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Human Genome More Like a Functional Network
bshell writes "An article in science blog says we may have to rethink how genes work. So called "junk DNA" actually appears to be functional. What's more it works in a mysterious way involving multiple overlaps that seems to be connected in some sort of network." From the article:
"The ENCODE consortium's major findings include the discovery that the majority of DNA in the human genome is transcribed into functional molecules, called RNA, and that these transcripts extensively overlap one another. This broad pattern of transcription challenges the long-standing view that the human genome consists of a relatively small set of discrete genes, along with a vast amount of so-called junk DNA that is not biologically active.
The new data indicates the genome contains very little unused sequences and, in fact, is a complex, interwoven network. In this network, genes are just one of many types of DNA sequences that have a functional impact. "Our perspective of transcription and genes may have to evolve," the researchers state in their Nature paper, noting the network model of the genome "poses some interesting mechanistic questions" that have yet to be answered."
Its what we in the programming field would call the Data Segment.
They need to hire some Perl and 60's-style-COBOL programmers who know how to read tangled code ;-)
Table-ized A.I.
It's somewhat funny - I remember having this exact discussion with my genetics professor. I was a chem major who is now a developer.
... but perhaps I've just looked at too much dissassembler. I will feel a little vinticated if this is proven.
It seems to me that DNA/RNA is "machine code" and data which runs on the laws of nature. It's a layer removed from silicon design, more akin to a self-modifying FPGA.
In other words we're so far only looked at the boot code and associated data. The "program" is what we were calling junk.
And it makes sense - if you think of the program as a massive recursion network which builds common parts (stem cells) and then organizes and specializes.
I know that's a simple bastardization
I said no... but I missed and it came out yes.
Sigs are too short to say anything truly profound so read the above post instead.
I don't think evolution would be very kind to unneeded material.
There's really almost no selection pressure against extra DNA sequences, particularly ones with no associated promoter. One of the proofs of this is the fact that the human genome is comprised more of endogenous retroviruses than actual functional sequences.
I never have frustrations, the reason is, to wit:
If at first I don't succeed, I quit!
These scientists have probably been looking at cells running in the debugger...
I walk down the street and see 100s of people who appear to be predominantly junk DNA.
No one thinks that flight just popped into existence. There are all sorts of useful traits prior to actual full flight that the earliest flyers would have developed: heck, things like feathers pretty clearly evolved long before flight was even remotely possible, and likely for very different reasons than flight. As for the thing itself, there are lots of different adaptions and traits on the way to flight that are all useful: things like decreased weight for sprinting across the ground, and of course brief gliding from tree to tree without actually being able to fly.
I've always suspected that "junk DNA" was the key to micro-evolution and speciation. I read an article once about how bacteria that could not metabolize lactose were cultured in a lactose-rich liquid. After about 60 generations, some bacteria that could metabolize lactose appeared. It turns out, they had non-functional genes for metabolizing lactose in their junk DNA, and somehow those genes were re-activated.
He who lights his taper at mine, receives light without darkening me.
Why it was called junk before you'd ask? Because our definition of what is useful wasnt all that accurate.. just looking at so called open reading frames and declaring everything else to be junk does not work. There is also the problem with insertions in a gene sequence that are either not or alternatively used. There are plenty of sequences that are never translated (no proteins are made of it) BUT without them we would be missing a big chunk of regulators etc. 'Recent' findings like ribozymes, IRES elemtens, attenuation elements etc. are all not translated into a protein yet serve a very specific function. Some of this 'junk' also serves as a insulator / separator between various sequences. We may never be able to map every nucleotide to some function but declaring it junk from the get go was just looking to be proven wrong. Just look up NCBI and look for some good reviews on this topic ;)
Whenever I read something like this, I get a reminder how poor is biologists' comprehension of Computer Science, Information Theory, and languages.
Whenever I read a post like this, I get a reminder how poor is most techies' comprehension of biology, and more specifically, what biologists do.
Third, why this obsession with zeroing in on a magic gene that causes X? Do they think the language of DNA is context free? Defects could indeed be expected to have no context, but for the rest-- which genes determine a person's blood type? Eye color? Skin color? Going about that task by trying to find the magic gene for something like that is like a person who never learned to read trying to figure out the plot of a book by trying to recognize patterns of letters.
Okay, why do we care? Because finding the genes (note my use of the plural there) that influence certain traits is the first step toward understanding the overall processes that create them. Obviously this is most critical in the area of genetic disease, although it's interesting for everything else too. We've known for decades that most traits, including diseases, aren't controlled by a single "magic gene." What statistical geneticists try to do is find locations on the genome which have a strong relationship to the trait of interest. And we know perfectly well that there will be a whole bunch of these locations for most traits, and that some of them may represent genes and some may represent something else. The purpose is basically to give the wet-lab biologists something to zero in on.
Second, two of the examples you chose -- blood type and eye color -- are really terrible ones for your argument, because genetically speaking they're very simple traits (two or three loci each, IIRC) and, at least in the case of blood type, we know exactly where they are in the genome. Eye color I'm not sure about, and skin color is a little more complicated, but not a whole lot more so.
Please do not confuse the pop-sci "scientists seek gene for X" writeups with what really goes on in the world of genetic research. It has exactly as much to do with real science as TV portrayals of hackers have to do with real computing.
The correlation between ignorance of statistics and using "correlation is not causation" as an argument is close to 1.
We have this huge disk, and most of it is malware or free space. The results in RTFA are interesting, but the general idea that we can measure the frequency of changes and statistically determine whether evolution is working on a specific sequence, should still be sound, so if they are indeed used, it is probably in a far less sequence-sensitive context (sometimes overall folds, sometimes just stochastic effects from the whole pool of junk transcripts affecting the balance in the nucleus).
crashfrog, you may have to correct me, but here's a start...
/bin/perl and that's how it knows to start copying off DNA code. (While on the subject, just because it has #! /bin/perl doesn't mean it will get executed, and even after it's been executed it might get a SIGKILL.) Promoters are not just found in DNA, but read on wikipedia for more on that.
There's really almost no selection pressure against extra DNA sequences,
This refers to the process in evolution where an organism fails to reproduce due to having a disadvantage that the other critters in the species don't have. So if a pig that has useless DNA sequences tacked on in its genome has a statistically lower chance of having piglets, there's pressure against those useless DNA sequences.
crashfrog is saying that for a reason he explains (below) extra DNA isn't going to have any effect on the organism's chances of reproducing.
particularly ones with no associated promoter.
A promoter is a marker in the DNA strand. The protein "machine" (a transcription factor) that gets the "data" off the DNA and into the cell's outside chemistry has a "socket" that matches the "plug" formed by the specific pairs of the "promoter" marker. It's like the transcription factor searches for #!
One of the proofs of this is the fact that the human genome is comprised more of endogenous retroviruses than actual functional sequences.
I'm not sure if I can do this last sentence piece by piece, so here goes...
An endogeneous retrovirus is a kind of virus that infects DNA. So when the cell splits, the virus gets copied along with it. For instance, some scientists think Multiple Sclerosis is one of these retroviruses that has infected our DNA. So when we look at the entire human genome, all the pairs in the whole DNA sequence, and we look at where all the promoters are, it seems (according to current theory -- we may learn more about this!) at a first glance there are some pretty long stretches with no promoters. That is to say, they are either empty sectors on the disk, or some of them look like retrovirus DNA code.
How'd I do at explaining that? Like I said, crashfrog should probably amend my explanation...
Be careful here--you might just show your own ignorance. "Biologists" is a very broad term that covers a vast array of topics. Sure, ecology might not require much knowledge of computers and information theory, but such things are required reading for fields like molecular biology or modern genetics.
Not necessarily. Sure, that may be the case for single-celled organisms that rapidly reproduce, whose selective forces dictate sheer metabolic efficiency, but for multi-cellular organisms, like mammals, there's good reasons to believe that that simply isn't true.
Evolution isn't like a programmer. It isn't some transcendental force guiding a species to some aesthetically "perfect" design. The result of natural selection frequently isn't the "best" solution but rather whatever happens to work. In fact, many times adaptations based upon the selective pressures of the present are, in time, ultimately maladaptive for the species. A classic example of this is the trait for the disease sickle-cell anemia in humans which originally served to offer slight resistance to malaria but otherwise causes health problems and even death.
A more efficient genome doesn't necessarily mean greater fitness. Consider the following example. For a large multi-cellular organism, which do you think has more reproductive/survival significance: (1) a mutation that deletes a few bases of non-coding DNA OR (2) a mutation that brightens a metabolically-wasteful, colorful marking that attracts mates?
OR that they are mostly random. The current model of DNA/genetics states that most of the DNA in the human genome is non-coding, not (significantly) subject to evolution. As such, it gets shuffled around (i.e. randomized) during cross-over events and mutations. That being the case, one wouldn't expect it to be very redundant or compress very well.
In short, because that's what's easiest. A holistic approach to genomics research like you're describing is not currently technologically, academically or economically feasible for a myriad of reasons. The science just is not there yet.
As an aside, I suspect we'll start to see a more integrated approach to genomics once the relatively low-hanging fruit of the one-gene --> one-protein research lines are throughly covered. However, I wouldn't expect such things to happen in our lifetimes given the difficulty of that aforementioned task and the sheer profitability of more conventional approaches. But what do I know? I'm "just a biologist." =P
-Grym
For me, its an Occam's Razor thing.
If I find a pencil on the sidewalk, the most obvious thing is someone dropped it.
I see life, and am at awe of its complexity. I have to conclude something designed it. Jehovah - Yahweh - the name as I understand it is Hebrew meaning "to cause to be". The name of God. Fair enough.
My problem is finding God. I mean God. Not religion.
Religion is Man's doing. Even if it was done in the best of intentions. The Church has killed some fine scientists who had it right (Galileo and others). If God was really with the Church, somehow I think God would have let the religious leaders in on it before they went off and violently demonstrated their ignorance?
Their treatment of anyone questioning them leaves me to believe that their organizations exist to protect the political power of certain factions, and God is brought in only as a pretext for their authority.
These scientists are decoding the very work coded by God himself. (itself?). Its amazing to me God has seen fit ( here I am again anthropomorphizing him again ) for us to have the wisdom to disassemble our own OS.
If we ever get to the bottom of this, I feel we will have an even better understanding of the Glory of God - whoever or whatever He is.
Its something about the elegance of design I see which leads me to believe there has to be some force - some intelligence - far greater than I out there.
I don't know what it is but I am insanely drawn to it.
"Prove all things; hold fast that which is good." [KJV: I Thessalonians 5:21]