I have a question.

[conuly]

Okay. So, let's say you're looking at your average pea plant. And, following the rules of genetics as set out by Mendel, we know that if it's got one recessive gene for a trait, and one dominant gene for that same trait, the dominant one is the one we'll see.

Now, I'll interrupt a second and say that bio was never my subject. Chem was easy, and physics was a blast, but I only got through bio (the third time. Time one was a flop, and time two... well, I passed the tests, but I still wasn't able to really do the work) by memorizing a bunch of facts that didn't make much sense to me. (They made more sense once I took chem, and more again when I took physics. We teach high school science backwards.) So you'll correct me if I say anything devastatingly wrong.

Now, as I understand it, your chromosomes themselves just consist of a small number of nucleotides. So what makes a specific combination of nucleotides say "make this pea green" or "this one's gonna be a yellow pea" or even (in the case of extreme manipulation or random mutation) "purple all the way"?

For that matter, how does a pretty small difference in DNA make me a human, and outside we've got daisies? Or even a huge difference, every little detail different, how does it work to make things? How does it make sense?

I never understood that point. I just threw it back up on the tests, whatever I needed to know (the second and third years. The first year was a loss completely), and I've forgotten a lot of it, since I didn't really learn it properly the first (three) time(s) around.

Comments

Mysteries de los mysterios!

[marveen.livejournal.com]

I probably butchered the spanish there, but it's my understanding that scientists are working doggedly on figuring out exactly HOW it is that a sequence of G-T-A-C etc. can convey the information that codes to "red hair/freckles/green eyes with brown specks/sparse eyebrows/pointed chin".

(I'll also point out that plants have RNA, we have DNA. One of those small differences, like polarity, that turns out to be vital.)

I suppose the DNA mystery is much like the way the computer codes its screen colors (yours show up as a banana yellow, burnt orange trim, with grey links) using only the on/off switches.

[hopefulnebula]

One of my uncles says the same thing about high school science. It makes a lot of sense.

Re: Mysteries de los mysterios!

[appadil.livejournal.com]

(I'll also point out that plants have RNA, we have DNA. One of those small differences, like polarity, that turns out to be vital.)

I'm sorry, but that's completely inaccurate. Plants (and indeed, all known living things if you don't think of viruses as properly 'alive') use DNA for their genetic code. RNA is used to help translate RNA into protein, and is also used as the genetic code by most (but not all) viruses.

Re: Mysteries de los mysterios!

[appadil.livejournal.com]

...damn. That should be "translate DNA into protein."

[siderea]

I know this one!

I'm going to oversimplify like mad, and then, if you want to inquire further, I may back up and desimplify as necessary.

Now, as I understand it, your chromosomes themselves just consist of a small number of nucleotides. So what makes a specific combination of nucleotides say "make this pea green" or "this one's gonna be a yellow pea" or even (in the case of extreme manipulation or random mutation) "purple all the way"?

First, let's ask what makes the greenness and yellowness in peas. Well, we know that. The greenness is chlorophyl, a chemical. The yellowness is, er, the natural color of the cell walls I think. Whatever.

Think also for a moment about skin color. What makes skin color? Melanin. A chemical.

What the specific combination of nucleotides control is the production of chemicals.

So now the question is "how do you get from a combination of nucleotides to different chemicals in different amounts?"

THe answer to that is "RNA Transcription" and it's way cool and very hard to explain without a whiteboard to draw on or the ability to make illustrative hand gestures because it's very, very mechanical.

Pretty much every chemical you are made of is a protein. Proteins are really, really long molecules which tangle up. But they tangle up in particular ways, based on what you can imagine as springinesses built into them by the order of the constituent atoms in them. So, for instance, hemoglobin is, if you were to stretch it out by either end, one long chain, but when you let go of the ends, it snaps into a shape -- in particular a nanotechnologically sized paperclip. Rather, four paperclips. If oxygen atoms were paper. That's how hemoglobin grasps and carries around oxygen. By clipping on to it, mechanically. Really. Each hemoglobin can clip onto 4 oxygen atoms at a time.

Unless its deformed. Sickle-cell anemia is a disorder of the hemoglobin, where the hemoglobin is made with a single wrong little chunk in exactly the wrong place, to make the whole paperclip fold wrong, such that only two of clips work to grab oxygen.

Proteins are chains of amino acids. We have a whole alphabet of amino acids -- 20 of them. Proteins can be thought of words spelled of amino acids. But they're words which tangle up into useful shapes, because they have springinesses (well, stickinesses) in them.

Our cells, which are the factories of proteins, just make lots and lots of amino acids which float around in a kinda stew, waiting for something to happen. But each amino acid is built with an attachment. The attachment is made of tRNA. tRNA is like DNA, only slightly different. tRNA also has four kinds of base pairs. Each amino acid has hanging off it a little chunk of tRNA that is characteristic of that amino acid. That is, all amino acid A molecules have the same mRNA attached, all the B ones have a different mRNA. Etc. Each mRNA has (IIRC) three base pairs.

So, then: the DNA is unzipped exposing the bases. mRNA makes a copy, then falls away, so there's this mRNA partial copy floating around -- sort of like the photocopy of a single page of a big set of blueprint. tRNA bump into it. Whenever a tRNA's set of three bases match up against the next three bases of the mRNA, they latch on, and the amino acid hanging off the back, bumps up against the amino acid hanging off the back of the previous chunk of tRNA, and bonds to it. By this process a whole long chain of amino acids are made. Then they are broken free from their tRNA, and the sproing into shape and float off.

[continued]

[siderea]

[continued]


So.

What makes hemoglobin is that the hemoglobin-blueprint DNA is copied to a mRNA hemoglobin-blueprint page. tRNA chunks latch on to the blueprint, in the order specifed by the blueprint, and then their amino acids link up into a hemoglobin. A hemoglobin molecule is a big word, spelled in amino acids; the order of the letters is specified in the blue print, encoded in bytes (bases).

Someone with sickle-cell anemia has a typo. They have one letter wrong in the spelling of the word. That's how it's written in their DNA, so every copy perpetuates the error. And because there's the wrong letter there, the hemoglobin doesn't bend where it should.

Someone with the genes for fair skin is not putting out a lot of melanin; someone with the genes for dark skin, is. For whatever reason -- either the melanin itself or some protein precursor which causes cells to produce more melanin is coded for differently at the DNA level. Perhaps melanin is produced in the presence of a certain other protein ("word"). In one person, their DNA spells that word, but in another, their DNA spells a word one letter different, so they don't make that protein which causes melanin production.

How are we doing?

[siderea]

PICTURES!!

P.S. The magic term to google is "protein synthesis" or more precisely "protein biosynthesis" (to differentiate from synthesizing proteins in the lab). Because the way you go from gene to expression is by synthesizing proteins!

[appadil.livejournal.com]

...I had a big long infodump series of posts all typed up, but siderea covered most of it a lot more concisely, and probably more accessibly, than I would have.

The only additions that I want to make to what she's said is to touch on the concept of regulations. Not all genes are turned 'on' and making proteins all the time. There are genes whose specific job it is to make proteins which turn other genes on or off (and sometimes the genes they're flipping turn OTHER regulators on and off!) So, in the skin color example mentioned above, the melanin being made is actually exactly the same, but the genes which control how much of it is made are different.

[appadil.livejournal.com]

Also!

The genetic 'alphabet' has a lot of redundancy in it. There are only 20 amino acids, but there are 64 different three-unit combinations. Two of them don't translate to anything and basically act as 'stop here' signals to let the RNA know where the gene ends and one of them acts as a 'start here' signal, but many of the rest code for the same amino acids as each other. This is important because it means that a lot of copying errors don't actually mess up the protein- for example, "AGU", "AGC" "UUC", "UUA", "UUG", and "UUU" all make the same amino acid, serine.

You're more likely to get a messed up protein by 'stutters' where a nucleic acid gets repeated too many times or two few, or frame-shifts (where it starts reading at the wrong point and basically makes gibberish (so rtofl ik eify ouin serted you rword brea kswrong.)

[velvetchamber.livejournal.com]

Now, as I understand it, your chromosomes themselves just consist of a small number of nucleotides.

No, the chromosomes of plants and animals are most commonly composed of millions base pairs. I do believe that the shortest human chromosome is some 51 million base pairs, and our genome more than 3 billion bases in total. That is a whole lot of information, some of which is vital, some which is flexible, and some that does not matter much at all.

The common wheat on the other hand has around 16 billion bases to their genome, but that's because plants are not so sensitive to polyploidy as we are.

Re: Mysteries de los mysterios!

[conuly]

That's what I thought. More or less. (Okay, when I thought about it at all, which is hardly ever. I *really* disliked bio in high school, and when I go back to school, I'm not looking forward to taking it on the college level AT ALL.)

[conuly]

I've *think* I've got it, but some things may've gone over my head (REALLY disliked high school bio, and endeavored to forget a lot of it). I'll run through it again when I have a spare minute. The girls are playing "having a concert", complete with microphones (where they learn this, I don't know), but who knows how long that'll last?

[caprinus.livejournal.com]

Have you seen this? The definitive interpretation!

http://www.youtube.com/watch?v=u9dhO0iCLww

Re: Mysteries de los mysterios!

[marveen.livejournal.com]

That part did make me blink.

But yes, I was going on vague half-memories of high school, sowwy about that.

[conuly]

Okay. So let me see if I can sum this up, and you can see if I understand the big parts (I think I get the little ones just fine, oddly). (Finally, in my adulthood, I understand the wisdom of asking children to put things "in their own words"!)

So... the nucleotides make amino acids, which make proteins, which make things that I can see in my mind - blood and bones and plants. And this isn't some sort of magic, this is an actual physical process that I could see if I had a strong enough microscope (or were microscopically small, in which case understanding all this would, I'm sure, be quite the least of my worries). And this all makes sense because things are made in certain ways, physically - it's not an obscure code that can only be understood through trial and error and guessing.

If that's the gist of the comments, then I can try working out the details and making sure I really do understand those. If not, I totally misunderstood anyway.

[conuly]

Thank you.

[siderea]

I think so, but I'm not sure I understand the assumption in "it's not an obscure code that can only be understood through trial and error and guessing".

Certainly, that's how the correspondences between specific genes and specific amino acids was worked out. I don't think we have microscopes fine enough to actually watch molecular-scale phenomena (yet! :) so whole large chunks have been deduced. But the process is all very mechanical and pretty well understood -- it's all very well confirmed.

One of the things which was hard for me to wrap my mind around when I was learning this, is these processes -- all biochemical processes, AFAIK -- function by the equivalent of putting a bunch of magnets in a big sack with various kinds of bits of metal, and shaking the sack, such that all the bits of iron cling to the magnets, but none of the copper or aluminum does. Except that in biology, it's not as simple as "magnetic" and "not-magnetic", there's all sorts of different compounds which bind with some but not other compounds.

A lot of -- all? -- biology proceeds on the "some stuff is sticky to other stuff, so you just have to put the right stuffs in a cell together, and it will naturally just stick to one another when they bump". When a DNA double helix is unzipped, each of those bases is sticky -- its sticky bond with its mate has just been broken, so the sticky end is waving around, waiting to stick to something. Stray bits of RNA are correspondingly sticky, so when they bump, they stick. If you have half a DNA strand and it's in a jar with lots of RNA, some of the RNA sticks to the DNA, and it sticks to one another even better.

So more properly, ordered strands of nucleotides organize amino acids into proteins. Amino acids make up proteins.

(Where do amino acids come from? Two places: some an organism can synthesize from other compounds, others the organism has to eat. The latter are "essential amino acids". From wikipedia:

Nine amino acids are generally regarded as essential for humans: phenylalanine, valine, threonine, tryptophan, isoleucine, methionine, histidine, leucine, and lysine.

That is, we have to eat foods with those chemicals (amino acids) in them, digest them to get at the amino acids, and then our RNA can use those liberated amino acids from our food to make into proteins (as ordered by our DNA-blueprint) that we're made up of. (Thus we are what we eat! This is how our food becomes our blood and bone and muscle and skin and all!) Other amino acids we can make out of other things (which largely we also eat. :))

[siderea]

The canonical work on the topic! My goodness, we saw that in high school. A classic.

[conuly]

Got it. Well, if we could see small enough, we would no longer have to use trial and error, then :) I mean to say, it's not totally incomprehensible.

[siderea]

Right! We've got the process pretty well down, and now are busily figuring out which parts of the blueprint make which chunks of humans, and what all the variations and their effects are.

Mysteries de los mysterios!

[marveen.livejournal.com]

I probably butchered the spanish there, but it's my understanding that scientists are working doggedly on figuring out exactly HOW it is that a sequence of G-T-A-C etc. can convey the information that codes to "red hair/freckles/green eyes with brown specks/sparse eyebrows/pointed chin".

(I'll also point out that plants have RNA, we have DNA. One of those small differences, like polarity, that turns out to be vital.)

I suppose the DNA mystery is much like the way the computer codes its screen colors (yours show up as a banana yellow, burnt orange trim, with grey links) using only the on/off switches.

[hopefulnebula]

One of my uncles says the same thing about high school science. It makes a lot of sense.

Re: Mysteries de los mysterios!

[appadil.livejournal.com]

(I'll also point out that plants have RNA, we have DNA. One of those small differences, like polarity, that turns out to be vital.)

I'm sorry, but that's completely inaccurate. Plants (and indeed, all known living things if you don't think of viruses as properly 'alive') use DNA for their genetic code. RNA is used to help translate RNA into protein, and is also used as the genetic code by most (but not all) viruses.

Re: Mysteries de los mysterios!

[appadil.livejournal.com]

...damn. That should be "translate DNA into protein."

[siderea]

I know this one!

I'm going to oversimplify like mad, and then, if you want to inquire further, I may back up and desimplify as necessary.

Now, as I understand it, your chromosomes themselves just consist of a small number of nucleotides. So what makes a specific combination of nucleotides say "make this pea green" or "this one's gonna be a yellow pea" or even (in the case of extreme manipulation or random mutation) "purple all the way"?

First, let's ask what makes the greenness and yellowness in peas. Well, we know that. The greenness is chlorophyl, a chemical. The yellowness is, er, the natural color of the cell walls I think. Whatever.

Think also for a moment about skin color. What makes skin color? Melanin. A chemical.

What the specific combination of nucleotides control is the production of chemicals.

So now the question is "how do you get from a combination of nucleotides to different chemicals in different amounts?"

THe answer to that is "RNA Transcription" and it's way cool and very hard to explain without a whiteboard to draw on or the ability to make illustrative hand gestures because it's very, very mechanical.

Pretty much every chemical you are made of is a protein. Proteins are really, really long molecules which tangle up. But they tangle up in particular ways, based on what you can imagine as springinesses built into them by the order of the constituent atoms in them. So, for instance, hemoglobin is, if you were to stretch it out by either end, one long chain, but when you let go of the ends, it snaps into a shape -- in particular a nanotechnologically sized paperclip. Rather, four paperclips. If oxygen atoms were paper. That's how hemoglobin grasps and carries around oxygen. By clipping on to it, mechanically. Really. Each hemoglobin can clip onto 4 oxygen atoms at a time.

Unless its deformed. Sickle-cell anemia is a disorder of the hemoglobin, where the hemoglobin is made with a single wrong little chunk in exactly the wrong place, to make the whole paperclip fold wrong, such that only two of clips work to grab oxygen.

Proteins are chains of amino acids. We have a whole alphabet of amino acids -- 20 of them. Proteins can be thought of words spelled of amino acids. But they're words which tangle up into useful shapes, because they have springinesses (well, stickinesses) in them.

Our cells, which are the factories of proteins, just make lots and lots of amino acids which float around in a kinda stew, waiting for something to happen. But each amino acid is built with an attachment. The attachment is made of tRNA. tRNA is like DNA, only slightly different. tRNA also has four kinds of base pairs. Each amino acid has hanging off it a little chunk of tRNA that is characteristic of that amino acid. That is, all amino acid A molecules have the same mRNA attached, all the B ones have a different mRNA. Etc. Each mRNA has (IIRC) three base pairs.

So, then: the DNA is unzipped exposing the bases. mRNA makes a copy, then falls away, so there's this mRNA partial copy floating around -- sort of like the photocopy of a single page of a big set of blueprint. tRNA bump into it. Whenever a tRNA's set of three bases match up against the next three bases of the mRNA, they latch on, and the amino acid hanging off the back, bumps up against the amino acid hanging off the back of the previous chunk of tRNA, and bonds to it. By this process a whole long chain of amino acids are made. Then they are broken free from their tRNA, and the sproing into shape and float off.

[continued]

[siderea]

[continued]


So.

What makes hemoglobin is that the hemoglobin-blueprint DNA is copied to a mRNA hemoglobin-blueprint page. tRNA chunks latch on to the blueprint, in the order specifed by the blueprint, and then their amino acids link up into a hemoglobin. A hemoglobin molecule is a big word, spelled in amino acids; the order of the letters is specified in the blue print, encoded in bytes (bases).

Someone with sickle-cell anemia has a typo. They have one letter wrong in the spelling of the word. That's how it's written in their DNA, so every copy perpetuates the error. And because there's the wrong letter there, the hemoglobin doesn't bend where it should.

Someone with the genes for fair skin is not putting out a lot of melanin; someone with the genes for dark skin, is. For whatever reason -- either the melanin itself or some protein precursor which causes cells to produce more melanin is coded for differently at the DNA level. Perhaps melanin is produced in the presence of a certain other protein ("word"). In one person, their DNA spells that word, but in another, their DNA spells a word one letter different, so they don't make that protein which causes melanin production.

How are we doing?

[siderea]

PICTURES!!

P.S. The magic term to google is "protein synthesis" or more precisely "protein biosynthesis" (to differentiate from synthesizing proteins in the lab). Because the way you go from gene to expression is by synthesizing proteins!

[appadil.livejournal.com]

...I had a big long infodump series of posts all typed up, but siderea covered most of it a lot more concisely, and probably more accessibly, than I would have.

The only additions that I want to make to what she's said is to touch on the concept of regulations. Not all genes are turned 'on' and making proteins all the time. There are genes whose specific job it is to make proteins which turn other genes on or off (and sometimes the genes they're flipping turn OTHER regulators on and off!) So, in the skin color example mentioned above, the melanin being made is actually exactly the same, but the genes which control how much of it is made are different.

[appadil.livejournal.com]

Also!

The genetic 'alphabet' has a lot of redundancy in it. There are only 20 amino acids, but there are 64 different three-unit combinations. Two of them don't translate to anything and basically act as 'stop here' signals to let the RNA know where the gene ends and one of them acts as a 'start here' signal, but many of the rest code for the same amino acids as each other. This is important because it means that a lot of copying errors don't actually mess up the protein- for example, "AGU", "AGC" "UUC", "UUA", "UUG", and "UUU" all make the same amino acid, serine.

You're more likely to get a messed up protein by 'stutters' where a nucleic acid gets repeated too many times or two few, or frame-shifts (where it starts reading at the wrong point and basically makes gibberish (so rtofl ik eify ouin serted you rword brea kswrong.)

[velvetchamber.livejournal.com]

Now, as I understand it, your chromosomes themselves just consist of a small number of nucleotides.

No, the chromosomes of plants and animals are most commonly composed of millions base pairs. I do believe that the shortest human chromosome is some 51 million base pairs, and our genome more than 3 billion bases in total. That is a whole lot of information, some of which is vital, some which is flexible, and some that does not matter much at all.

The common wheat on the other hand has around 16 billion bases to their genome, but that's because plants are not so sensitive to polyploidy as we are.

Re: Mysteries de los mysterios!

[conuly]

That's what I thought. More or less. (Okay, when I thought about it at all, which is hardly ever. I *really* disliked bio in high school, and when I go back to school, I'm not looking forward to taking it on the college level AT ALL.)

[conuly]

I've *think* I've got it, but some things may've gone over my head (REALLY disliked high school bio, and endeavored to forget a lot of it). I'll run through it again when I have a spare minute. The girls are playing "having a concert", complete with microphones (where they learn this, I don't know), but who knows how long that'll last?

[caprinus.livejournal.com]

Have you seen this? The definitive interpretation!

http://www.youtube.com/watch?v=u9dhO0iCLww

Re: Mysteries de los mysterios!

[marveen.livejournal.com]

That part did make me blink.

But yes, I was going on vague half-memories of high school, sowwy about that.

[conuly]

Okay. So let me see if I can sum this up, and you can see if I understand the big parts (I think I get the little ones just fine, oddly). (Finally, in my adulthood, I understand the wisdom of asking children to put things "in their own words"!)

So... the nucleotides make amino acids, which make proteins, which make things that I can see in my mind - blood and bones and plants. And this isn't some sort of magic, this is an actual physical process that I could see if I had a strong enough microscope (or were microscopically small, in which case understanding all this would, I'm sure, be quite the least of my worries). And this all makes sense because things are made in certain ways, physically - it's not an obscure code that can only be understood through trial and error and guessing.

If that's the gist of the comments, then I can try working out the details and making sure I really do understand those. If not, I totally misunderstood anyway.

[conuly]

Thank you.

[siderea]

I think so, but I'm not sure I understand the assumption in "it's not an obscure code that can only be understood through trial and error and guessing".

Certainly, that's how the correspondences between specific genes and specific amino acids was worked out. I don't think we have microscopes fine enough to actually watch molecular-scale phenomena (yet! :) so whole large chunks have been deduced. But the process is all very mechanical and pretty well understood -- it's all very well confirmed.

One of the things which was hard for me to wrap my mind around when I was learning this, is these processes -- all biochemical processes, AFAIK -- function by the equivalent of putting a bunch of magnets in a big sack with various kinds of bits of metal, and shaking the sack, such that all the bits of iron cling to the magnets, but none of the copper or aluminum does. Except that in biology, it's not as simple as "magnetic" and "not-magnetic", there's all sorts of different compounds which bind with some but not other compounds.

A lot of -- all? -- biology proceeds on the "some stuff is sticky to other stuff, so you just have to put the right stuffs in a cell together, and it will naturally just stick to one another when they bump". When a DNA double helix is unzipped, each of those bases is sticky -- its sticky bond with its mate has just been broken, so the sticky end is waving around, waiting to stick to something. Stray bits of RNA are correspondingly sticky, so when they bump, they stick. If you have half a DNA strand and it's in a jar with lots of RNA, some of the RNA sticks to the DNA, and it sticks to one another even better.

So more properly, ordered strands of nucleotides organize amino acids into proteins. Amino acids make up proteins.

(Where do amino acids come from? Two places: some an organism can synthesize from other compounds, others the organism has to eat. The latter are "essential amino acids". From wikipedia:

Nine amino acids are generally regarded as essential for humans: phenylalanine, valine, threonine, tryptophan, isoleucine, methionine, histidine, leucine, and lysine.

That is, we have to eat foods with those chemicals (amino acids) in them, digest them to get at the amino acids, and then our RNA can use those liberated amino acids from our food to make into proteins (as ordered by our DNA-blueprint) that we're made up of. (Thus we are what we eat! This is how our food becomes our blood and bone and muscle and skin and all!) Other amino acids we can make out of other things (which largely we also eat. :))

[siderea]

The canonical work on the topic! My goodness, we saw that in high school. A classic.

[conuly]

Got it. Well, if we could see small enough, we would no longer have to use trial and error, then :) I mean to say, it's not totally incomprehensible.

[siderea]

Right! We've got the process pretty well down, and now are busily figuring out which parts of the blueprint make which chunks of humans, and what all the variations and their effects are.