Re: Flagellum linkage

On Tue, 03 Jul 2007 08:31:22 -0700, hersheyhv <hersheyh@xxxxxxxxxxx>
wrote:

On Jul 3, 10:25 am, *** <remdic...@xxxxxxxxxxxxx> wrote:
On Mon, 02 Jul 2007 11:51:18 -0700, hersheyhv <hersh...@xxxxxxxxxxx>
wrote:



On Jul 2, 10:52 am, *** <remdic...@xxxxxxxxxxxxx> wrote:
On Sun, 01 Jul 2007 07:43:24 -0700, hersheyhv <hersh...@xxxxxxxxxxx>
wrote:

On Jul 1, 10:05 am, *** <remdic...@xxxxxxxxxxxxx> wrote:
On Sat, 30 Jun 2007 15:25:36 -0700, hersheyhv <hersh...@xxxxxxxxxxx>
wrote:

On Jun 30, 10:22 am, *** <remdic...@xxxxxxxxxxxxx> wrote:
I am very impressed with various serious discussions about evolution
by linkage if proteins with pre-existing functions. I have enjoyed the
give and take. I have no technical ability so I will talk with the
car analogy in mind. I am unable to decipher the linking of
pre-existing functional proteins with the transition from a bacteria
to the flagellum.

There are two completely independently evolved bacterial flagellum
that utilize the function of rotating a whip to generate motility. In
both cases (the archaean and eubacterial) there is a linkage of a
rotatable whip structure to motive force that causes movement at a
distance either by cleavage of ATP or by protonmotive forces.

It seems to me the idea of linking pre-existing functions such as a
motor, drive shaft and wheels together is very over simplified.

Not oversimplified even for the invention of the automobile. The
invention of the automobile involved merely the linkage of a motor
subsystem (previously invented for purposes other than producing an
automobile) and an unmotorized wheeled cart (previously invented for
purposes other than producing an automobile) by a simple linkage of
the motor to the wheels without any significant change in either the
unmotorized wheeled cart or the motor.

I was thinking of the difficulty of getting compatibility. Ford and
GM parts share functions, but interfacing those functional parts just
doesn't happen.

This is not a problem for the invention of a flagella by linking a
motor subsystem to a rotatable pore via a chimeric protein linkage.
Proteins are chains of amino acids and the chemistry of linkage is the
same for every link in the chain. Similarly, DNA is a chain of

I understand the nucleotide chemistry is standardized, but the form
(structure?) varies depending on the sequence.

The 'form' of DNA is a double helix regardless of sequence.

I was sloppy. I was thinking of the gene and subsequent protein as
one. Gene sequence translates into a protein which has form
determined by folding with resulting electrochemical charges.

Probably sloppy again, but it is how I currently picture the process.

Isn't it amazing that the DNA "knows" what sequence to select (I know,
DNA only holds the instruction set, but one of those instruction sets
makes the protein that reads the gene of interest and know what to do
with the gene)

DNA doesn't "know" anything. Not any more than an "encyclopedia" that
never leaves the library "knows" what its contents are. It is a
passive storage device from which particular subsets of data are
extracted (by a copying, called transcripiton, into a mRNA) and this
(sometimes after manipulation, especially the removal of introns in
eucaryotes) is then translated into protein.

The computer "knows" how to find its components and instruction sets
to access those components, that is how I am understanding DNA
"knows." That is why I used quotes around "knows."

It helps if you can validate what I get right, it encourages me to
keep trying.

DNA is imperfectly replicated (without the imperfection of
replication, there would be no evolution). It has subsegments that
are transcribed into RNA based on its interaction with proteins that
bring in information from the environment. Proteins bind to it, often
in particular spots based on the sequence that is exposed in the major
groove of the helix. That's it.

Funny "without imperfection of replication, there would be no
evolution" is the very basis for my questions. I know we all start
with the assumption that somehow DNA came into existence with its
double helix (what a remarkable condition), and somehow it has the
means to divide and become two cells with identical DNA. But how
changes which alter the DNA itself seems unanswered. A transcription
error would seem to not change the DNA.

I assume the form is
vital to key into source and destination of a protein and allow
transfer of whatever payload is involved.

Not a good analogy. DNA sequence is a linear code that gets
translated into a linear code of aa sequences. It is (largely) this
linear code that determines the folding of the protein. There is no
"payload" involved.

If my current description varies too much from yours above, then
phrased. However, I am of the impression that every action taken by
the various agents of the DNA are instructed by genes of the DNA.
Attraction and repulsion after folding form the basis for the
functional specificity.

I am way over my head. As I read books

Which books? You need a college level textbook in genetics or
molecular biology.

Wouldn't help me. I keep a copy of Gould's latest Evolution 2002. My
ability to memorize is terrible and I have reached an age where it is
only going to become worse. For some reason I retain logical
relations, but can't hold onto the words which contain the thoughts so
I beat around with make do words.



and the threads of t.o. I pick
up ideas.

I would be very cautious about *some* of the ideas that one can pick
up on t.o. Regard creationist ideas as toxic waste until you can
verify them. But because the people who *actually* know something
often are posting here quickly, they too sometimes use sloppy language
that can be confusing or language that goes over the heads of some
readers. I certainly have been (and will undoubtedly continue to be)
guilty of this.

As I don't memorize, dangers are lessened. New ideas must meld with
those that I have accepted or overturn them. I am so grateful to you
and Sean and those others that have entered into the recent threads,
I love the display of differing thoughts. I then keep what adds to
my understanding. No worry, I also have a hard time reaching
decisions, so I am constantly arguing both sides in my own head.


Presenting my current take of those ideas gives me
feedback. I do hope there are lurkers that appreciate your efforts to
educate.

t.o. does not substitute for a more formal and disciplined education
in molecular biology.

I understand and agree. However, I had to pick courses in which I
could achieve. Some subjects don't rely so heavily on memorization.
In real life I have done some amazing things, often with computer aid.
I can program because the program crashes when I make mistakes.
Failure as a path to success. I had some technicians working for me.
They found faulty parts by "memorizing" what signals to expect at
various key points. I couldn't do it. I don't get pictures in my,
let alone be able to memorize them. BUT, I was able to use a computer
to single step through a known program and verify a signal's presence.
None of my people could do that.


nucleotides and the chemistry of linkage is the same for every link in
the chain. Producing a chimeric protein that has one 'GM' end and a
'Ford' end simply involves clipping a DNA chain of the GM gene and
attaching it to a different nucleotide of a clipped Ford chain using
the chemistry that is used by both Ford and GM. No fancy soldering or
welding is required.

We are not talking about "chimeric" proteins in nature, are we?

Yes. Such proteins are rather common. And are often a mechanism for
generating 'novel' [actually new combinations of old] functions.

http://en.wikipedia.org/wiki/Chimera_(protein)

see http://en.wikipedia.org/wiki/Fusion_protein -- keep in mind that
wiki is not always accurate and in this case only lists fusion
proteins that are linked to cancers. Other, non-cancer, examples of
chimeric or fusion proteins include antifreeze proteins in arctic
fishes. And many proteins have undergone internal duplications of
moieties.


"Fusion proteins, also know as chimeric proteins, are proteins created
through the joining of two or more genes which originally coded for
separate proteins. "

Thanks, this gives me a useful understanding.

Fusion proteins occur naturally and, of course, can also be produced
by humans now.

Your use of chimera to refer to natural proteins is confusing to me.
Manmade or in vitro reproduced (my understanding from Wiki) seems more
narrow a definition and a useful way to separate nature's action from
man assisted.

It
seems to me that at least 2 mutations in one gene neither causing
deletion nor destruction of the protein: The specific mutation of a
"Point" (AA?) and alteration of form and charge of the mating end/s.

Deletion of intervening sequence, as described, is a single mutational
event. The types of mutations that can occur are point mutations
(change in a single nucleotide), insertions (adding one or more
nucleotides), deletion (removing one or more nucleotides),
duplications (where a segment of DNA gets duplicated), ploidy changes
(where the number of chromosomes changes), and rearrangements
(translocation, inversion) where DNA is neither gained nor lost, but
the order of sequence is changed. If this sounds unfamiliar to you,
you do need to look at a basic molecular biology or genetics textbook
before continuing on.

The mutation types are familiar to me although the mechanics are
vague. I can see a single AA changing from one acid to another (well,
not really),

Changing a nucleotide at the level of DNA changes the codon, the bit
of information which (after transfer to mRNA) determines what aa is
put in during the translation of the information to protein. Because
the genetic code is degenerate (meaning that more than one 3-letter
sequence codes for the same aa when translated into protein), not all
single letter changes produce a change at the level of the encoded
protein. But some do. The functional consequences of such a change
in a single aa can range from nothing (the change has no functional
consequence) to modifying function to changing the amount or rate of
function to stopping further protein synthesis (mutation to a stop
codon).


But changes after the mRNA copies the portion of DNA does not alter
the DNA, thus no mutation in new cell.

I am lost with the many abbreviations (I know there is a right word,
but can't think of it. I am thinking of mRNA, codon, nucleotide, etc)
Sorry, but I best not take more of your time. I think I will go back
into lurk mode.



deletions and insertions seem more vague,

Read up. Deletion/duplication is often a consequence of error at the
level of recombination. It can also occur due to cleavage of the DNA
double helix and its re-attachment of the 'active' bare end.
Insertion is typically due to transpositional elements that can 'move'
from one site in DNA to another. Such elements include 'viruses' like
HIV.

I hope someone is following this thread and can gain from it. I feel
like you are scratching the right spot, but I can't combine the
individual concepts. "cleavage of the DNA double helix" I don't
understand, then re-attachment. "'move'" from one site in DNA to
another", I didn't know DNA changes except by mutation. OK, "germline
mutations." When the helix separates and duplicates into a new cell
why should there be any mutation?

Sorry, I am lost in the many, many concepts. Behe is so good about
repeating meaning of concepts. I don't know about his conclusions,
but he seems to anticipate my kind of reader.


and change of
location or duplication very unlikely.

Chromosomal translocations and inversions are among the most common of
observable mutational events. That is because such events, although
affecting a large visible chunk of DNA, often have no functional
consequences. Only errors that result in aneuploidy (specifically
trisomies but not monosomies) or polyploidy are more common.

Total loss on me.


I expect chemical changes to
be predictable. What is the agent/s of change/mutation? How can
"stuttering" "duplication", "Insertions" and "inversions" possibly
happen with so many safeguards to DNA changes in place.

Evolution actually 'optimizes' the rate of mutation. The downside of
safeguards or repair systems is that they slow down or even stop
replication. And faster replication is desirable, so long as the
amount of error is not 'too large'. This is a mini-max problem. The
more you prevent errors, the slower you grow. So you have to find the
optimum balance between fast growth and the amount of error that is
'permissible'.

I thought life cycle determined mutation rate. More generations per
cycle period (year) more mutations. Computers constantly test for
errors such as parity and checksums. It is part of the process. Is
it the process that slows the rate of mutation or the corrections?

How can the cell know whether an error is 'too large'? "Optimum"
sounds like "choices"? I wouldn't think cell duplication would
involve choices (permissible).

My computer changes binary bits and must detect the error and reread
the memory, but that is a purely electrical activity. Perhaps due to
a weak memory cell output. The error nor the rereading does not alter
the memory cell content. I am of the impression, the DNA is "Read
Only Memory" with modifications happening during transcriptions as
various genes are expressed. Such modifications do not alter the DNA.

No. Error or damage to DNA can occur at *any* time. Some errors are
more likely during transcription, others are more likely during
replication, others (damage from cosmic rays and UV) can occur at any
time. Some error is simply due to chemistry. For example, the
spontaneous deamination of the base cytosine in DNA produces the base
uracil.


I sure wish I had your lexicon in my head. You suggest so many
interesting concepts. I can understand errors during cell division,
but "transcription", to me, means taking information (reading DNA)
from DNA as a meaningful gene and changing the contents into some
useful form. Can reading the DNA modify the DNA?

Mutation of the DNA, the basis for changes on which NS can take place,
seems very much harder than a simple binary computer change.

Cytosine deamination, the switch between the enol and keto form of
hydroxyl, cleavage of chemical bonds by radiation, etc. are occuring
all the time.

Students are used to "learning" by memorizing. Since I learn to
satisfy my mind, I "learn" by reason. Frustrating for you and me.

I don't want you to "learn" by memorization. But I do need you to
learn by a disciplined and efficient method that doesn't try to re-
invent the wheel and entirely new language to describe it. Hie thee
to a text book. Any college text on genetics or molecular biology.
Read it. Ask questions. Figure out what they are really saying.

Unfortunately the lexicon of biology and associated sciences is huge
and subtle. Also, the language of biology is based upon assumptions
that I am questioning. The fact I am not learning means things aren't
sticking. Perhaps it is age.

I give you an A for effort.


Every time I try to be specific I find more complexity to achieve even
the simplest modification in a way that promotes neutrality or
survival.

I am currently questioning if you know enough to be able to say that
with any reason.

I certainly am limited by not having the lexicon down pat. I
substitute general vocabulary where the exact term would be less
confusing. I am surprised you have been so generous so far and would
understand if you were tired of my fumblings.

The solution is to learn the lexicon and what the terminology means
*by reason* but not from scratch.



Also, I wonder how the joining of functional proteins can happen
through random mutation.

Deletion is one mechanism. Imagine a gene that produces a protein
that protrudes from the rotatable pore and is tightly connected to
it. Let's call it a 'tooth' or 'cog' protein. The gene that encodes
this protein has an amino end that is part of or is attached tightly
to the outside of the pore. The carboxy end is sticking out. So that
gene encodes in the following way: N-xxxxxxyyyyyyyy-COOH. Just
downstream we have the gene that interacts with, and is pushed by, the
motor system, but has no interaction at all with the pore. The motor
subsystem is, remember, doing something else in the cell, not pushing
the pore around in circles. Let's call this protein a 'camshaft'
protein. It is encoded in DNA as N-aaaaaaaazzzzzzz-COOH. The z end
is the end that is pushed by the motor. The a end does whatever this
motor does in the cell. The DNA that includes both of these genes is:
N-xxxxxxyyyyyyyy-COOH bbbbbb N-aaaaaaaazzzzzzz-COOH

where b is simply DNA sequence between these two genes. Now we have a
deletion occurring to produce:

N-xxxxxxyaazzzzzzz-COOH

or

N-xxxzzzzz-COOH

or

N-xxxxxxyyyyyaaaaazzzzzzz-COOH

I get lost in the formalization

There could be any number of such chimeric genes that might have
useful function.

Now if you look at the above chimeric gene and what it codes for, what
you see is that all the above proteins produced still have the xxx end
that binds tightly to the pore and also a zzz end that is recognized
and moved by the motor subsystem. Now when the motor subsytem moves
the z end, it is pushing the tooth or cog of the pore and causing it
to rotate.

As I understand "chimeric genes" they are man made. If I am right,
introducing them into my questions just confuses me.

Anything that man can do with genes already occured in nature.
Chimeric genes are not at all impossible by purely natural mechanisms
that do not require human intervention.

The pore and the whip mutations need to
happen in a time frame. Mutation of a pore to allow a whip/filament
to penetrate enough to protrude outside the cell must happen when such
a filament is also mutated to enter that pore.

Bacteria commonly produce proteins that extrude from their surface.
Many are pilins (the source of the whip of archaeal flagella). Some
are open tubes that can act as injectors of toxins (the likely source,
although some bacteriophage coat proteins are another possibility, of
the whip of eubacterial

...

read more »



I have to be content to understand what I understand and keep looking
for enhancement. However, part of my problem is Sean et al ask the
questions I have and do seem to have the lexicon. I try reading the
references, but the technical language is too foreign. I suspect
conclusions are buried in the terms such as the discussion of "multi
dimension" versus "3 D". As I tried to grasp the reference paper it
seemed to me to say it had focused on the most likely proteins, but
allowed there were many more uncommon proteins, thus supporting what I
think Sean was saying. However the paper and much of what Sean argued
was far beyond my understanding. I am still wrestling by the use of
"multi dimension" as related to the transcription process. I think of
folding and the process creating dimensions as part of the folding.
As you can see, I just muddle through.

Thanks for your time and effort.

.

Loading