LUCA is LOCO!

[Wally]

Okay, I'm back from work.

While I was driving I realized that we may have had a "communication failure" (if we did I'll take responsibility for it).
Let me explain briefly with an analogy: If I write a message containing 1,200 alphanumeric characters and I "displace/substitute" one of those characters then the message will very likely remain readable and comprehensible - i.e., function is retained. And that can be done for just about any of the characters. Some characters, however, would not tolerate any change. End of example.

With that analogy, do you see what the miscommunication may have been? I was thinking of simultaneous (1050 out of 1100) changes whereas you were thinking/saying individual (1050 out of 1100) changes.

I will be happy to take the blame for that miscommunication if that was indeed what happened. If, however, you actually meant that 1050 out of 1100 simultaneous changes could occur without loss of function, then the game is still on.

I doubt that that's the case so, since I've taken the responsibility for the miscommunication, I'm calling this a "draw".

But that's not the end of it. I also did other thinking on this (I drove for over an hour):

(1) Allowing for even a (relatively) few simultaneous variations that retain function, the size of the set of possible sequences is still astronomical. Combine that with...

(2) ... the ratio of the sequences that produce the required structure (2ndary, tertiary) versus the total set of possible sequences is still infinitesimal.

Yes, the numbers are "less" (probabilities are "higher"). So go ahead, feel free to subtract 300, 400 or 600 orders of magnitude due to allowable variations that retain function (I'm being generous). That will still leave hundreds of orders of magnitude in the set of possibilities. In other words, the challenge that I posed in the OP remains intact.

Thanks.

Jorge

And you have the temerity to claim the Clintons are dishonest!

[Jorge]

Keep driving Clucky. You're still pushing the same wrong "sequences had to fall together all at once" nonsense instead of the actual known evolutionary process of slow change from a working precursor. For each generation evolution didn't have to explore your ginormous search space. It only had to explore the space one mutational step away from its currently functioning arrangement.

Your "challenge" is based on nothing more than your ignorance and misunderstanding.

............... You give new meaning to the word STUPID.

Jorge

[Jorge]

And you have the temerity to claim the Clintons are dishonest!

Just for my amusement, this I got'ta hear .................

Tell me - Oh Swami Wally - how is any of the referenced post "dishonest"?

Ummm ... use only coherent English, please.

Jorge

[HMS_Beagle]

You give new meaning to the word STUPID.

But Clucky, you're the one putting your stupidity on display by making the same dumb claim after being corrected half a dozen times.

[TheLurch]

BTW - I am interested in whatever your extended search might turn up if you are interested enough yourself to do the extra work. Don't do it just on may account though :)

I'll get back to the larger argument in a bit, but i did come up with the following:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1451187/

Which seems to be relevant to this issue. Money quote from the abstract:
"Moreover, a likelihood analysis of mutation diversity predicts that, on average, a deleterious mutation can be compensated by about nine different intragenic compensatory mutations. "

Gives some sense about the tolerance for amino acid changes in most proteins.

[oxmixmudd]

Adults are talking here, O-Mudd.
Go back to your sandbox and remain silent, okay!
Either that or no ice cream for you tonight.

Jorge

Another post by Jorge with palpable intellectual power and honesty ...

[Jorge]

I'll get back to the larger argument in a bit, but i did come up with the following:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1451187/

Which seems to be relevant to this issue. Money quote from the abstract:
"Moreover, a likelihood analysis of mutation diversity predicts that, on average, a deleterious mutation can be compensated by about nine different intragenic compensatory mutations. "

Gives some sense about the tolerance for amino acid changes in most proteins.

A reasonable point for you to ponder: It is relatively easy to make "changes" to a 25-bedroom, 20-bathroom mansion. Furthermore, that mansion can "tolerate" those changes, remaining functional all throughout.

For you the not-easy-at-all question is, how did that mansion originally get there?

Do you 'get' my analogy or do I need to spell it out?

Jorge

[Jorge]

Another post by Jorge with palpable intellectual power and honesty ...

You just don't know when to shut up, do you.

You must've had many "no ice cream for you tonight" days as a kid!

Jorge

[Jorge]

I'll get back to the larger argument in a bit, but i did come up with the following:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1451187/

Which seems to be relevant to this issue. Money quote from the abstract:
"Moreover, a likelihood analysis of mutation diversity predicts that, on average, a deleterious mutation can be compensated by about nine different intragenic compensatory mutations. "

Gives some sense about the tolerance for amino acid changes in most proteins.

Ummm ... I had stated that the 'challenge' in the OP remains valid. Are you conceding that point?

Jorge

[TheLurch]

Ummm ... I had stated that the 'challenge' in the OP remains valid. Are you conceding that point?

Jorge

What part of "I'll get back to the larger argument in a bit" wasn't clear?

[Jorge]

What part of "I'll get back to the larger argument in a bit" wasn't clear?

Given that that post was addressed to oxmixmudd, it wasn't clear to me at all.

Now say, "Oops!" and carry on.


Oh and, while I have your attention, don't forget this:

A reasonable point for you to ponder: It is relatively easy to make "changes" to a 25-bedroom, 20-bathroom mansion. Furthermore, that mansion can "tolerate" those changes, remaining functional all throughout.

For you the not-easy-at-all question is, how did that mansion originally get there?

Jorge

[oxmixmudd]

You just don't know when to shut up, do you.

You must've had many "no ice cream for you tonight" days as a kid!

Jorge

And you apparently never figured out it is wrong to lie ...

You know, regardless of what you think of me, you have an obligation to God, not to me, to fix the lies in your paper on asteroid impacts. At this point, all I am is God's provision for the conscience you don't own.

But speaking of that, you see how I'm hounding you over this issue, and I just won't let it go?

THAT is what a conscience is. That is what it does. Most people would not need me to hound them over this, because they would have a conscience, and their conscience would do exactly what I'm doing all on its own.

But since you don't have one, you probably are not aware of just how annoying and how relentless a conscience can be.

Now you know.


Jim

[Jorge]

And you apparently never figured out it is wrong to lie ...

You know, regardless of what you think of me, you have an obligation to God, not to me, to fix the lies in your paper on asteroid impacts. At this point, all I am is God's provision for the conscience you don't own.

But speaking of that, you see how I'm hounding you over this issue, and I just won't let it go?

THAT is what a conscience is. That is what it does. Most people would not need me to hound them over this, because they would have a conscience, and their conscience would do exactly what I'm doing all on its own.

But since you don't have one, you probably are not aware of just how annoying and how relentless a conscience can be.

Now you know.

Stop it ... I can't stand it!


Jorge

[HMS_Beagle]

Stop it ... I can't stand it!

Wow Clucky, you're really making a major league ass of yourself today, even more so than normal.

Do continue.

[TheLurch]

I was thinking of simultaneous (1050 out of 1100) changes whereas you were thinking/saying individual (1050 out of 1100) changes.

Ok, this would explain the back and forth. So, we'll write that off for now, and say that it appears that we both agree that you can change a very, very large fraction of the amino acids of most proteins individually without affecting its function, but you can't change them simultaneously and expect the same result.

I'll just return to my original post for a moment, and point out this seems to accept my original point: nobody knows what the numerator in the probability is, but it's certainly not 1. So, as far as i can tell, we're all good on the point that got me involved here.


You've now also clarified your larger point:

(1) Allowing for even a (relatively) few simultaneous variations that retain function, the size of the set of possible sequences is still astronomical. Combine that with...

(2) ... the ratio of the sequences that produce the required structure (2ndary, tertiary) versus the total set of possible sequences is still infinitesimal.

Yes, the numbers are "less" (probabilities are "higher"). So go ahead, feel free to subtract 300, 400 or 600 orders of magnitude due to allowable variations that retain function (I'm being generous). That will still leave hundreds of orders of magnitude in the set of possibilities. In other words, the challenge that I posed in the OP remains intact.

I think everyone here would agree that, if you simply plotted the fitness landscape for an 1,100 amino acid long protein, and compared that to the area (or areas, we don't know) within it that contains a functional reverse gyrase, the ratio of that area to the landscape would be incredibly small, even though the island(s) of related functional sequences might be extremely large.

But, as numerous others have been pointing out, nobody here is suggesting that a functional 1,100 amino acid long protein simply poofed into existence. In other words, there's no indication that the entire fitness landscape ever had to be searched in the first place. So, yes, it's an infinitesimal probability; but everyone here agrees that it's the probability of an event that never occurred (though we clearly think that for different reasons).


Now, the argument that is being put forward, notably by Roy (though i elaborated a bit), is that the protein has a very modular design, with many of the modules having useful functions in contexts other than reverse gyrase. And each of these modules is far, far smaller than the full reverse gyrase.

The separate evolution of these modules doesn't entirely eliminate the issue you argue (small functional sequence islands in an ocean of search space), but it changes the nature of the argument considerably, i'd think. It's not an argument i've pursued up to this point personally, but i'm willing to engage in it.


Anyone disagree that this is a fair summary of things so far?