Posted on 03/29/2006 5:46:20 PM PST by DaveLoneRanger
Researchers develop new tool to find gene control regions
Researchers at the McKusick-Nathans Institute of Genetic Medicine at Johns Hopkins have invented a cost-effective and highly efficient way of analyzing what many have termed "junk" DNA and identified regions critical for controlling gene function. And they have found that these control regions from different species don't have to look alike to work alike.
The study will be published online at Science Express March 23.
The researchers developed a new system that uses zebrafish to test mammalian DNA and identify DNA sequences, known as enhancers, involved in turning on a gene. In studying RET, the major gene implicated in Hirschsprung disease and multiple endocrine neoplasia (MEN2), the team identified DNA sequences that can control RET but had not been identified using standard methods. Hirschsprung disease, also known as congenital megacolon, is a relatively common birth defect marked by bowel obstruction. MEN2 is an inherited predisposition to neuroendocrine cancers.
The notion that mutations in enhancers play a role in human disease progression has been difficult to confirm because usually enhancers are located in the 98 percent of the human genome that does not code for protein, termed non-coding DNA. Unlike DNA sequences that code for protein, non-coding DNA, sometimes referred to as "junk" DNA, follows few rules for organization and sequence patterns and therefore is more difficult to study.
"The difficulty with human genetic approaches to common disease is that we lack the power to precisely localize DNA sequences that are associated with disease, often leaving us immense stretches of DNA to look at," says one of the study's corresponding authors, Andy McCallion, Ph.D., an assistant professor in the McKusick-Nathans Institute. Most often one is limited to looking in the most obvious places, which may not yield the best results. "Until now," he says, "we've only been able to look under the lamplights for the car keys."
Traditionally, DNA sequences are thought to have to look similar to function similarly; this is how scientists identify genes in other species, a strategy best used for studying similar species. From an evolutionary standpoint, the last common ancestor of human and zebrafish lived more than 300 million years ago. Because DNA sequences in each species have changed over time, traditional methods of comparing DNA sequences between humans and zebrafish have failed to identify any potential enhancers around the RET gene because the DNA sequences differ too much.
That drove the Hopkins researchers to seek and develop this new system, by which virtually any DNA sequence can be tested for its ability to turn on a marker gene in zebrafish embryos. The system is a significant advance over current methods in this model species, allowing researchers to study more sequences in a shorter period of time. Using this, they identified several human enhancers able to control expression consistent with the zebrafish ret gene.
Zebrafish have become the ideal system for doing these types of large scale studies. They are small - only about a half inch in length - they grow quickly, and are relatively inexpensive to maintain compared to mice or rats. "Zebrafish are the only vertebrate embryo you can even think about doing this type of work in," says Shannon Fisher, M.D., Ph.D., the study's first author and an assistant professor in cell biology in Johns Hopkins' Institute for Basic Biomedical Sciences.
The researchers' next steps are further study of the RET enhancers they found to identify other mutations that might contribute to Hirschsprung disease and MEN2, and to entice other investigators to collectively build a database of human enhancers. "If there's one thing we've learned here, it's that we are not very good at recognizing enhancers. We just don't know what they look like," says Fisher. "We are anxious for others to use this technology on their favorite genes."
Wikipedia claims junk DNA "is probably an evolutionary artifact that serves no present-day purpose."
Of course, "junk DNA" and "no present-day purpose" really mean "we don't know what function some DNA serves, so we'll call it junk DNA for now."
This ignorance is what led to saying the appendix is useless, or tonsils. (See: Do any vestigial organs exist in humans?)
As science progresses, new functions are being discovered for this "junk" DNA, and evolutionists are having to eat crow.
See also:
‘Junk’ DNA: evolutionary discards or God’s tools?
DNA: marvelous messages or mostly mess?
UCSD Study Shows 'Junk' DNA Has Evolutionary Importance
'Junk' throws up precious secret
(( ping ))
Who ever said that tonsils are useless or vestigal? I've never heard that.
"Such large returns of conjecture from such small investment of fact"
Gracias.
If we ever get to the point of being able to accurately manipulate genes, would it be then possible to slip someone like Alec Baldwin a "gene pill" so he grows a penis on his head?
dna ping
You mean another one?
Alot of doctors used to believe that, its why removing tonsils was so popular for so many years.
I lucked out, my doctor (while being arrogant) was right in his point that if it was useless, then it wouldn't be there, and told my mother the other doctors were just idiots for always removing them.
“In studying RET, the major gene implicated in Hirschsprung disease and multiple endocrine neoplasia (MEN2), the team identified DNA sequences that can control RET but had not been identified using standard methods. Hirschsprung disease, also known as congenital megacolon, is a relatively common birth defect marked by bowel obstruction.”
Will they claim this is the “gay gene” now???
Really... I saw someone the other day here on FR (one of the usual suspects) allude to “junk DNA” as having something to do with homosexual perversions.
Bill Clinton was trying to win the Stanley Cup in tonsil hockey!
The paper was written by members of the scientific community.
If they don't know what they're talking about, then nothing was shown.
Elementary logic is your friend.
Some non-coding DNA clearly does have a purpose. Some equally clearly does not. Finding a purpose for 0.001% of it doesn't really do much to change the picture.
Whether there's a lot or a little noncoding DNA has little effect on whether evolution is true or not. DNA sequences have their utility (coding sequences a GREAT utility, most noncoding sequences not so much), but DNA also exerts a cost. Just what those costs & benefits are will depend on the species, and could fall anywhere along the spectrum from strongly favoring no noncoding DNA to allowing vast amounts of the stuff.
Nature. 2004 Oct 21;431(7011):988-93. Related Articles, LinksMegabase deletions of gene deserts result in viable mice.
Nobrega MA, Zhu Y, Plajzer-Frick I, Afzal V, Rubin EM.
DOE Joint Genome Institute Walnut Creek, California 94598, USA.
The functional importance of the roughly 98% of mammalian genomes not corresponding to protein coding sequences remains largely undetermined. Here we show that some large-scale deletions of the non-coding DNA referred to as gene deserts can be well tolerated by an organism. We deleted two large non-coding intervals, 1,511 kilobases and 845 kilobases in length, from the mouse genome. Viable mice homozygous for the deletions were generated and were indistinguishable from wild-type littermates with regard to morphology, reproductive fitness, growth, longevity and a variety of parameters assaying general homeostasis. Further detailed analysis of the expression of multiple genes bracketing the deletions revealed only minor expression differences in homozygous deletion and wild-type mice. Together, the two deleted segments harbour 1,243 non-coding sequences conserved between humans and rodents (more than 100 base pairs, 70% identity). Some of the deleted sequences might encode for functions unidentified in our screen; nonetheless, these studies further support the existence of potentially 'disposable DNA' in the genomes of mammals.
That's interesting. They removed 2.3 megabases, which sounds impressive, but it's only one tenth of one percent of the mouse genome.
However, on the ID hypothesis, *I'd* think there would be *no* unused DNA.
But until we can get a better description of the hypothetical designer's abilities and aims and so forth, no-one knows what to expect from the ID hypothesis.
Of course, "junk DNA" and "no present-day purpose" really mean "we don't know what function some DNA serves, so we'll call it junk DNA for now."
IOW, scientists haven't even begun to scratch the surface of what genetics is really all about.
All the doctors who used to remove them from kids as routine tonsillectomies years ago. It was when someone finally figured out they were there for a purpose that they quit taking them out unless it was needed.
He'd like that.
MM: IOW, scientists haven't even begun to scratch the surface of what genetics is really all about.
There are some interesting results, though. Something I've always found rather fascinating is the Fugu (Pufferfish) genome.
...the fugu genome is only 390 Mb, about one-eighth the size of the human genome, yet it contains a similar repertoire of genes to humans (Brenner et al., Nature 366:265-268, 1993)....
Here's a Science and sensibility (a blogger)'s take on it
So what makes Fugu's genome such a great model of our own? First, it is approximately seven and a half times smaller than our own and it was thought that, being a vertebrate, it would hold a total number of genes similar to our own genome.Perhaps more importantly Fugu's genome contains very little so called repetitive DNA. Over half of your genome is made from small sequences of DNA repeated thousands or even millions of times, Fugu by comparison has 15% of its genome made from repetitive sequences.. The quickest way to sequence a genome is to sequence enough small stretches of DNA that you get a lot of overlapping sequences and all the fragments can be put together like a jigsaw puzzle.
To extend the jigsaw analogy repetitive sequences are like sky, hundreds of identically cut pieces of sky. Since they are all exactly the same it makes joining up overlapping sequences nearly impossible and since Fugu has less repetitive DNA it was easier to piece together the overlapping sequences.
The Fugu genome is now more or less completely sequenced and it has proved to be remarkably valuable tool. Fugu is effectively a "readers digest" version of the human genome - all the essential information with very little of the excessive baroque passages that litter our own DNA.
As well as the repetitive DNA mentioned earlier eukaryotic genes tend to contain large sections of DNA called introns that are never translated into proteins. In mammals these introns often account for more DNA that the actual coding sections of a gene.
The position of introns in genes is highly conserved between Fugu and human but the Fugu ones are routinely twenty times smaller. Additionally the space between genes is greatly reduced. Also 75% of the genes predicted from the human genome project are shared with Fugu
[extra paragraph breaks added]
This sounds like pretty significant research to me. What exactly do you think is wrong with it?
What are you talking about? You think these researchers aren't "evolutionists"?
[tonsils]
I was told (IIRC, it was a while ago!) that they were useful, but that it was better to remove them if they were getting infected all the time. The downside of leaving them in being strep throats and so forth.
Still have mine, had tonsilitis about 5 years ago (I'm 58)
Oh, well, I'm sure it's better to leave 'em in. Especially now that we have antibiotics.
A good example of a vestigial organ is wisdom teeth. These are, in fact, slowly being eliminated by good old natural selection:
Occasionally, someone will die from an impacted wisdom tooth getting infected. This can happen where there's modern dentistry, but is commoner in less developed places.
If he dies before having children, ...
It's slow, and we're slowing it down, but if there were some meaningful way to bet on things a million years in the future, I'd put my money on people not having them.
forgot to ping you
Some non-coding DNA clearly does have a purpose. Some equally clearly does not.That you know of, you mean. By the way, never heard back from you regarding my last post to you. Was that you "letting me have the last word"? It looks like you're avoiding. I'm sure you're not, but that's how it looks.
I had two wisdom teeth, both were impacted, were horribly painful, and made me miserable..I had to have both of them removed when I was in high school...My best girlfriend had all 4 wisdom teeth,and all four were impacted...she had them removed, 2 one time, and 2 at another time...she was also miserable...
Now my husband never had any wisdom teeth...and neither one of my boys ever had wisdom teeth...and hopefully no grandchildren of mine(should I ever have any), will ever have to deal with impacted wisdom teeth...they are horrible...
One time an anti-evolutionist tried to tell me, that wisdom teeth were not vestigial, because they could be used if your teeth further front in the mouth fell out, then all the other teeth would move forward, and the wisdom teeth would then grow through...seems like a rather contorted made up idea making absolutely no sense...just an attempt to counter the idea that there really are vestigial organs...
Would you want someone Muntzing with your childs DNA? didn't think so.
Except that if scientists were wrong about the .001% they could be wrong about the rest, too. There's also the aspect that it appears that scientists are looking solely at the physical, mechanical (as it were) effects that DNA has on the human body. How are we to know what affect the DNA has on the aspects of human beings that connot be measured, such as self-consciousness, emotions, etc? The non-physical part of the human. As far as I've ever heard, scientists still haven't figured out what makes a human think and reason, have self-awareness, morals, emotions, apprectiation of beauty, empathy, etc... I don't know of any evolutionary purpose for some of those things, like what an appreciation for beauty, art, music, would have for survival. Why would they have developed? DNA could control some of those things and we wouldn't even have a clue yet.
[Muntz TVs]
irreducible complexity
No, but that's the usual nomencature; vestigial structure or something like that might be better
What is your theory on why they will slowly die out? Were our mouths once bigger than they are now?
I explained it above; they can kill people; AndysAndMikesMom could nave been on holiday in, say, Siberia or the Outback and died of infection.
Yes the average size of mouth has been decreasing; look at the display of evolutionary skulls (Post 75).
? Are mine not a problem because I have a big mouth? (don't answer that one!)
OK
This is an example of where scientists lose credibility with the general public. They make blanket statements about things that are not well understood and then a short time later, have to revise or retract what they said. When this happens often enough, people get skeptical and stop believing what is announced.
Actually, that happened to me. I lost a couple of molars to decay and my teeth shifted forward and those wisdom teeth that came in behind there never gave me any trouble. The ones where I had all the molars did and I had to have them out.
Certainly it can happen that when one loses some teeth the other teeth can shift...the point to me tho, is this what wisdom teeth were meant for?.....I dont think that is their original purpose....most people do not lose their other teeth, at the age, where the wisdom teeth begin to try to erupt....for me and my girlfriend our wisdom teeth tried to erupt when we were in high school, for others, the teeth try to erupt a little later...but usually teenagers and those in their early 20s still have their molars, and its at that age that the wisdom teeth try to erupt...if they get badly infected, that could become a life-threatening situation...fortunately with modern dentistry, this is not a problem...
But having wisdom teeth to make up for other teeth that are lost is only an added benefit perhaps...but I just dont see it as being a reason for having wisdom teeth in the first place...
It should have quite a lot of effect. The ratio of "junk" DNA to normal DNA can be a very effective fudge factor to fit three sets of data which may not match otherwise, the fossil record and the estimated dates of the the branches between species, the genetic variance between those same species, and the rates of mutation that can be accomplished by species using natural selection.
The fossil record gives us an upper limit on the amount of time organisms split down two different branches. The rates of mutation of living species can be measured. If the difference in the DNA between two descendent species is to great to be bridged in the amount of time given by the fossil record, a fudge factor can be declared that a percentage of the DNA simply doesn't count. By finding "fitness" uses for DNA previously considered junk, scientists are gradually filling in the fudge factor, possibly until the fossil record and the DNA difference of particular descendants can no longer be explained by natural selection.
No, they found a purpose for a small part of it.
Reread the excerpts that Jennyp and I posted above. Jenny's had 2 million base-pairs removed from mice with no detectable damage at all. I don't know how many generations they've been through now.
The one I posted said that half our (and general mammalian) genome is composed of simple repeats. It also said another vertebrate can get by on one eighth the DNA.
It really does seem that a lot of it isn't used for anything.
This is an example of where scientists lose credibility with the general public.
Not really. If the initial estimate is 98%, and later research shows it's more like 95% or even 90%, very few people will even be aware of the change, and the great bulk of those who are won't consider it significant. There will always be people looking for an excuse to bash science, and to them any change in any previously-accepted hypothesis will do.
Perhaps the duplication of genetic material is just a failsafe to allow continuation of a species when a chunk of DNA is damaged, Or that the same change would have to happen in the identical strands to make a permanent change in the species. Just like if there were several computers running something, the extras are backups and self correcting mechanisms.
Although there was no detectable damage, I presume that was physically as far as defects or mutations. There has to be something controlling thought processes and consciousness and if it isn't DNA, then what is it? And if it is, then there would be no way of knowing what non-detectable changes might occur. Since mice can't communicate we couldn't know. The only real way of finding out is by doing it on people and THAT'S a scary thought.
On that note, I'm calling it a night.
Obvious example: mouse fur. A "furry" mutation would not survive in a hot climate, but come the next ice age, turning on a furriness gene might be the key to survival of the species. Tough luck if the gene that turned on furriness was one that we deleted.
I agree with other posters - we know hardly anything of how genes work, and we have decades (at least) of learning ahead of us. That's why I am opposed to GM organisms - we are meddling with a very complex mechanism in almost 99% ignorance.
Really!? I remember someone touting junk DNA as evidence of evolution. I think you might notice a difference between the words "junk" and "disposable". Scalpels are disposable.
See jennyp's post. If it can be removed with no discernable ill consequence, the probability is high it has no function.
Was that you "letting me have the last word"? It looks like you're avoiding. I'm sure you're not, but that's how it looks.
No, unlike B O'R, when I give someone the last word, I mean it. We know each others' issues. Evidently netiher of us feels they're worth acting on. The only rational thing to do then is to drop it.
Did anyone say definitively that this sequence had no function?
It is true that scientists intitially focussed on coding sequences and genes, and that agenic mechanisms of regulation weren't discovered until later. I don't think you could definitively show a sequence was junk unless you could delete it without consequence. But, as jennyp posted, there are big chunks of DNA that can be delected apparentkly without consequence. There are also transposable elements that are largely (note caveat!) without function; they appear to be genetic parasites. There is junk DNA, it's just a question of how much.
I fiond it amusing there are people who don't so science, whose occupation in life seems to be crowing when scientists make a mistake. I've seen this in other fields; there are always guys at a baseball game whose only delight is when someone makes an error. Schadenfreude isn't an attractive trait.
It might, but it doesn't. I have my wisdom teeth; I'm also missing one of my molars. The teeth haven't grown forward.
A quick look at the anatomy of the human jaw will show you why.
Another one of those dizzying moments when a YEer is this close to the truth. . . Evolutionary theory would in fact predict emerging functions for junk DNA. In all the junk DNA that accumulates through various mechanisms there is a lot of variation, and mutation occurs, and variation plus mutation is acted upon by natural selection to produce novel and unexpected functions.
Sometimes segments of the genome including genes do get duplicated. If this happens and there is a lot of that gene product needed evolution will favor the eventual emergence of a whole series of genes for this product, like the genes for ribosomes. If only a bit of the gene product is needed, the duplicate is then free to mutate and natural selection can drive a divergence between the two genes so that you get two specialized gene products fulfilling the need that was met before by a single ancestor gene product. This is what we've seen with the hemoglobin family or HOX genes. Other times a mutation kills the duplicated gene, converting it into a pseudogene, which typically is not transcribed. Usually these are relics in the genome that are not active and are only valuable to science for their use in tracing genetic phylogenies. Occasionally you'll find a pseudogene that is transcribed into RNA, but not processed into a protein. Most of these transcribed pseudogenes don't "do" anything--the RNA is degraded. However, some of them are fortuitously able to interact with the parent gene and regulate its transcription in a variety of ways.
Another example of non-coding but non-junk DNA is the palindromic sequences on the Y chromosome accumulated during its evolution. The Y chromosome is incapable of recombining with the X chromosome except at the tip, a pseudoautosomal region. Non-recombining chromosomes have a tendency to deteriorate with time as mutations build up and deletions occur. This is known as Muller's ratchet. Part of the Y chromosome's sequence is a reverse copy of important regions. The Y chromosome so far has escaped the ratchet by essentially recombining with itself. There's no guarantee for its long-term survival, though--one species of mole vole has dispensed with the Y chromosome altogether!
A final example of how junk DNA may not be junk DNA is that the three-dimensional shape of the chromosome can be important in gene transcription. A certain length of DNA may be useful between two chromosome regions for optimal transcription of these genes. Perhaps the DNA copes all right with a shorter segment in between, but when a retrotransposon (perhaps the fossil of an ancient virus?) splices itself in between these two regions and gives the chromosome some extra flexibility that aids transcription and makes the organism even more effective.
I expect we will find in future more adapted functions for junk DNA, although much of it will not yet have acquired a function.
My, my, the Lord has encrypted his anti-evolution firmware to confound the evo-hackers...
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