Opposable Thumbs and Upright Walking Caused By "Junk DNA"

quinnlynn writes "A group of research scientists at Yale discovered that the evolution of opposable thumbs and upright walking in humans is due to changes in the genome in the areas still classified as "junk DNA." Quoting: 'Results from a comparative analysis of the human, chimpanzee, rhesus macaque and other genomes reported in the journal Science suggest our evolution may have been driven not only by sequence changes in genes, but by changes in areas of the genome once thought of as "junk DNA." ... Researchers have long suspected changes in gene expression contributed to human evolution, but this had been difficult to study until recently because most of the sequences that control genes had not been identified. In the last several years, scientists have discovered that non-coding regions of the genome, far from being junk, contain thousands of regulatory elements that act as genetic "switches" to turn genes on or off.'" Yale has also recently completed sequencing the Trichoplax genome. Trichoplax has the simplest known animal genome, and it shares 80 percent of its genes (comprised of 98 million base pairs) with humanity. Professor Stephen Dellaporta was quoted saying, "We are [excited] to find that Trichoplax contains shared pathways and defined regulatory sequences that link these most primitive ancestors to higher animal species. The Trichoplax genome will serve as a type of 'Rosetta Stone' for understanding the origins of animal-specific pathways."

I for one ....

Sometimes these factoids scare the coffee out of me ...

... still unknown whether HACNS1 causes changes in gene expression in human limb development or whether HACNS1 would create human-like limb development if introduced directly into the genome of a mouse.

When shall we welcome our furry, opposable thumbed overlords. Could Douglas Adams had been right all along?

Furry overlords notwithstanding...

This is hardly new. It has been recognised for some time that so-called "junk" DNA is nothing of the sort, but is almost certainly associated with gene expression to some degree.

The cool thing here (and what, I hope, will keep me in a job for a while) is trying to work out how.

(The fun aspect of molecular biology is that so much changes even over the course of a 4-year degree course... - and to think I nearly went into maths, where I wouldn't be doing anything remotely cutting-edge until PhD level...)

Re:Furry overlords notwithstanding...

I would say it's more like 50 year old COBOL air traffic control program that's been patched thousands of times by different people. Nothing is where it should be or done the way it should be, no guidelines were followed, but somehow it still manages to compile because each incremental change was tested before patching the source tree. (Hopefully someone can convert this to a car analogy for me.)

Gee, maybe JUNK DNA is a dumb idea

I'd love to see the results of removing Junk DNA from a human's genome, and then pump it into an egg and grow it up all normal like and see what kind of walking cancer emerges.

Junk DNA doesn't exist. It's just DNA we don't understand.

RS

Re:Gee, maybe JUNK DNA is a dumb idea

'I'd love to see the results of removing Junk DNA from a human's genome, and then pump it into an egg and grow it up all normal like and see what kind of walking cancer emerges.'

Well, Nature has (sort of) done this experiment already. The Fugu (pufferfish) genome has a highly 'compressed' genome, with about the same number of genes as mammals, but a much smaller complement of non-coding DNA:

http://genomebiology.com/2002/3/9/comment/1012 [genomebiology.com]

So it's certainly possible for an 'advanced' species to survive without the 'burden' of much of this material (obviously the regulatory elements are still required, but a lot of the highly repetitive stuff seems to be dispensable). Of course the 'junk DNA' may still confer evolutionary advantages (as the linked article put it: 'it may in fact be the clay from which evolution fashions morphogenetic changes'), and perhaps it says something that mammals have in general evolved in what most of us would regard as a much more interesting way than pufferfish...

Re:Gee, maybe JUNK DNA is a dumb idea

I'd love to see the results of removing Junk DNA from a human's genome, and then pump it into an egg and grow it up all normal like and see what kind of walking cancer emerges.

Unless you also modified the host's DNA as well it might well do nothing. Chickens have genes for growing teeth and long tails, which are simply switched off.

Junk DNA doesn't exist. It's just DNA we don't understand.

Some of it probably is actually junk. Where DNA performs no function at all there is no evolutionary effect to weed out harmful mutations. Though it's possible that many mutations of an "obsolete" gene may result in something useful.
If DNA is observed which dosn't vary much between individuals (or even species) then that tends to imply that it functional (possibly even very important). Even if we currently have no idea what that function actually is.

DNA fingerprinting

In defense of DNA fingerprinting it is often stated that the databases only store non-coding DNA, so there is no risk that someone might be able to centrally deduce possible health problems and other traits which could negatively affect the individual. How does that argument hold up now?

Re:DNA fingerprinting

In defense of DNA fingerprinting it is often stated that the databases only store non-coding DNA, so there is no risk that someone might be able to centrally deduce possible health problems and other traits which could negatively affect the individual. How does that argument hold up now?

I'm not sure where the statement you're questioning came from, but my understanding of DNA fingerprint databases is that they don't actually store DNA base-pair sequences at all, but merely a list of the distances between certain marker sequences. Imagine taking a text document, counting the length of each paragraph, and summarising it by saying how many of each length there is. With long enough documents you're unlikely to find exact matches, but the numbers don't tell you anything actually useful about the contents of the file.

In other words...

In the last several years, scientists have discovered that non-coding regions of the genome, far from being junk, contain thousands of regulatory elements that act as genetic "switches" to turn genes on or off.

...Biologists discover "flags". Seriously, these guys should just bring a programmer on-staff — preferably assembly, as decoding the arcane secrets of all Earth life should be a breeze for anyone whose day job involves the x86 instruction set.

Re:In other words...

Biologists discover "flags". Seriously, these guys should just bring a programmer on-staff -- preferably assembly, as decoding the arcane secrets of all Earth life should be a breeze for anyone whose day job involves the x86 instruction set.

[Sigh] Every time a biology story is posted on /. it seems like we get a bunch of posts along the lines of "dumb biologists, any techie would have figured that out a long time ago!"

Please don't confuse the reality with the dumbed-down versions that appear in the popular press or the even more dumbed-down summaries. Bioinformatics, which is what I do, has been an established science for over a decade, and I can assure you that computer scientists have been working with biologists for a lot longer than that. Most of the obvious computational analogies have already been thought of -- and most, unfortunately, have had to be discarded. Despite some of the superficial similarities, genomes are not programs, at least not in the way CS people use the word. They're more like a collection of heuristics, and even that way of thinking about things breaks down when you start looking at the details.

I'm more on the CS/math/stat side of things, and my colleagues on the bio side are often mystified by what I do -- but I'm equally often mystified by what they do. Both CS and biology are tremendously complex fields, and if you think you can arbitrarily apply lessons learned from one field to the other, you will almost always turn out to be wrong. Biologists and computer scientists can learn a lot from working with each other; work in one field very often leads to advances in the other; and by all means (he says, with a healthy dollop of self-interest) the areas of collusion should continue to grow. But thinking that there's some natural equivalence in one field to what you know from the other is simply a mistake.

"Junk" DNA

I probably should have clarified in the post but "Junk" DNA is a misnomer though still the most commonly used term for the part of the human genome (over 90% of it) that we don't know the uses for. The word "junk" isn't used in the sense that the DNA there is worthless and should be discarded. More like a junk drawer. There's a bunch of stuff over there that doesn't seem to belong to anything but we know that a lot of it probably does, so scientists keep testing around in there to see what goes where.

DNA = Turing Machine Instructions

We'll eventually discover that DNA is just instruction tape for a type of turing machine which generates our entire body as its output. As we all know, Turing machines require lots of repetitive instructions to operate because they're so limited in their actions.

Finally.

I'm glad I can now scientifically justify why I like a little junk in the trunk.

Lovely...

Our DNA has a goddamn registry.

Re:Why not admit to ignorance?

I have always found it irksome when biologists claim that a high percentage of our DNA is just junk (do-nothing) DNA. It's as though they were saying "we of course know what it does: It does not do anything". Why not say "we don't know what it does, if anything at all"?

Most of them do, "Junk DNA" is a handy phrase and one that's been picked up by the media, the majority of Biologists are quite open minded on the subject. The fact that a lot of it is translated in to RNA even lends wait to the argument that it is of functional value. Aside from that things like telomeres (the ends of DNA that get eaten away as the replicates) and centomeres would be labelled as "junk" even though they have obvious functional value. Most scientists just use "junk" as a synonym for "non-protein coding" as a kind of shorthand.

Re:Just like the brain areas "you don't use"

Actually its been widely known that 'junk DNA' does have an active role for a long time. The big problem is identifying which bits of it are responsible for regulation/transcription.

The main problem with the public's perception, and indeed that of some scientists, is the continued use of the term 'junk DNA' when the concept it embodies has been thoroughly discredited.

For the moment a lot of work does discount area's of DNA for which there isn't enough background information, but that's more to do with the need to make progress on the bits we understand, rather than to avoid looking at the junk.

This is likely why so many people still think that Junk DNA is a thing that we actively avoid. It isn't.

Re:Just like the brain areas "you don't use"

Not exactly. We _know_ that a large part of DNA (about 40%) is junk, because it consists of simple repeating sequences (LINEs and SINEs).

It might have some indirect functions (like working as a buffer for mutations), but it's junk by itself.

There's also a fair amount of inactive genes and other junk.

Re:Just like the brain areas "you don't use"

Not exactly. We _know_ that a large part of DNA (about 40%) is junk, because it consists of simple repeating sequences (LINEs and SINEs).

It might have some indirect functions (like working as a buffer for mutations), but it's junk by itself.

There's also a fair amount of inactive genes and other junk.

No, we have no idea what a lot of it does, but its not junk, its just not fully understood. The term junk implies we know that it does nothing, but we do not know this for sure, and a lot of what we were sure was inactive now turns out to be active after all.

Also, we don't even know for sure if 'inactive' genes are really inactive or not. Its fiendishly hard to tell an 'active' gene from an 'inactive' one as it is. Inactive in this case meaning that it is sufficiently different in form from what we understand as being an active gene that we believe it may be one longer in use, or we haven't detected expression from it.

In fact there is no method currently capable of telling active genes from inactive ones with greater than 80/12 accuracy.

This means that when 80% of genes, in fact the promoter element, which is what we look for, have been correctly identified, 12% of DNA which is known not to be Genes have been incorrectly identified as being Genes.

And that's with labeled data that has been carefully prepared. Even allowing for labeling errors, that's not great accuracy, although its pretty good that we can do that well.

Applying the same technique to unlabeled DNA (such as a straight end to end search of someones DNA sequence), and its likely your level of accuracy will drop even more.

Re:Just like the brain areas "you don't use"

A strange thing happened, I removed the junk data ( sync preamble ) from my floppy disk encoding and it quit working. I agree that SINEs and LINEs are less of a factor than others but a system is responsive to all its parts and until somebody makes a human clone with all the short and long repeats removed I assume that it does something, even if it just makes a different sync preamble or a getter ( to use a radio tube analogy ) for other junk.

At an abstract philosophical level you have a point, but by the same token you wouldn't let a doctor remove a wart from your finger, because we can't be sure that the wart doesn't play some unknown role in maintaining health. Practically, quite a bit of evidence shows that warts play no significant role in maintaining health, and can be removed safely. There is a LOT of evidence that LINEs and SINEs are simply 'scars' left by a parasitic attack, much like a wart. Large segments of "junk" DNA have been removed from mice [bioedonline.org] with no apparent ill effect to them or their progeny.

Re:Just like the brain areas "you don't use"

Does it share 90% of schematics with Core 2?

Re:Just like the brain areas "you don't use"

You found out what 10% of the brain does (the sensory/motor areas)? The other 90% must not be used for anything.

This old myth actually never had its origin in science, but was created and then spread through popular media [washington.edu]. Please don't help it survive - it's time to let it die.

Re:Just like the brain areas "you don't use"

Somebody else is beating you up about the 10% brain issue (although when you deal with people on a regular basis it's not hard to believe that 99.9995% of a human's brain isn't used much), you Darwinism leads me to jump on you about another pet peeve of mine.

If Darwin was right about evolution, then all that DNA stuff has to be there for a reason.

Charles Darwin was amazingly right on the broader picture of speciation and evolution. Not surprisingly, he got some stuff wrong. But nowhere does ol' Charley - or any other serious tract on evolution - require the perfection that your statement implies.

Many people (biologists included) look at highly evolved structures (and by this I am specifically not including television producers) and wonder about the complexity and intricacy of it all and use these concepts as some sort of metric for perfection. Evolution doesn't require this at all. All you have to do to be successful is to produce more of you than dies off for whatever reason. If you carry large quantities of DNA (or adipose tissue or whatever) that doesn't do anything useful but doesn't do anything harmful, then that's OK. If said stuff is a selective disadvantage, then it's not so OK but it might not be a problem in terms of the ability to create progeny. Stuff doesn't have to be there for a "reason". It can be neutral or only mildly deleterious and the critter survives.

That said, it may be that these piles of repetitive sequences interspersed with sequences that used to code for something but currently don't create a gene product or are used as a control sequence, serve as evolutionary reservoir to get spliced and diced by random processes and eventually create something that does help the organism survive.

Evolution only requires that the organism muddle through better than some other organisms. It doesn't require perfection and grace.

Re:Just like the brain areas "you don't use"

I don't think that you understand the theory of evolution.

Evolution predicts that much junk will be generated during the process of evolution...and that it will be cleared away at a rate related to how expensive it is to continue it's existence. It also predicts that this will be a stochastic process.

At a more basic level the question becomes "What is the proper theoretical level to assign the role of replicator?" Traditionally this was considered to be either the individual animal or the population. Recently (20 years) strong arguments have been made that the proper level is the gene. This has been confirmed, though not proven, by the discovery of transposons and various other genetic elements that appear to act as parasitic genes. Also by virus genes embedded into the DNA that appear to have melded into the normal code to produce useful-to-the-organism genetic code, and others that do things like alter the sex ratios in a manner that facilitates their propagation of multiple copies.

It's hard to see what proof would be possible. Confirmation is offered by some predictions based on that theory being confirmed and on many other observations that are more simply explained by considering the genetic code itself as the level at which evolution is occurring.

One would think that genetic programming might offer some clues, and, indeed, it does. In genetic programming one of the big problems is clearing away junk genetic codes as the generation progress. I'm not current, but when I last checked this problem had not been solved satisfactorily.

Re:Just like the brain areas "you don't use"

I am no Biologist but I have often wondered at thew high levels of successful evolution mammals can do compared to the relatively slow levels that reptiles and insects seem to have.

I am a biologist, you've got that totally backwards (it's okay though, it's for counterintuitive reasons). By most evolutionary standards, the bugs own this planet. A famous geneticist named Haldane was asked once "knowing what you do about nature, what can you tell me about God?" He said "He has an inordinate fondness for beetles." They're incredibly diverse compared to mammals. Insects dramatically outnumber us and out breed us. And their evolution rate is extremely fast due to their extreme proliferation. Pioneering studies of genetics and evolution almost always involve Drosophila flies because you can get tens of thousands of generations in a research career (and genetic change to match that) wheras you could probably get at most two human generations and only hundreds of mice generations. As one last testament to the (evolutionary) superiority of insects: cockroaches have been here before we have and will undoubtedly survive after we have nuked ourselves off the planet, they might slow down for a generation, but they've far outspecialized mammals.

Keep in mind that evolution doesn't mean higher, smarter, faster, it just means more fit to their niche. A bigger brain has given us the power to make a civilization and big buildings, but evolutionary fitness is actually measured in how many offspring you have, since that's the goal ultimately in evolution, and bugs have us whipped there.

It would allow for much faster adaption if instead of reinventing new structures at random all our bodies had to do was express other "Junk" genes at random.

That is an accepted theory, one which the current results do support (I think, I haven't read the article.) It's also worth noting that plenty of times, non-junk DNA gets co-opted for different purposes. What appears to have happened fairly often is that a gene that's needed for something gets copied, so some organism has two functional copies of it, and then one is free to be changed slightly to different purposes. I don't know the statistics, but there are huge families of closely related genes which have different purposes but were at one point probably carbon copies that now do other things.

Re:Junk is as Junk does.

I don't understand it therefor it must be junk! Perfectly scientific.

Most scientists do not actually do this. Most reporters, on the other hand, do.