dna determine body structure
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So, I don't know exactly how DNA does code for
the body plan, but I do know about the
mechanisms that it has which convince me that
it can code for any given body plan: these
mechanisms are powerful enough to do so, even
if we don't know exactly how human DNA uses
them.
So, first, transcriptional regulation. You know the
"central dogma": RNA polymerase transcribes
RNA from DNA, and ribosomes translate proteins
from RNA. (I'm not sure exactly what a masters
in pharmacology teaches, so I might explain
some things you already know, and also may
explain them for the sake of readers who don't
have that much biology background.) Now, where
an RNA polymerase starts and where it stops
transcription can be controlled. A start site
needs a promoter sequence, but a given
promoter can be regulated by transcription
factors, proteins which can bind to the DNA near
the promoter, or even bind to DNA a farther
distance away from the promoter but still have
an effect on that promoter. Some promoters are
not themselves sufficient for the DNA sequence
to be transcribed, but need activator
transcription factors to help, while some
promoters can cause the DNA to be transcribed
without assistance (except from RNA polymerase
and its helpers which are always present), but
can be stopped by certain repressor transcription
factors. Each transcription factor has a certain
DNA sequence that it binds to, and can affect
the transcription of genes where that sequence
is in the appropriate place, usually upstream of
the gene itself, or in an intron, or downstream.
This can get pretty arbitrarily complicated: you
can have a given gene A which can be affected
by activators B, C, and D, and repressors E, F,
and G, in such a way that gene A is only on if
either B is bound to it or C and D are both
bound, while even if the activators are bound it
will be turned off if E and F are both bound, or if
G is bound, except that if B, C, and D are all
present it will be transcribed even if G is, except
that G together with either E or F will turn it off
even if all three activators are present. These
transcription factors are themselves proteins,
coded for by DNA, meaning that DNA codes not
just for what gets transcribed and translated, but
when it gets transcribed and translated.
From regulation comes differentiation, or how
cells with identical DNA can behave differently.
Consider hypothetical proteins A, B, and C,
where "normally", C is expressed while A and B
are not. Furthermore, A activates B, B represses
C, and B activates itself (which is both perfectly
legitimate and happens a lot). If A gets produced
briefly (worry about how that happens later),
then it will activate B and produce a bit before it
goes away. That B will activate the production of
more B, eventually reaching a stable level, as
well as repressing C, and will stay that way
unless something later interferes. This cell has
now changed from a cell expressing C and not B,
to a cell expressing B and not C. If B and C
each were transcription factors that affected the
production of a number of other proteins, this
can cause a fundamental change in the behavior
of a cell. In fact, that's what often happens:
different cell types, such as muscle cells and the
various types of blood cells, have "master
regulator" proteins which (a) promote their own
expression, (b) repress the expression of other
types' master regulator proteins, and (c) activate
the expression of the proteins necessary for a
cell to behave like the cell type in question.
Second, signalling. Some proteins are receptors,
which (for example) have a transmembrane
domain with parts on both sides of the cell
membrane, such that the binding of a certain
signal molecule/ligand to the part outside the
cell triggers a conformational change in the
entire protein, which is then detected in the part
inside the cell. "Detection" might mean, for
example, that the new conformation of the
intracellular domain can act as a kinase,
phosphorylizing a transcription factor causing the
transcription factor to change conformation, such
that only the new conformation can actually act
as a transcription factor. There are other
mechanisms that accomplish the same general
pattern: DNA can implement conditional logic.
For example, by constantly expressing proteins A
and B, where A is a receptor which, on binding
ligand X outside the cell, phosphorylates B, and
B is a transcription factor which, when
phosphorylated, activates C, you have DNA, and
only DNA, coding the behavior: "if X is present
outside the cell, produce protein C".
The ligands that cells' receptors detect can be
naturally occurring environmental molecules,
allowing cells to react to what's around them, or
they can be molecules emitted by other cells for
the express purpose of acting as a signal.
the body plan, but I do know about the
mechanisms that it has which convince me that
it can code for any given body plan: these
mechanisms are powerful enough to do so, even
if we don't know exactly how human DNA uses
them.
So, first, transcriptional regulation. You know the
"central dogma": RNA polymerase transcribes
RNA from DNA, and ribosomes translate proteins
from RNA. (I'm not sure exactly what a masters
in pharmacology teaches, so I might explain
some things you already know, and also may
explain them for the sake of readers who don't
have that much biology background.) Now, where
an RNA polymerase starts and where it stops
transcription can be controlled. A start site
needs a promoter sequence, but a given
promoter can be regulated by transcription
factors, proteins which can bind to the DNA near
the promoter, or even bind to DNA a farther
distance away from the promoter but still have
an effect on that promoter. Some promoters are
not themselves sufficient for the DNA sequence
to be transcribed, but need activator
transcription factors to help, while some
promoters can cause the DNA to be transcribed
without assistance (except from RNA polymerase
and its helpers which are always present), but
can be stopped by certain repressor transcription
factors. Each transcription factor has a certain
DNA sequence that it binds to, and can affect
the transcription of genes where that sequence
is in the appropriate place, usually upstream of
the gene itself, or in an intron, or downstream.
This can get pretty arbitrarily complicated: you
can have a given gene A which can be affected
by activators B, C, and D, and repressors E, F,
and G, in such a way that gene A is only on if
either B is bound to it or C and D are both
bound, while even if the activators are bound it
will be turned off if E and F are both bound, or if
G is bound, except that if B, C, and D are all
present it will be transcribed even if G is, except
that G together with either E or F will turn it off
even if all three activators are present. These
transcription factors are themselves proteins,
coded for by DNA, meaning that DNA codes not
just for what gets transcribed and translated, but
when it gets transcribed and translated.
From regulation comes differentiation, or how
cells with identical DNA can behave differently.
Consider hypothetical proteins A, B, and C,
where "normally", C is expressed while A and B
are not. Furthermore, A activates B, B represses
C, and B activates itself (which is both perfectly
legitimate and happens a lot). If A gets produced
briefly (worry about how that happens later),
then it will activate B and produce a bit before it
goes away. That B will activate the production of
more B, eventually reaching a stable level, as
well as repressing C, and will stay that way
unless something later interferes. This cell has
now changed from a cell expressing C and not B,
to a cell expressing B and not C. If B and C
each were transcription factors that affected the
production of a number of other proteins, this
can cause a fundamental change in the behavior
of a cell. In fact, that's what often happens:
different cell types, such as muscle cells and the
various types of blood cells, have "master
regulator" proteins which (a) promote their own
expression, (b) repress the expression of other
types' master regulator proteins, and (c) activate
the expression of the proteins necessary for a
cell to behave like the cell type in question.
Second, signalling. Some proteins are receptors,
which (for example) have a transmembrane
domain with parts on both sides of the cell
membrane, such that the binding of a certain
signal molecule/ligand to the part outside the
cell triggers a conformational change in the
entire protein, which is then detected in the part
inside the cell. "Detection" might mean, for
example, that the new conformation of the
intracellular domain can act as a kinase,
phosphorylizing a transcription factor causing the
transcription factor to change conformation, such
that only the new conformation can actually act
as a transcription factor. There are other
mechanisms that accomplish the same general
pattern: DNA can implement conditional logic.
For example, by constantly expressing proteins A
and B, where A is a receptor which, on binding
ligand X outside the cell, phosphorylates B, and
B is a transcription factor which, when
phosphorylated, activates C, you have DNA, and
only DNA, coding the behavior: "if X is present
outside the cell, produce protein C".
The ligands that cells' receptors detect can be
naturally occurring environmental molecules,
allowing cells to react to what's around them, or
they can be molecules emitted by other cells for
the express purpose of acting as a signal.
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