[ Follow Ups ]
Posted by Pierre (discussion with J. Edser originally on sbe) on September 04, 1999 at 03:48:56:
J. W. Edser
7qmvrk$djg$1@darwin.ediacara.org...
> > >>PS:-
> > >> The selected unit problem might arise because we are not
able to
> > >> reconstitute the evolution, ie historical relationships
between
genes,
> > >> cells and organisms. The origin of multicellular
organization, the
> > >> mechanics of embryonic development as well as the origin of
> > >> the "genetic
> > >> code" (ie the DNA/protein interdependence) are not
known.
> > >> Of course gene
> > >> centrists propose that everything started with genes (RNA)
floating
in
> > >> the
> > >> primitive ocean, whereas organisms centrists cannot
efficiently
> > >> address the
> > >> problem, because organisms are too late.
>
> > >JE:-
> > >I think these genes must have been contained
> > >in membranes rather than just free floating.
> > >In this way they were proto organisms.
>
> > PS:-
> > The proto organism you mentioned with a membrane containing genes
> > is a proto
> > cell. I am not sure the proto cell was empty when genes appeared.
Genes
> > might be a late invention of proto cells already full of
> > proteins. There are
> > multiple reasons for that, the most important is the impossibility of
> > ribonucleotide synthesis in prebiotic conditions. According to
current
> > knowledge, RNA and DNA need proteins to be made, whereas it is
> > very easy to
> > obtain proteins from free amino acids. Amino acids are abundant in
stellar
> > materials.
>
> JE:-
> The main point here for me, is that the same
> gene/s or proteins outside of the proto cell
> unit, have nothing to do with the gene/s proteins
> selected within the protc cell unit. Thus its the
> membrane bag that makes the process of selection
> here, at all possible.
>
> > PS:-
> > In addition, we have to realize that RNA is a polymer of ATP and
other
> > ribonucleotides. ATP and other NTPs require a very active metabolism
(most
> > probably based on photosynthesis) to accumulate. Do you understand
why
the
> > cell uses such a precious energetic currency (ATP), to store
> > information ?
>
> JE:-
> I am not a biochemist and would like
> an answer that a non specialist can
> understand.
> What are NTPs?
I am afraid there is no answer, even for a specialist, about this strange
association between energy and information in nucleic acids. Interestingly,
before the discovery of the role of nucleic acids in heredity, they were
considered as a stock of ATP (adenosine triphosphate) and other NTPs . NTPs
stands for nucleoside triphosphate : ATP, UTP, GTP, CTP, ie the basic
components used to make RNA.
> > PS:-
> > I
> > think nucleic acids participated energy storage and management
> > before being
> > recruited for "information". I call this idea the
DNA-glycogen
hypothesis.
> > RNA is to NTPs what glycogen is to glucose, or proteins to amino
acids
or
> > fat to reduced carbon ...
>
>
> > PS:-
> > Of course I realize that, if genes came late in the photosynthetic
> > protocell, we have to find a solution for reproduction. I have some
ideas
> > that might be long to develop, but the key is to see mitosis of the
> > protocell as a growth by accretion/accumulation (cristal-like)
> > followed by a
> > break along a symmetry axis. No need to reproduce, just growth and
break.
> > That's more tricky for proteins. I can develop later if you wish.
>
> JE:-
> The membrane bag just too full and broke into two unequal parts?
> Are there possible reasons for why and how?
Why UNequal ? Mitosis of the cell is division in equal parts. If the
protocell is too big, its mechanical resistance goes down and it breaks.
That's it. For the same reasons, it's easier to break a long branch than a
short one, or to break a big soap bubble than a small one.
> > >JE:
> > >I have often pondered the question that the cell may be the unit
> > >of selection in nature (the unit of maximal reproduction).
> > >It is a fascinating concept.
> > >It seems to me that the genes are read by at least a
> > >cellular unit. The question is, does what is read mean
> > >more than what is doing the reading? Is the tape more
> > >important than the tape recorder?
> > >What is their relationship to each other within the logic
> > >of selection.
>
> > PS:-
> > I am more and more convinced that cell is the selected unit. The
constant.
> > c, for cell and speed of light :)
>
> JE:-
> This means to me that the cell for you, is the unit
> that is constantly reproductively maximized in nature.
Exactly
> > PS:-
> > If cell is the selected unit, it includes genes. Is it possible to
define
> > secondary units inside cells : tape or tape recorder ? Or is it
irrelevant
> > to dissociate further ?
>
> > >JE:
> > >The step from one to many cells, is an enormous
> > >selection problem. The cell that divides is 100%
> > >efficient in turning itself into reproductions of
> > >itself, since nothing is left over that has to
> > >die. As soon as you have multicells, then a soma
> > >is produced that must "die". This constitutes a
> > >waste i.e. a lowering of reproductive efficiency
> > >below the 100% of single cell fission.
> > >This problem is tied in with why multicells evolved in
> > >the first place, when multicells are less efficient in
> > >reproducing themselves than single cells are.
> > >The advantage must be the muticells ability to better
> > >adapt to niches prohibited to single cells at the
> > >time e.g. most dry land.
>
> > PS:-
> > I agree that cell centrics requires a theory of epigenesis based on
> > "selfish" cells to build the embryo and the organism. JJ
Kupiec
developed
> > such a theory long ago. (If you need details, visit
> > www.heraclitean.com, in
> > the essays and references sections). Kupiec's theory briefly is :
> > because of
> > "food" limitations in a growing population of cells, and because
of
> > diffusion of nutrients and wastes, metabolic niches appear and cells
> > specialize by adaptation to these niches. It leads to
autoorganisation
of
> > the cell colony. Bacteria also specialize and organize when grown to
large
> > colonies on Petri dishes (many papers by J. Shapiro).
>
> JE:-
> You may like to refer to the "Contained Reproducer Selection
Problem"
> that I have posted to sbe and explain how the above fits the three
> possible reproductive strategies.
>
> > PS:-
> > For example, imagine that cells grow and form a colony on the top of
solid
> > nutritive media. The nutrients diffuse into the colony. The cells
> > at the top
> > of the colony lack food and starve. Diffusion thus puts a limit to
the
> > colony size. Imagine that cells at the top adapt to use wastes of the
> > bottom layer. The colony can grow further. And so on for the next
layers,
> > depending of the number of possible specializations. This number
might
be
> > equal to the number of reactions in the metabolic chain. In early
embryos,
> > or nematods, everything starts with layers/rings.
>
> JE:-
> Is there any evidence that cells in these layers/rings use
> each others wastes as a resource?
In J. Shapiro large colonies, bacteria develop complementary metabolism
according to their positions. In the center of the group food is different
than at the edge and metabolism is adapted to these differences.
The mammalian organism is full of such reciprocal exchanges. The best
example is between aerobic (metabolic use of oxygen) and anaerobic (oxygen
is absent) cells. In many tissues you have aerobic cells around the arteries
bringing oxygen from the lungs and anaerobic cells at a distance, around the
veins. This is the case for example in the liver, or in the brain.
Schematically, anaerobic cells use glucose and produce lactate. These
reactions are more efficient in the absence of oxygen. Lactate is then
burned by aerobic cells into CO2 and H2O (mitochondrial Krebs cycle) This
latter reaction requires oxygen. Lactate, a waste of anaerobic metabolism,
is efficiently used by the aerobic layer of cells.
Thus, the presence of oxygen allows more symbiotic associations between
cells. Interestingly, apparition of multiple multicellular patterns
coincides with a rise in atmospheric oxygen, in the Cambrian.
Another information. In nematods where all segments appear morphologically
similar, there are metabolic differences. pH and CO2 for example form
gradients from head to tail. This is old data (1930's) unfortunately
forgotten. Modern molecular biologists do not cut centipedes in segments to
measure pH one hundred times. They sequence billion nucleotides of DNA.
> > >> PS:-
> > >> When we think (are selected to think), what is a neuron
doing
> > >> (selected for) ? Is the neuron just obeying the genetic
program
> > >> of thinking
> > >> ? What kind of selective advantages is the neuron obtaining
> > >> from obeying
> > >> such a program ?
>
> > >JE:-
> > >Certainly, if each neuron is the actual unit of selection,
> > >then it must produce a reproductive advantage to be selected.
> > >Neurons don't reproduce (?) so this presents an enigma, for
> > >the cell centric view.
>
> > PS:-
> > Neurons are at the very top of the growing cell colony. They have to
send
> > roots to the bottom to get some food ! By doing this, they
"detect" what
> > occur at a distance. In the same manner in a tree, leaves
"know" whether
> > there is water at the tip of the roots. In a sense, roots convey
> > information
> > to the leaves.
> > Neurons stop reproducing only in the adult after obtention of a brain
> > containing billion neurons. Why do they stop ? The reason is
> > obvious : they
> > reach a maximum population size given the resources thay have access
to.
> JE:-
> What is the evidence for your supposition here?
> If neurons are given excess food "in vitro" do they resume
growth?
> Does excess food and oxygen pumped into nervous tissue "in
situ",
> start neuron reproduction?
In animals, most often the limiting nutritive resource is protein. Animals
develop specialization in protein capture (vegetarian, carnivorous ...)
Thus, it is not a surprise that resources able to induce neuron growth in
vitro are proteins. Nor that neurons are specialized in protein capture :
they prefer proteins from the Nerve Growth Factor (NGF) family. In cell
culture, nerve growth factor makes neurons crazy. They grow dramatic hairy
"roots" and may reproduce.
During embryonic development, nerves (extensions/roots of neurons)
accumulate at the sources of Nerve Growth factor and compete for this
protein. Many neurons die. The number of surviving neurons is precisely
determined by the amount of nerve growth factor produced by cells present
at the extremity of the nerve. In situ, interesting results have been
obtained in animals. In humans, clinical trials are ongoing to use Nerve
Growth Factor in medecine to repair destroyed nerves or to cure some
degenerative brain diseases.
Nerve growth factor is related to a family of growth factors, called
cytokines.
Interestingly, in the prevalent view, growth factors and cytokines are not
considered a limiting nutritive resource. They are thought to induce a
molecular signal by binding a specific receptor at the cell surface. The
signal produced by the receptor is thought to be transmitted through a
molecular cascade, to switch on specific genes. Such specific cascades and
genes have been the subject of intense research for years, but nothing clear
emerges.
A quotation from http://www.heraclitean.com/hbg/essays/immunometab_sonigo/
Reading is optional. If tired/busy goto end of quotation.
"Would alimentary specialization at the cell level be sufficient to
explain
the diversity and functions of cytokines and cytokine receptors ? Some
answers might come from comparison of animal cells with multicellular
animals. Although amino-acids are essential building blocks, their synthesis
is unequally distributed amongst the living world. It requires for example
nitrogen fixation, a central element in ecosystem formation (25,26). To a
greater extent than glucids or lipids, amino-acid and proteins often
constitute a limiting resource in the animal kingdom. Animals obtain
amino-acids from other organisms rather than by de novo synthesis. In this
case, amino-acids will not be captured as free molecules, but included into
proteins. Although life uses a limited number of amino-acids, diversity of
proteins is susceptible to generate a large variety of food specialization.
Animals are indeed adapted for efficient capture of the most abundant
protein food in their proximity. For example, some are specialized for
vegetal proteins capture, other for animal protein capture. It seems that
animals are entirely built around this specialization : teeth, digestion
apparatus, locomotion apparatus, metabolic equipment often reflect protein
specialization (vegetarian, carnivorous ...).
In the same way, cells might be adapted to the most abundant protein
resource in their proximity, as reflected by the specialization of their
surface receptors. Just like animals, cells are limited by an hydrophobic
"
skin " (lipid membranes) which represents a barrier to hydrophilic
substances. Cells had to develop a dynamic system of protein capture using a
wide ensemble of " sticky " proteins located at the membrane. These
membrane
molecules, specialized in binding and internalization of aliments,
especially proteins, are exemplified by members of the immunoglobulin
superfamily (27). This superfamily is one of the most diverse and abundant
protein family. It includes for example adhesion molecules (see also below
for adhesion and apoptosis), and cytokine or olfactory receptors.
Interestingly, some receptors are related to amino-acid transport proteins
(for a recent review, see ref. 28). Finally, what we call a cytokine
receptor might be considered as a specialized tool for capture of proteins
from the cellular microenvironment. If proteins constitute a limiting
resource in the cellular world, like in the macroscopic world, successful
capture will condition cellular activity. Would cells be more complex than
multicellular animals ?
End of autoquotation :)
> > >> PS:-
> > >> Cell centrics is usually intertwingled of
> > >> gene centrism and organism centrism. For example, the clonal
selection
> > >> theory of antibody formation, a paradigmatic application of
> > >> darwinism at
> > >> the cell level, considers that cells are selected by a
signal from
the
> > >> organism, designed by the required defense from infections !
As
> > >> you already
> > >> mentioned, this is a strange multi selected unit conception
here. The
> > >> cell
> > >> is the selected unit, but the selective force is at the
> > >> organism level !
>
> > >JE:
> > >It appears to me that the cell, as an assumed unit of
> > >selection, is being used as a model and organism
> > >selection the theory, it was derived from.
>
> > >>PS:-
> > >> This is why the clonal selection theory in immunology, as
well as
many
> > >> modern physiological interpretations are wrong. Rethinking
physiology
> > >> requires rethinking the mechanics of embryonic development.
> > >> For this, we
> > >> have to forget our anthropocentrism, and just consider cells
as
> > >> independant
> > >> animals obeying not a program that represent ourselves, but
> > >> the rules of
> > >> evolution.
>
> > >JE:
> > >Yes, if the cell is an actual i.e. not a modeled unit
> > >of selection, organisms must then become a by product of
> > >"selfish" cells.
>
> > PS:-
> > I proposed that adaptation and competition between selfish cells to
eat
> > microorganisms invading the organism are sufficient to explain the
complex
> > structure and organization of the immune system.
>
> JE:-
> Epistemologically this is a model of the Darwinian fertile
> organism unit i.e. a useful simplification that gives
> you an experimental handle on the problem. Any results
> from this model must be reworked via the theory it was
> derived from, as a simplification, otherwise the model
> is misused.
You mentioned that cell centrism has been used as a model of the darwinian
fertile organism. Like in the clonal selection theory for antibody
synthesis. But if we consider cell as THE selected unit, and that such
selection is driving organism organisation, is it a model or a variant
theory ?
P