very good description of earth’s history.

  8. SLPage says:

    Borger, asthma researcher, has proposed what he calls the “Grand Unifying Thoery of Biology,” quite a lofty goal for someone with no recognized expertise or track record in the fields he proposes to revolutionize. But then, hyperbolic claims are part and parcel of the creationists’ bag of tricks, eh Dr,Wile?
    Borger has also claimed that mutations often occur so non-randopmly as to appear random. Brilliant insight. I first encountered Borger on a discussion forum about 7 years ago. Read how he tries to tell the author of a book that her book really supported HIS position, not the one the author says it did:

    http://www.evcforum.net/cgi-bin/dm.cgi?control=msg&t=1009

    See how Borger misrepresented himself at the TalkOrigins website:

    http://www.evcforum.net/cgi-bin/dm.cgi?control=msg&t=9043

    See how Borger jumps to ridiculous conclusions despite not even being able to grasp what the claims he is responding to are:

    http://www.evcforum.net/cgi-bin/dm.cgi?control=msg&t=9170

    Great partner in Creation Science to have, Jay. Keep it up!

  9. jlwile says:

    When people are forced to engage in character assassination instead of actually trying to discuss the issues, it simply illustrates the weakness of their case. Well done, SLPage!

    I do encourage people to read the links, as Dr. Borger does none of the things that SLPage accuses him of doing.

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