DNA 'Knockouts' Reveal Genes Humans Don't Need (sciencemag.org)

sciencehabit writes: Although humans have about 20,000 genes, exactly what most of them do inside our body's cells is still murky. One way to learn more is to find people who lack a working copy of a particular gene and see how that affects their health. Such so-called knockouts are scarce in the general population. But a new study points to a more efficient way to find them: Search the DNA of people from a culture in which marrying a relative is common. The study has found a number of genes that we seemingly can do without, including those thought to prevent serious diseases. And one healthy mother completely lacked a gene called PRDM9 that is involved in shuffling chromosomes during the formation of eggs and sperm. Mice lacking the gene are sterile.

Comments

Sphagetti code

[sinij]

Our genome is spaghetti code of the worst kind. If God exists, he is horrible coder.

Re:Sphagetti code

[Wycliffe]

Our genome is spaghetti code of the worst kind. If God exists, he is horrible coder.

Looking at the genome (or our brain) to understand how it works is kindof like looking at the end result of a neural net or genetic algorithm. The millions of random mutations get the right result based on the selection criteria (in this case survival). The animal world has plenty of extreme macroscopic examples of this whether it is extremely painful reproduction, deadly reproduction, insane impractical appendages, it doesn't really matter as long as your generation "wins". Some AI scientists have tried to reverse engineer relatively simple code generated by genetic algorithms and have found stuff that as far as they can tell shouldn't even work but exploits some small loophole in either the code, the hardware, or the selection criteria. When I was in HS, I did some GA stuff that failed miserably at midnight because the bots were taking advantage of minor variations in the random number generator and those assumptions failed as soon as the day changed. Our genome is this times a million. The number of flukes, switchbacks, random hacks, and things that shouldn't work but manage to because of some other random mutation is probably mind-boggling.

Re:Sphagetti code

[zx75]

Are you kidding? Considering that god wrote a program that is self-modifying, evolutionary, infinitely adaptable, and capable of self-reflection and consciousness from a few basic parameters that started the size of an infinitesimal speck containing all the energy in the universe... I would say god is an uncomprehendingly amazing coder!

Re:Sphagetti code

[PvtVoid]

Horrible from a human perspective. He is transcendent, we are just too dumb to understand the inner beauty.

That's what I tell people about my code all the time.

Re:Sphagetti code

[Zeio]

NO.

Its called epigenetics and three dimension conformation and methylation groups.

Gene expression relies on both methylation, epigenetics (inheritable - this is big as experience and environment can create gene expression changes that are passed to offspring) and three dimensional configuration of "useless genes" have an effect on gene expression.

Your notion of double helix and guanine tyrosine adensosine cytosine and uracil for thymine in RNA being simple "code" is absurd, disproved and ridiculous.

Removal of ""useless"" codons WILL change gene expression and cause huge problems which are not able to be predicted.

I noticed that most of the domain specific jargon words I'm using aren't showing up as known in Chrome so the world is not, according to the bulk data spell correction, even thinking about this issue of methylation, epigenetics and DNA codons and gene expression correctly.

Re:Sphagetti code

[Tablizer]

Our genome is spaghetti code of the worst kind. If God exists, he is horrible coder.

It's been obfuscated for security. He/she doesn't want humans mucking with it.

Re:Sphagetti code

[Notorious G]

Our genome is spaghetti code of the worst kind. If God exists, he is horrible coder.

Unless your your god is the flying spaghetti monster.

Oh man, you just blew my mind.

Re:Sphagetti code

[PvtVoid]

Well, some people *think* they know that God does not exist. They have about the same amount of proof as those who *think* they know that God does exist.

I also think I know that there are no invisible penguins in my dishwasher. And I have exactly the same amount of proof.

Re:Sphagetti code

[HiThere]

While there's some truth in what you say, there's not much. Epigenetics are rather like state variables, Methylation is analogous to a read-protect and de-methylation to the removal of such protections. Most epigenetic markers are removed between generations, but some slip through, an don't know the reasons. (That's not my area of expertise, but I believe that nobody currently knows why.)

OTOH, "unused" genes may be needed as spacers, as some enzymes depend on a particular separation between the pieces that they are attaching to. But many of them are flexible enough that removing the spacers wouldn't cause problems.

To say that the chromosomes are just strings of nucleotides would, indeed, be foolish. This doesn't mean that code isn't a good, even an excellent, analogy. It's the best analogy we really understand unless you want to consider it as being like a virtual machine, but few people really understand virtual machines. I suppose you could analogize it to a complex multiprocessor program with inter-process communication, but that doesn't really help ANYONE understand it. It's more accurate, but too complex and not sufficiently specific.

Removal of SOME "useless" codons will change gene expression. Removal of other "useless" codons will have no effect. Removal of other "useless" codons will have no effect except in the presence of particular external threats.

Remember, the genetic environment, including the code, evolved, which means that there's a lot of noise in the code. One of the problems of writing genetic programs is limiting the accumulation of noise in the code. Darwinian evolution does this by multiple means, but one of the primary ones is killing off the unfit before they can reproduce. This is difficult unless you're dealing with a really large population. Say the world population of mice. Larger animals with smaller populations have a tendency to go extinct. (Well, every species has a tendency to go extinct, but small populations are more likely to do so.)

Because of this humans are at two or three evolutionary disadvantages. We've expanded from a small population, so our genetic variability is small. We are a large animal, so we have a small population. And we avoid killing off the unfit. Genetic medicine offers an eventual solution. We aren't there yet, but this study is one of many needed stepping stones.

Re:Sphagetti code

[vivian]

We probably could eventually optimise our genetic code for our current conditions and environment - however there is probably a lot of 'unused' code that then gets turned on when envronmental conditions change or different stresses are introduced, making it possible for us as a species to rapidly evolve into something more able to survive, so removing al that 'useless' code would most likely turn out to be a big mistake when we one day discover that actually a lot of those unused genes would have been really useful after all, now conditions have changed.

Re:Sphagetti code

[Grishnakh]

Basically, we're just a bunch of Rube Goldberg machines.

Re:Sphagetti code

[HiThere]

Well, you could nominate the ribosome as a multi-processor CPU, but the analogy is really too loose to carry that far.

You don't use an analogy to get a detailed understanding of something, only to get a rough idea. For detailed understanding you need to study the thing itself. Like this study.

Re:Sphagetti code

[HiThere]

If you think many people understand virtual machines, then you are using the word "understanding" in a very different way than I do. Many people have a rough idea of how virtual machines work. That's not at all the same statement.

And as for your last paragraph, I think your acquaintance with code is shallow. Error Correcting Codes are common. Many of them can even correct multi-bit errors. Computer "viruses" modify existing code, but they were developed from programs that self-modified.

As for my level of expertise, it's only general science level WRT biology. I am aware, however, of the features that you describe, and so what. Do you expect analogies to be the same as isomorphisms? The better criticism of the analogy would be that code isn't self-motivated, doesn't build the environment within which it lives, etc. And even to that I say "So what?". The statement may be valid, but it's not a criticism of the analogy. If you're interested in that set of features you need a different analogy, but you won't find one that's perfect in all details, because that's not what an analogy is.

value of the "million genome project"

[peter303]

I heard there are between 10 and 20 thousand human genomes fully sequenced now. Both Craig Venter and Obama are trying to jack that up to a million. Then Analytics will replace a lot of painstaking lab work. (but not all)

Re:value of the "million genome project"

[sinij]

Next combine this with metadata gathered by NSA, and we could know exactly whom to show penis enlargement adds.

In other news

[Robyrt]

Studies reveal that humans are also able to survive without a functioning X-Gene.

Then again

[choke]

You can remove half the parts of my diesel engine. It'll work .. until the set of conditions that the specific part is intended to address occur at which time it will fail. Sometimes dramatically.

The human system is significantly more complex than my diesel engine, and the set of conditions that it encounters are significantly more complex as well.

The thought that ignorance of fact is evidence of fact is appalling. That we don't know what a part does, in no way indicates anything other than our own lack of understanding.

Plot twist

[wardrich86]

Plot twist: The genomes they lack are the ones that keep the rest of us from wanting to marry our siblings and cousins. Could this be the beginning of the end?

Defense in-depth

[ThatsNotPudding]

What one fool would call 'junk DNA', the ox-slow grinding of disease and toxins would call a chance for a few members of the species to survive a near-extinction event.

Re:So

[iggymanz]

Reptillian DNA studies wouldn't be relevant to us humans though

there is a lot we don't need

[Gravis Zero]

there is a lot of DNA that encodes for stuff we don't need... until we do. you could remove lots of genes that are only active under certain conditions if you can be sure you will never meet those conditions. however, the optimal evolutionary pattern is to hedge your bets.

Re:there is a lot we don't need

[Dr. Bombay]

Exactly. Just like you don't need a seat belt to drive a car.
The parameter space that can be easily probed is too small to say for certain that a gene is not needed.

Jumping to conclusions?

[kheldan]

I'm under the impression that much (if not all) of the so-called 'junk DNA' that seemingly does nothing, is more like 'error handling' or 'conditional' code that rarely, if ever, gets activated -- but that might save our lives. For instance, a recent Slashdot story: Viral 'Fossils' In Our DNA May Help Us Fight Infection

interesting but not quite what you think

[ooloorie]

Most of our genes don't do much of anything most of the time. But that's true of many things in our environment. Car analogy? I can sabotage your headlights, your seat belts, your rear seats, your locks, your airbags, your dome lights, your climate control, your emission filters and catalytic converter and... you might not even notice until months later. That doesn't mean that those items don't have any function.

In fact, large numbers of genes probably exist only to be used when you are sick or environmentally stressed. Many other genes give you redundant functionality, or functionality that individually only increases your performance on some task a little bit. Many genes have significant effects only in the brain, where it is very hard to find differences.

Don't get me wrong: the information that some gene can be deleted without being lethal is useful information. But it doesn't mean that you "don't need them".

Spaghetti code need not be a factor

[VernonNemitz]

"one healthy mother completely lacked a gene called PRDM9 that is involved in shuffling chromosomes during the formation of eggs and sperm. Mice lacking the gene are sterile."
The researchers might need to take another look at that woman; she might be a "chimera", whose reproductive organs don't have the same DNA as the part of the body responsible for a more-easily-tested substance (usually blood or saliva).

Re:Mmmmh

[drinkypoo]

" Search the DNA of people from a culture in which marrying a relative is common"
Kansas?

No, they said culture