##( mork calling hometown... come in hometown! )##

[galathaea]

I just saw your question about block substitution matrices over in the vc++ forum and wanted to make a few comments. However, we should stick to a more appropriate forum. I'd PM you, but its very difficult to use PMs because I easily hit the ceiling and have to break responses into several separates (which begs the question of why there are limits in the first place since I will take up just as much if not more database space because I won't be confined that easily -- same goes for forum posts but at least I don't have to break things up as often).

First I should stress that those kinds of calculations are not really a focus of mine. I've tossed together a few programs before to calculate phylogenetic information from sequences to help me study, but those involved more simplified models than the programs the professionals use regularly. But I'll try to explain what I can.

Laboratories everywhere these days are cranking out gene sequences. There is a whole industry of rather poorly paid lab techs who chop up genomes, gel separate them, run PCRs, and then do various spectral or antibody tests to identify the various fragments. What this results in is a huge collection of DNA sequence information from all sorts of bacteria, plants, fungi, animals, etc. being passed around the scientific and industrial communities. ACCTGTCGATTACA...

One of the useful pieces of information that can be formed from this information is the evolutionary relationships between the various species. The basic theory is that DNA sequences which differ by a lot indicate species which diverged evolutionarily furthur back in history than sequences which are more closely similar.

However, one needs to come up with a good measure for the differences between sequences. One of the simpler possibilities is to just use an extended Hamming distance, where you just count the number of different letters per position in a sequence. However, this is not very useful because one common evolutionary mutation is an insertion event, which will put a new nucleotide or series of nucleotides into a sequence somewhere in the middle of a gene, tossing off all subsequent matches and indicating a large distance between the sequences even though only one evolutionary event occured.

So instead, the similarities are often weighted and a pattern matching algorithm is applied to measure the distances, and often the algorithms are applied to a full codon (3 nucleotides - which collectively code for one amino acid in the gene's protein product). The reason there needs to be a weighting is because another common evolutionary event is substitution, and it has been found that substitutions are more common between amino acids that share similar biochemistries. So experiments have been done, and various substitution theories have been developed. Most often these are represented in scoring matrices, such as the various BLOSUMs. Effectively, each type of scoring matrix describes a particular evolutionary model being applied.

It looks like the question is asking to just basically look up in the matrix the corresponding substitution values between various amino acids with similar properties (for example, V is valine), in order to illustrate to the student that they will have proportionately more likelihood for substitution. I don't have a copy of the BLOSUM50 matrix around, so I couldn't help out much with walking through the problem, but I'm sure its out there on the internet, maybe even on the site your question comes from. But its basically looking things up in a matrix, and not too exciting.

However, as I mention above, this isn't really the field I am most interested in. Particularly recently, I have been much more focused on simulations surrounding the origins of life.

[hometown]

If I use hometown to post like that, hometown willnot be able to meet you and many friends here again...
Mr Jones will ban hometown....It s the first time snoopy does that, so perhaps she will recieve a warning or so, but hometown is still safe.

Okay, forget about that, I also will not do that again...

Thanks galathaea very much for your answer....That s really great and kind of you to explain that problem for me...But honestly, I dont understand many technical terms you used...I am not in biology field...True.

Uhm, I am on the wrong way again...
But could you tell me what you mean by "simulation surrounding origins of life" ? Can you give me an example ? As I said in PM, I couldnot imagine what simulation that is ?

Thanks alot,

Fiona

[galathaea]

Hehe, you know if galathaea talked like hometown or snoop, they'd all think we were in serious trouble of falling into one of those interdimensional personality vortices that always swallows the crazy people. Vrais!

So, we are reaching this really exciting time with technology. There is one question we may be very close to answering that has always been one of those obsessions of mine. Which is:

What is it about the universe that makes life just spontaneously arise?

I mean:

How do the laws of nature describe ways in which life can form?

Its one of those really popular questions that a lot of people have worked on for hundreds of years. Its a topic is this still somewhat taboo in certain company because it is still a topic that various religions claim answers for (my 9th grade biology teacher refused to ever even touch the problem because he was also a devout fundamentalist christian). Its so mysterious that it is a source of much fiction, from Clarke's 2001 series to Star Trek.

Its the genesis point.

Most people don't have a problem understanding why life continues to exist, because that seems to be the nature of life. In fact, that is pretty much the most basic way it is defined these days, as the persistence of an information structure through time. What is difficult is that step from the moment before the stable information structure to the moment after. Its a sudden change. Either information persists or it dies out. Its a phase transition, very similar to the change from liquid to solid.

Finding out what happened during that change, though, requires more refinement as to which type of information persistence is being studied, and the one that seems most relevant to the structure we call life on Earth has to do with chemical reactions. We see life in the metabolism here, the network of chemical reactions that is structured in time and space to be able to provide a frequent enough food source to maintain the metabolism.

And its been figured out over the past hundred years or so what this implies. In particular, this is saying that there is some stage in complexity of a chemical reaction where it is possible to begin autocatalysis which maintains structure beyond the food set. A loop must form. AKA hypercycles. That is the phase change I have spent most effort studying.

Chemical reactions occur because there is a free energy cascade possible between products and reactants. In order to maintain a reaction net, the local thermodynamics of the system has to have been pushed away from equilibrium.

And it seems fairly clear that life on Earth seem to arise in particular from the reaction coordinates made available by six or seven primary elements: hydrogen, carbon, nitrogen, oxygen, phosphorous, and sulfur, perhaps with an interesting assist from iron. These elements are quite common in third generation solar systems (normal the sequence is first generation suns have mostly hydrogen / helium gaseous systems, second generation are carbonaceous stony dust filled with ices, and third generations introduce the irons and heavier rocky minerals).

Carbon forms the skeleton of the reaction grammar. Its unique molecular properties make it able to form adaptable (soft-squishy) structures which can link together in a lot of useful and relatively stable ways. Hydrogen, nitrogen, and oxygen seem to work together to form points of acid / base variation along the carbon skeleton.

Acids and bases are defined in two different ways which focus on two rather different pathways of energy cascade: either proton / hydroxide transfer (or general functional group) or electron transfer.

On the early earth (but after the best part of the hadean era which spanned between approx. 4.6 to 3.9 billion years ago - at least after the big planetary collision that caused the moon and probably once the impact events had subsided enough to no longer be completely sterilising), there were already basic geochemical cycles that had formed around various energy sources. Carbonate minerals took up a good deal of the carbons and oxygens, hydrogen was delivered in icy impacts (since much of the early oceans were initially vaporised by early impacts), and nitrogen was a common atmospheric component which also dissolved in the oceans.

Phosphates provide for great temporary energy transfer between carbon skeletons through the functional group transfer mechanism, because compared to hydrogen or hydroxide, they can be made to interact weakly outside the carbon skeleton reaction network (so they can be energy messengers, whereas the hydrogen / oxygen / nitrogen system provides more global environment to alter reaction equilibria). In fact, they are a great abstraction of the energy transfer mechanism along this pathway. Unfortunately, this atom's properties do not provide natural (inorganic / prebiotic / or whatever you wish to call it) energy source.

Iron sulfide (pyrite, fools gold) is a common mineral found in the Earth's core and mantle. It extrudes to the crust around volcanic tubes. And it seems to play a key role in the final steps necessary for life to begin on Earth, as it provides a source of free energy around which cascades can form. It is a reducing agent which provides energy through the reaction

FeS + H2S -> FeS2 + 2e- + 2H+

This reaction ties everything together, because it provides an electron transport connection to an energy source that couple directly to functional transport mechanisms through thioester mechanisms such as

CO2 + FeS + 2H2S -> CH3-SH + FeS2
CH3-SH + CO -> CH3-CO-SH (and the S can be immediately replaced by free oxygen to give ethanol). That's all you need to start building a carbon skeleton and is the basic pattern found in reductive acetyl-CoA pathway that lies at the heart of the citric acid cycle that forms the center of all existing metabolisms. In fact, when you look at the enzymes which catalyse and otherwise make more efficient this central metabolic pathway, you find that they have Fe/S cores as active sites. Additionally, many of the most anciently divergent bacteria and archaebacters (eg. Sulfulobus, desulfurococcus) have metabolisms still tightly coupled to reductive sulfur sources, and these very likely formed prior to methanogens and photosynths, and definitely prior to respirers (no oxygen back then).

So there is this foundation on which biogenesis is becoming understood. However, there is still no direct, full linkage between these early autocatalytic sets and the cellular forms of modern life. Although there are certainly milestones where big guesstimates can be made (such as the fact that such an early system, particularly in and around a hydrothermal event, could present clay and iron/sulfide surfaces which posses the proper polarity properties for surface binding of lipid-like chains, and these lipid surfaces can grow and bud naturally, providing an early compartmentalisation source), it has been very difficult in the past to wade through the huge number of chemical reactions which could occur to suggest any actual possible pathways to finish the link from early chemistry to modern life.

This is where ab initio molecular orbital theory comes in. It has recently become possible to establish computer simulations that can perform basis set expansions of the basic quantum mechanical equations of atomic structure to an accuracy where reaction characteristics (rate constants, activation energies, etc.) can be directly computed. In fact, this is one of the way pharmaceutical companies model binding studies to receptors. The GAUSSIAN software package is quite heavily used in research these days, and other packages have appeared for specialised communities. And with the regular increase in computer speeds, the simulations sets are growing in scope. Very soon, we will be able to run full reaction space searches surrounding these major chemicals and others as well and establish actual reaction histories that potentially detail the possible origins of life.

That is the thing that interests me most. And although I would like to get back to school and contribute to this fascinating study that is occuring, I will be content to watch the pieces be put together by others. To me, it is one of the most beautiful places in science.

One interesting final note. To a great extent, the study of biogenesis is a study of graph dynamics, as that is the basic dynamical structure of a metabolism. I've always been quite amused at the fact that modeling the brain with neural nets is also a graph dynamics, with exact mathematical correspondence between autocatalysis and the formation of attractor cycles. And attractor cycles are currently accepted in cognitive science as the neural representative of concepts in the abstraction process. In other words, the study of biogenesis is the same information structural study as the origin of concepts and the abstracting mind.

[Mick]

Originally posted by galathaea

Laboratories everywhere these days are cranking out gene sequences.

Mostly in Maryland thank you very little

[Andy Tacker]

Originally posted by galathaea

Are you in R&D Hon'?

[hometown]

Originally posted by Galathaea
Hehe, you know if galathaea talked like hometown or snoop, they'd all think we were in serious trouble of falling into one of those interdimensional personality vortices that always swallows the crazy people. Vrais!

No, dont do that, I mean we have to have something...ours only () (just joked)

Thanks Galathaea very much,
You did give me a really interesting introduction on the origins of life on Earth...I find it interesting.really...
Although I couldnot 100% grasp the whole thing you said, I think I will try my best to "chase" it as fast as possible. I already ordered some of the books as you advised. Two weeks later they will come...

[galathaea]

Originally posted by hometown
Although I couldnot 100% grasp the whole thing you said, I think I will try my best to "chase" it as fast as possible. I already ordered some of the books as you advised. Two weeks later they will come...

Its not important to get everything. The idea is to just "hear the music", start getting a feel for how things are related. I never understand everything when I first look at a new subject. After first reading a textbook, I'm lucky if I can do maybe 10% of the problems. So instead, I just look through things and try to recognise the actors, see which objects are being played around with, see how those objects move around and change.

Here, the little critters being studied are the atoms and molecules. They change by reacting. And each of them affect how others change by something called catalysis.

That's all you need to know at first. The specifics come a little later.

Now if your interested in the beginnings of life, you find out that these reactions can have a very interesting property called autocatalysis, where when you put enough of these things together suddenly a huge web of molecules can keep itself from decaying away as long as its got an energy source.

And thats interesting in and of itself. Ilya Prigogine (who sadly died recently) spent years studying just that. There are all sorts of interesting things that go on inside such networks.

But lets say you're still interested in life on Earth. Now that you have a basic understanding of autocatalysis, you need to understand where the energy came from to make life. Certain critters (iron sulfide, thioesters) actually connect up the electron transport and member transport mechanisms and form the center of the metabolism. They are certainly an important place to look.

One can go all sorts of directions. One might be interested in studying solar system formation and nucleogenesis if one wants to tie things with the past. One might study the various RNA-world vs proteins-first debates to see how later life mechanisms formed, even following them into bacteria and on to the oxygen crisis and the formation of eukaryotes. One could be interested in the evolution of biological forms and might look into the works of D'Arcy Wentworth Thompson or Rene Thom.

But don't worry about knowing everything along the way. You'll get comfortable with the things you are interested in. Follow your interests. You have a lot of eagerness, which is beautiful. Just don't get frustrated along the way, because getting comfortable with things takes time and coming back at things from different angles. Eventually you get the right epiphanies and things click.

I'm glad to hear you are picking up some books, because they are really easy to look at and often offer a lot more information than is currently available online. But as I've also mentioned, check out some of the stuff online. One of the saddest things to me are the books that don't get looked at often (or even all the way through), and this usually happens to me when I don't pick the right books to buy. So usually I like to get a feel for which books the online community interested in the subject is excited about. Its all about picking the good sources that pick the good sources that... Again, funnily like neurons. So, to me, buying books is a big decision, and I just wanted to stress that you should make sure a particular book has what you are interested in inside it. I'm sure that is the case here because I know what you are probably refering to, but I just wanted to make it clear that not all books I reference would be my first choice to suggest someone buy.

Live happily. Persue the things that make you happy. The days are gonna start getting longer here very shortly. Its a new year. Don't let anyone ever tell you you can't do something.

Originally posted by Andy Tacker
Are you in R&D Hon'?

No.
I just smoke weed.

[hometown]

Thanks Galathaea a lot,

Fiona

[vu_]

First Fiona, I didn't know where to begin to tell you, but I must say that I also find myself confused about some of your posts. But it is ok, lets forget about it.....
Short message for you, if you come back read this: There is always mess that people make up, you shouldn't try to clean them up. Because their making mess is just to put food on their table. It's hard to make a living in reality. You're differerent and you haven't spent day and night to be severely reprimanded by boss so that you can put into your pocket some dollars.
Said many times, but one more time and one more time etc, mightnot ever seem enough...Don't worry, I am not offensive, Because we are human, short of memory...so, I think you might have forgotten !!!


Second, I post right in this thread, so I am sure my evolutionary professor already undestand the main purpose of what I really would like to tell...

I call you professor, I hope you already understand how exactly I am thinking about you...We used to give each other some nice words, right ? But there is one thing I would like you to know for sure that Fiona and I have never had any intentions to be impolite to you...Please trust me on that ! And now my coming here to post in your thread is only to stress that one more time...

I don't come to post much because I don't have any problems, all of the solutions to my problems are all around the net, I come here to read and know quite well how everything is going on.

As far as I know, Humanity had evolved three distincly different brain circuits for mating and reproduction. One circuit is for the sex drive, the second one is for romantic love and the last one is attachment, that sense of calm that you can feel with a long-term partner. All of these have close relations to each other.

Scientifically, women love words, and Words are also women's tool. When a woman hears some words from the one she loves, she would have a feeling of the romantic passion, which is a very important point and that also tells us that some parts of the brain that have relations to such feelings are being in an active state. It is not only for love words but for any other stimuli like getting mad, getting excited etc...you can still have the same conclusion.

However, everyone I think should know that itis not as much the words as it is all the activity that goes with the words, and since women love words, this can become a real target for sex cybers that hiding everywhere on the net with different names, like mutiagents in a unique system evironment...it is different from people to people, but the main purpose is to satisfied themselves, they don't have to pay for anything but still able to reach the climax.

As far as I have observed, their words become more, and their actions get more and more active, and you know, they becomes more than or over a normal level whenever those people have any clues about any possibilities to suck their targets in, even though such clues are just a few, some. But what is exactly in their words ? I think it also changes much between people. When you hear "I love you" without any inflection, in most of situations, it will be hard for you to have any romantic passion than the one with some kind of inflection, right?.
But how can people use inflections in such three boring words? I don't know, but I can say those words are boring and the fact is that there are not many couples who will give each other such words, This is why I think another way of communication comes into existence, it is non-verbal. I didn't mean people with so many words are liars, but their words are easily recognized as true or false when you turn yourself into them, under what situations they would say this, under what circumstances they would say that and many many more.....
I don't focus on any pictures before me, because the transition from cut-to-fit craftmanship to the automated mass-production of goods from interchangeable parts already took about 200 year, it went from the interchangeable parts, to assembly lines then to automated assembly lines, things now develop more and more each day, those pictures are now just for present_ness, for now_ness, not for future_ness.

I know there is one kind of pain for which nobody has yet found a cure-the pain of that comes from the ending of a relationship. It could be anything, marriage, love affair, deep friendship; in fact any strong emotional tie between the two people.
Yes, it is true that no cure has been found but people who have gone through this kind of broken relationship all agree that time is the great healer. How much time will vary from person to person, but it is 80% true that grief will last as long as the original relationship lasted. The sad thing all people have to admit is that when the breakdown occurs, we can only stumble forward over the stones beneath our feet, it is all dark ahead and we will fall painfully many many times before we begin to see the light at the end of the tunnel...

In all, there is NEVER ever ONE solution to any problems, it is just taking a few minutes, a few days, a few months or let it be a few years for one to find another truly BETTER solution, no one knows when it comes, but it surely comes !!!
Being stronger and more detemined, more consistent, especially MORE CONFIDENT is the most prerequisitte to get over all the obstacles ahead...At least I take it for granted...

[Tom Frohman]

Is vu hometown's latest login?

[Mick]

Originally posted by Tom Frohman
Is vu hometown's latest login?

true true..OK

[mandya]

Originally posted by Tom Frohman
Is vu hometown's latest login?

Vu is not hometown, Hometown is Fiona

I always admire his talent...

I still know who is boss and who is not...

[Tom Frohman]

vu=mandya=hometown?

[Mick]

Originally posted by Tom Frohman
vu=mandya=hometown?

true true OK I always admire his talent true true OK

[SolarFlare]

Tom Frohman==Tom Frohman?