Re: COMPARATIVE VERIFICATION OF A GENETIC AND AN EPIGENETIC MODEL

On Mar 3, 11:16 am, John Harshman <jharshman.diespam...@xxxxxxxxxxx>
wrote:
CNCa...@xxxxxxx wrote:
On Mar 2, 11:33 am, John Harshman <jharshman.diespam...@xxxxxxxxxxx>
wrote:
CNCa...@xxxxxxx wrote:
In the long discussion on the nature and origin of evolutionary change
no one came up with a case of a change in a gene or a regulatory
sequence that led to an evolutionary change in metazoan morphology.
Though only because you define such changes out of existence.

However, in response to my call for a detailed model of how a change
in a regulatory sequence might lead to such an evolutionary change in
metazoan morphology, on February 22, 2009 Mr. Harshman presented one
here in TO.
I'm toying with demanding that you call me "Dr. Harshman."

THE GENETIC MODEL OF EVOLUTIONARY CHANGE (Presented by J. Harshman on
Feb. 22 , here in TO)
"Of course there's a detailed model. It's pretty simple. A slight
change of sequence can produce a slight change in strength of a
transcription factor binding site, which in turn means that the gene
is expressed slightly differently, perhaps at a greater or lesser
concentration of the transcription factor. Similarly, a new binding
site can cause a gene to be expressed in a different tissue at a
different time, and loss of a site can cause it not to be expressed in
some tissue or at some time, both of which can cause changes in
morphology. Notice than none of these involve changes in the protein-
coding part of a gene, or its loss or inactivation. This is standard
evo-devo, which subject you might want to read up on."
Mr Harshman's model posits that such changes result from random
changes in regulatory DNA sequences.
Verification of the Harshman Model
1.The proposition that "A slight change of sequence can produce a
slight change in strength of a transcription factor binding site,
which in turn means that the gene is expressed slightly differently,
perhaps at a greater or lesser concentration of the transcription
factor." requires experimental/observational support.
Always nice to have, but why isn't it obvious? Unless you claim either
that 1) binding sites are nonexistent or have no relationship to DNA
sequence or 2) variation in sequence either leaves binding unchanged or
eliminates it altogether (i.e., binding is either on or off), the rest
is unavoidable. Do you indeed make either of these claims?

Speculations may not always be wrong but speculations can't be a
substitute for evidence when it comes to verifying a model. In the
absence of supporting evidence a model remains at best a model;
at worst it should be rejected.

You demanded a model. I gave you a model. Now you say that models are
pointless. I will note that you have never presented any real model,
just a lot of handwaving separated by large patchs of fog.

Yes you gave the model but you are unable to bring a single
evidence in its support. Should I consider it rejected?

2.The proposition that "Similarly, a new binding site can cause a gene
to be expressed in a different tissue at a different time, and loss of
a site can cause it not to be expressed in some tissue or at some
time, both of which can cause changes in morphology." can be validated
only by empirical evidence showing that
a. The change in the sequence of the regulatory
region can cause a differential expression of the gene in different
tissues.
b. The change in the sequence and the loss of the
binding site can cause changes in morphology.
Again, this is unavoidable if a) different species have different
binding sites for various transcription factors, b) transcription
factors influence tissue-specific expression, and c) binding sites are
necessary for transcription factors to operate.

Which of these do you doubt? Everything I claim is all standard
evo-devo, the result of decades of experimentation on gene regulation.

This is another way of saying "I can't find evidence to support
my model".

This is another way of saying "Why can't you google?"

No speculations on the possibility for such changes in the regulatory
sequences to occur can validate the model, only empirical evidence
can. The same criterion of the indispensability of experimental/
observational evidence for verifying each step of the proposed model
will be strictly applied to my model of epigenetic determination of
evolutionary change.
Does that mean you're actually going to present your model now? O joy!

I recognize Mr Harshman's right and benefit to change, correct and add
to his model supporting evidence in the course of this discussion. I
would also encourage other people here in TO to contribute to
improving Harshman's model and present other models (their own or
published) of genetic induction of evolutionary changes in metazoan
morphology.
This is a good point to note that it's not my model. It's the standard
model of evolutionary developmental genetics (evo-devo). It's been
developed over the course of many years in thousands of individual
studies. There are a fair number of books that explain this model. Sean
Carroll has written at least three of them.

You can improve and expand your model with evidence
from "thousands of individual studies" and from those three
books.

As could you. You seem unwilling to discuss this model. And you have
presented absolutely zero evidence for your model; in fact you haven't
even presented a model. The mechanisms of evolution and inheritance in
your scheme are quite obscure.

I have not read those thousand articles and three books.
"I have presented zero evidence." It happens to me too.
II can't see when I am nervous.


THE EPIGENETIC MODEL OF EVOLUTIONARY CHANGE IN METAZOAN MORPHOLOGY
The generalized model of induction of evolutionary morphological
changes in metazoans that I am presenting here is applicable mainly to
oviparous species, which have no other way for transmitting new
characters to the offspring but via the zygote (egg cell in
parthenogenetic organisms). In applying the model to viviparous
animals, and especially to placentals, direct, "real time"
transplacental influences of the mother to the embryo have to be taken
in consideration.
Description of the Epigenetic Model of Evolutionary
Change
Two important observations from paleontology and developmental
plasticity show a correlation between the environmental stress/stimuli
and changes in animal phenotype. An early paleontological observation
is that drastic changes in environment are correlated with
accelerated rates of evolution and diversification in metazoans. This
is the case with Cambrian (~550 Mya, with major shifts in the
climatic and geological conditions), the Ordovician (~500 Mya with the
drop of sea level and increased orogenic activity), Devonian (~380-360
Mya, with a paleontologically recorded sea retreat and related
climatic and ecologic consequences, such as colonization of land),
Permian (~250 Mya with hypoxic atmosphere), Cretaceous ( ~65 million
years ago with drastic climatic changes and increase volcanic
activity), Paleocene, Miocene and Oligocene, etc. An ever-increasing
body of evidence shows that in response to environmental stress/
stimuli metazoans develop new discrete phenotypic characters
without changes in genes and in many cases such changes are
transmitted to the offspring for one or more generations.
1.Adverse environmental stimuli can disturb homeostasis, thus
provoking stress condition that can affect the developmental
stability. Metazoans respond to environmental stressors with a stress
response. The stress response often leads to developmental instability
and ensuing changes in morphology, physiology, bahavior and life
history.
What does this actually mean? Where does
this stress response come from
and why did it evolve?

You have skipped the "Supporting evidence"
Read it below.

None of the "supporting evidence" answers my questions. But I agree that
scare quotes are appropriate here.

What is developmental instability, and how does
it result in fixed and heritable changes in morphology?

It does not. But, as transgenerational phenomenon it
facilitates induction of a change in the offspring.
There is sufficient evidence on developmental
instability. Isn't there?

That depends on just what you mean by it and what you are supposing it
can do. You seem to be imagining something on the order of Mayr's
"genetic revolution" applied to epigenetics. Accent on "imagining".

By that I mean exactly what I say: "There is sufficient evidence on
developmental
instability. Isn't there?"

Supporting evidence
Metazoans respond adaptively to drastically changed environment and
to stressful environmental stimuli by a neurally determined stress
response. The stress response in vertebrates is regulated by the
neuroendocrine circuit, the hypothalamus-pituitary-adrenal (HPA) axis.
In higher vertebrates, including humans, an additional central circuit
is involved, which receives stress signals and transmits them to the
amygdala, a part of the brain that is essential for the memory and
emotions, and determines the fact that in humans e.g., a stress
response often arises not only to real but also to perceived threats
"to the psychological or physiological integrity of an
individual." (McEwen, B.S. 1999. Stress. In: R.A Wilson and F. Keil
(eds.). The MIT Encyclopedial of the Cognitive Sciences, p.1).
An environmental factor is perceived as a stressor only when its
adverse effects exceed a neurally determined threshold, and its
perception and assessment takes place in the CNS. The final result of
the activation of HPA axis is the release of glucocorticoids into
blood, to which in a feed back process neurons in hypothalamus
respond by suppressing secretion of the stress neurohormone, CRH
(corticotropin releasing hormone) ( Miller, D.B. and O'Callaghan, J.P.
2002. Metabolism 51: 5-10).
In response to environmental stress the brain-HPA axis sometimes
induces adaptive morphological changes in whole populations. So,
e.g., in response to earlier than normal habitat dessication desert
amphibian tadpoles respond by an earlier (10 days, 26 instead of
normal 36 days) increased secretion of the stress neurohormone CRH
determining beginning of metamorphosis.
What do you imagine caused this particular stress response to evolve, as
opposed to any other imaginable responses to stress in that species? I
will note that in other species, a response to particular sorts of
stress can be delayed devolopment, diapause, and such. These are evolved
responses. How do they evolve?

You should not distract me now: How has stress response
evolved is not within the scope of my model which can't
be a "model of everything". My model is about the epigenetic
mechanism of evolutionary change in metazoans' morphology.

Yes, and I'm saying that these epigenetic mechanisms are an evolved
response to stress. The present action of these mechanisms has nothing
to do with evolution. The evolution is all in the evolution of the
mechanism, not in its operation. None of your "examples" have anything
to do with evolution.

Your nervousness makes you lose the common sense.

"The neuroendocrine stress axis represents a phylogenetically ancient
signaling system that allows the fetus or larva to match its rate of
development to the prevailing environmental conditions.. In diverse
vertebrate species, including humans, CRF (corticotrophin-releasing
factor -N.C.) and corticoids act both centrally and peripherally to
alter the rate of development in response to unfavorable
environmental conditions. This neuroendocrine response generates life
history transitions necessary for immediate survival." (Crespi, E.J.
and Denver, R.J. 2005. American Journal of Human Biology 17: 44-54).
Stress response also includes the stress-specific "fight or flight
response", which is also determined by processing of the stressor
(electrical spike trains into which it is converted in the nervous
system) in a group of specific hypothalamic neurons.
Stress response can induce changes in expression of genes especially
the heat shock factors (HSFs), which are necessary for the normal
development and such changes induce phenotypic changes and epigenetic
changes in chromatin. HSFs is believed to "link developmental programs
to
changes in chromatin. HSFs is believed to "link developmental programs
to environmental contingency" Rutherford, S.L. and Lindquist, S. 1998.
Nature 396:336-342). Shear stress (SS) modifies expression of a number
of genes by modifying histones H3 and H4 via acetylases and
deacetylases (Illi, B. et al. 2003. Circulation Research 93:
155-161).
The developmental instaability induced by environmental stressors in
metazoans is measured by the so-called fluctuating asmmetry (AS),
which was considered to be genetically determined by the level of
heterozygosity but analysis of empirical evidence has shown that
"the hypothesized correlation between level of heterozygosity and FA
is not met in this comparative analysis. Increased asymmetry of only
one of the transplanted populations seems to be caused by
maladaptation to the captive environment, rather than by varying
levels of heterozygosity, water quality, temperature or
density." (Vollestad, L.A. and Hindar, K. 2001. Biological Journal of
the Linnean Society 74: 351-364).
2.Commonly adaptive behavioral changes in response to drastic changes
uin environment or environmental stimuli precede evolutionary changes
in morphology. Evolutionary changes in behavior and morphology are
correlated.
The widespread idea that changes in behavior precede corresponding
evolutionary changes in morphology is reflected in a number of
aphorisms, such as "Behavior evolves first", "Behavior takes the lead
in evolution", etc.
Behaviors are the most plastic of all phenotypic characters hence
adaptive changes in behavior are first responses of the organisms to
stressful conditions of environment.
Behavior is not necessarily more plastic than anything else. In fact a
great many behaviors are quite evolutionarily conserved in major taxa.
That's an urban legend.

"There are reasons to believe that behavioral shifts have been
involved in most evolutionary innovations, hence the saying "behavior
is the pacemaker of evolution" (Mayr, E. 2001. What Evolution is.
Basic Books, p. 137)
All behaviors result from activity of particular neural circuits, from
processing of external/internal stimuli in neural circuits:
"Neural circuits are the basis of all behavior from simple reflex
withdrawal away from a noxious to a complex mating dance." (Delcomyn,
F. 1998. Foundations of Neurobiology. p. 602)
"Any behavior requires the functioning of a multicellular circuit
beginning with with input to the nervous system, propagation and the
interpretation of that input in the CNS, and output via neurons that
direct a response via neuromuscular, or neuroendocrine systems, or
both. Impairment of any part of such a circuit is likely to cause
decrements in the behavior it subserves." (Baker, B.S. et al. 2001.
Cell 105:13-24)
Most behaviors are motor behaviors, which are expression of "discrete
neural programs" (Gould, J.L. 1982. Ethology - The Mechanisms and
Evolution of Behavior. p.177).
I'm still waiting for anything to do with inheritance, which is the
important bit. None of this, so far, conflicts in any way with the
standard theory.

Supporting evidence
In experiments on functional mechanisms of predator-induced changes in
morphology and behavior of Hyla versicolor tadpoles, van Buskirk and
McCollum have observed that changes in behavior, on the one hand, and
the color and relative length and depth of tadpole body and tail, on
the other, vary as an integrated unit.
"Behaviour, colour and morphology are highly correlated in naturally
occurring tadpoles" (van Buskirk, J. and McCollum, S.A. 2000. Journal
of Evolutionary Biology 13: 336-347).
Fuchs et al. (2003) also have described the existence of a
relationship between the behavior and morphological and physiological
changes and have pointed out the role of behavior in inducing
physiological changes in the case of phase transition in locusts:
"Locusts are capable of extreme behavioral plasticity; in response to
changes in population density, they dramatically alter their behavior.
These changes in behavior facilitate the appearance of various
morphological and physiological changes, cumulatively termed density-
dependent phase characteristics... the behavioral changes are, on the
one hand, a response to specific environmental changes, and on the
other, stimulant-catalysts of various other environmentally induced
physiological changes." (Fuchs, E. et al., 2003. Journal of
Neurobiology 57: 152-162)
Observations on locust phase transition show that a single stimulus,
visual-social (crowding), olfactory (aggregation pheromone), or
tactile (touch on the outer side of the upper portion of a hind leg)
is both necessary and sufficient for stimulating impressive behavioral
and morphological changes of phase transition within a few to 24
hours.
Behaviour precedes colouration as an indicator of gregarious phase
transformation (Simpson, S.J. and Miller, G.A. 2007. Journal of Insect
Physiology 53: 869-876).
The fact that the circuitry for gregarious behavior and circuitries
for gregarious morphology in locusts are activated by the same
stimulus, suggest that at some level of the brain function or
structure, behavioral circuits are related to circuitries that, via
signal cascades, determine the development of gregarious morphologies.
The fact that behavioral change precedes the appearance of
morphological changes suggests that induction of the circuit for
changed behavior may somehow influence the circuit(s) determining
changes in the color and morphology, although the possibility of an
independent, parallel activation of the latter by the same stimuli
cannot be excluded.
The tadpole of the neotropical frog, Rana palmipes, responds to the
presence of its predator water bug, or even of its predator cues
alone, with behavioral changes (by strongly reducing its activity)
and, by darkening its body color and increasing the size of muscle and
tail (McIntyre, P.B. et al. 2004. Oecologia 141: 130-138).
In response to the presence of its predators, the freshwater snail,
Helisoma trivolis, simultaneously changes its behavior (preference for
a particular habitat and the timing of the onset of the reproductive
behavior) and morphology (the form of the shell) (Hoverman, J.T. et
al., 2005. Oecologia 144:481-491).
Acyrthosiphon pisum (Harris, 1776) is a pea aphid that in the presence
of predators emits a volatile alarm pheromone, which, when perceived
in the brain of females, induces the latter not only to shift to
walking behavior and drop off the plants but also to increase the
proportion of winged morphs in the offspring (Dixon, A.F.G. and
Agarwala, B.K. 1999. Proc Royal Soc London Series Biological Sciences
266:1549-1553; Kunert, G. and Weiser, W.W. 2003. Oecologia 135:
304-312).
North American frogs of the genus Scaphiopus are omnivorous amphibians
that, as tadpoles, inhabit ephemeral ponds and flooded areas, which
only exist for short periods of time, often before the tadpoles could
develop into adult terrestrial individuals. These species exhibit an
adaptive strategy, a developmental plasticity that enables a
proportion of tadpoles to develop an alternative carnivorous behavior
and mouth morphology. The carnivorous tadpole morphology is similar to
mouth adaptations of Hoplobatrachus tadpoles. Tadpoles of both groups
have longer intestines than those of other carnivorous species
(Grosjean, S. et al., 2004. Biological Journal of the Linnean Society
81: 171-181).
Larvae of the pipevine swallowtail butterfly, Battus philenor in
California in response to the higher summer temperature, exhibit a
double (behavioral and morphological) phenotypic plasticity. In order
to avoid the excessive summer heat, they switch to a new climbing
behavior by climbing higher on non-host plants and change their body
color from black to red. These changes are adaptive, for both color
change and climbing allow the larvae to escape the higher
temperatures. The critical temperature for the onset of the
polyphenism lies between 300C and 360C. Both the red color and
climbing behavior are components of a thermoregulatory strategy
intended to avoid internal temperatures above the thermal maximum
temperature for growth and development in B. philenor or to maintain
body temperatures in the optimum range for facilitating maximum growth
rate... (Nice, C.C. and Fordyce, J.A. 2006. Oecologia 146: 541-548).
How did any of these responses evolve?

All of the above are cases of developmental plasticity, i.e. are
epigenetic
phenomena not related to changes in genes (the same organism
produces three-four different morphs). This model explains how changes
in morphology evolve epigenetically without changes in genes.

No it doesn't. It explains how an evolved ability to respond to
environment can respond to environment. In a few cases the effects of
that response can be inherited for a few generations, though obviously a
longer inheritance would be selected against: the selected feature is
the ability to respond.

I know you believe that changes in genes are necessary
but investigators think differently. Why don't you rgue with them?

3. The neural circuit responsible for the development of the adaptive
morphology, starts a signal cascade inducing production of a maternal
factor that is deposited in the cytoplasm for inducing the development
of the same or a new trait in the offspring.
Supporting evidence
There is direct experimental evidence on the generation of adaptive
epigenetic information in the central nervous system and its
nongenetic transmission via gametes to the offspring.
Diapausing mothers of the flesh fly Sarcophaga bullata, which as
pupae are reared under a short photoperiod (SP), prevent the
"normal" appearance of this life history character in the offspring.
How do diapausing mothers generate and transfer information for
a new life history character and the associating changes in the
content of their eggs, without the "changes in genes or regulatory
sequences"?
Since the shortening of day length is perceived in mother's brain,
obviously, it is the mother that induces the new character in the
offspring.
"The information transfer from mother's brain (the site of the
photoperiodic reception) to her ovaries occurs sometime after
pupariation." Henrich, V.C. and Denlinger, D.L. 1982. Journal of
Insect Physiology 28: 881-884)
Investigators were able to suppress the appearance of diapause by the
administration of extracts from brains of SP mothers and/or
neurotransmitter GABA (gamma aminobutyric acid) (Webb, M-L. and
Denlinger, 1998 D.L. Physiological Entomology 23: 184-191; Denlinger,
D. L. 2002. Annual Review of Entomology 47: 93-122.). They also found
that a unique mRNA was present in the ovary of the SP mothers. Pupae
fail to break diapause if either the brain or the ring gland is
removed or if their nervous connections are severed. All the evidence
indicates that a still unknown maternal cytoplasmic factor deposited
in the egg cell is responsible for inducing the new character in the
offspring (Webb, M-L. and Denlinger, 1998. D.L. Physiological
Entomology 23: 184-191).
The epigenetic information for the new trait here is transmited to F1
but it does not persist in future generations.
I wonder how this response evolved.

The evolution of neural circuits doesn't need changes in genes.

So you say. I am still waiting for some evidence of this claim; any
evidence at all.

All my examples involve no changes in genes. You say No,
This reminds me Epurr' si muove.

4. The central nervous system controls production and spatial
arrangement of parental cytoplasmic factors in the oocyte
The ordered deposition of different maternal factors into the oocyte
cytoplasm requires expression (transcription and/or translation) of
thousands of strictly selected genes into respective long-standing
mRNAs or proteins their, their transport to oocytes and their
predetermined placement in specific regions of the oocyte. This is not
a random process but requires information of a non-genetic type (for
determining the order of amino acids in protein molecules). Let's
remember: what makes the egg uniquely capable of entering the process
of development is not the genetic information for protein
biosynthesis, which is the same in all the cells of the body, but the
epigenetic information in the form of strict spatial arrangement of
cytoplasmic factors in the egg.
Patterns of deposition of maternal factors in the oocyte are neurally
determined. They are deposited in a strictly determined order and
abnormalities in their spatial arrangement lead to abnormal
development or can disrupt the development. This spatial arrangement
of thousands of cytoplasmic factors represents the epigenetic
information that directs the whole process of early development,
including the development of the operational central nervous system
at the phylotypic stage.
Supporting evidence
Neural control of deposition of maternal factors in insect oocytes
In insects the deposition of maternal factors is made in two main
neurally determined ways:
Receptor-mediated endocytosis.
A "cephalic event" (Handler, A.M. and Postletwait, J.H. 1977. The
Journal of Experimental Zoology 202: 389-402) and two neurally-
controlled and -regulated hormones the juvenile hormone (JH) (Sorge,
D. et al. 2000. Journal of Insect Physiology 46: 969-976) and ecdysone
(Richard, D.S. et al. 2000. Intl. Conf. In honour of Prof D. Saunders,
Edinburgh (Abstract)) are essential for the endocytic uptake of
vitellogenin and other cytoplasmic factors (Chapman, R.F. 1998. The
Insects - Structure and Function. Fourth edition. p. 306) from
hemolymph by the oocyte.
Squeezing of nurse cell content into the oocyte
Most cytoplasmic factors in insect egg cells come from nurse cells via
squeezing of the content in a process that is neurally controlled via
maternal ecdysone. A common microtubule complex extends from the
posterior part of the oocyte to nurse cells, serving as a scaffold on
which mRNAs are orderly transported into the oocyte. This takes place
as part of nurse cell apoptosis that is also neurally regulated by
secretion in the insect brain of PTTH via ecdysone, which by
activating a caspase controls formation of actin bundles and the
squeezing of the nurse cell cytoplasm into the oocyte (Buszczak, M.
and Cooley, L. 2000. Cell Death and Differentiation 7: 1071-1074)
regulated. When the activity of ecdysone in nurse cells is
experimentally disrupted oogenesis is defective (Carney, G.E. and
Bender, M. 2000. Genetics 154: 1203-1211)
Neural control of placement of maternal factors in vertebrate oocytes
Modification of plasma hormone level
A neurally determined increasing pattern of the level of testosterone
during egg-laying in the canary (Serinus canaria) leads to the
progressive increase of testosterone in the yolk of consecutively laid
eggs. The fact that higher levels of testosterone increase the
viability of the developing bird and the mass of the hatching muscle,
suggests that this is an adaptive maternal investment that compensates
for the disadvantaged later-hatched nestlings.
"Here we have a mechanism which communicates environmental conditions
from the mother to the offspring, and this mechanism serves to
optimize reproduction and/or modify offspring traits. (Schwabl, H.
1996. Journal of Experimental Zoology 276: 157-163).
In response to various environmental stresses (presence of predators,
hunger, diseases, etc.) the Japanese quail (Coturnix coturnix
japonica) responds by neurally activating the hypothalamus-pituitary-
adrenal axis (corticotropin-releasing hormone → corticotropin-->
corticosterone), thus inducing a rise in the blood corticosterone
level, which is reflected in a proportional increase of the hormone
content in the egg yolk. The response is adaptive because it leads to
slower growth of hatchlings. (Hayward and Wingfield, 2004).
Differential uptake of maternal factors from the blood
The zebra finch, Taenopygia guttata, invests differentially in the egg
mass, proportionally to the attractiveness of the male mate and the
offspring varied in accordance with the differential investment:
"We have shown that the father's attractiveness, via maternal effects,
influences several aspects of offspring development. Furthermore, by
manipulating male attractiveness, randomly assigning breeding pairs,
cross-fostering clutches and using GLMs (general linear models) to
account for variance of other factors, we have eliminated any genetic
effects of the male and these effects must be mediated by egg
resources allocated differentially by the female." (Gilbert, L. et
al., 2006. Proc. Royal Soc. B: Biological Sciences 273: 1765-1771)
Besides parental cytoplasmic factors, possible adaptive changes in
other epigenetic structures such as centrioles, centrosomes and
related microtubular and cytoskeletal structures might be considerd
but I am not aware of relevant empirical evidence.
For further information on the neural control of deposition of
maternal factors in the oocyte see my Epigenetic Principles of
Evolution or visit my website
http://www.epigeneticscomesofage.com
That's mighty thin evidence for the claim of thousands of factors,
ever-so-carefully placed and organized. Most of it refers just to
increases in concentration of various simple substances in the yolk, or
even mere increases in size of the yolk. This is hardly the sort of
thing that can carry vast amounts of information between generations. At
most, what you have here are arbitrary triggers whose action depends
critically on the genetics of the zygotes that receive those triggers.

Most of cytoplasmic factors in the oocyte are localized in specific
parts of the oocyte. They do not know how or why they have to go
there. Genes don't know eitherl. They are transported there via
microtubules. These dynamic structures change their form and length
(polymerize/depolymerize) under the action of numerous hormones that
are under the ultimate neural control.

This claim has so far not been supported. While "yolk" may be a
specific part of the oocyte, it's hardly a pinpoint designation
capable of> storing more complexity than the genome.

What about the bicoid, Vasa, cyclins and the bulk of epigenetic
information in the egg cell. Are not theytransported to their specific
locations via microtubules and are not these microtubules
regulated by hormones and are not these hormones regulated
by the nervous system? Do you know of any gene determining the
distribution of the epigenetic information in the egg cell?

5. The operational CNS at the phylotypic stage develops from the
epigenetic information (orderly arranged maternal/paternal cytoplasmic
factors in gametes).
Supporting evidence
The early development is controlled by cytoplasmic factors (epigenetic
information) parentally deposited in the egg cell (Wolpert et al.,
1998. Principles of Development. pp.63-70 and 127-146; Hall, B.K.
1998. Evolutionary Developmental Biology. Sec edition. pp. 114-119;
Gilbert, S.F. 2000. Developmental Biology. Sixth edition, p. 223) and
so is the development of the operational central nervous system at the
phylotypic stage and more than 30 years ago, in 1987, Pieter D.
Nieuwkoop concluded :
"Embryonic
induction is clearly an epigenetic process
" and so is the whole vertebrate development (1987. The epigenetic
nature of vertebrate development: an interview of
Pieter D. Nieuwkoop on the occasion of his 70th birthday
NieuwkoopDevelopment 101. 653-657 (1987)
This has nothing to do with your claim. Of course development is an
epigenetic process. That's never been at issue. Here's are the
questions: 1) What causes differences in development between species?
and 2) How are those differences inherited? So far, we have nothing on
either.

O.K. John. Now that you admit that "development is an
epigenetic process" rather than a genetic process we
are closer than ever before.

Please. You misunderstand.

Can't you tell me what did I misunderstand?

You call the development
an epigenetic process not because genes are not involved
in the development (genes are indispensable for the
development of the egg/zygote into an adult organism).
You call the development an epigenetic process for another
reason, because the expression of genes and cell
differentiation is epigenetically determined during the
early development by parentally provided epigenetic
information (parentally provided cytoplasmic factors
and epigenetic structures such as centrioles/centrosomes,
and related microtubular structures and the cytoskeleton).
Right?

Wrong. I call it epigenetic because it involves complex regulatory
networks and feedback between the genome and the environment, i.e. the
immediate surroundings of cells, diffusing substances, etc.

I don't understand, even if it was a lapsus, is development
an epigenetic or a genetic process? I need to understand do
you believe in a genetic program that unfolds in the process
of individual development?
Yes or no?

Next step is to ask what causes changes in these networks. Now it should
be obvious that if networks consist of chains of stimuli and receivers,
one can alter the process by changing either of those. Note that the
genome is the nearly universal receiver here. Thus you can change
development by changing the genome.

Without evidence all that is empty rhetoric.

Given that a change in morphology, in the simplest
case, is ultimately a change in the number and
spatial arrangement of cells of particular types any
change in morphology is epigenetically determined.

Yes. Now what heritable changes result in changes in the epigenetic
processes of development? Changes to the genome, of course.

No. No one has ever demonstrated that a change in genome has led
to a particular evolutionary change in metazoans (although
I don't exclude this as a rare theoretical possibility). Not
hypothetical changes in the genome but changes in the
epigenetic information generated by the parental CNS(s) and
deposited in gametes (in placentals also transplacental) are
source of evolutionary changes.
In cases of evolutionary changes the offspring CNS
inherits the ability to generate the same epigenetic
information and deposit it in the egg/gamete.

In the cases of transgenerational plasticity and in the
cases of evolutionary changes, I have presented signals
for these changes that are of epigenetic origin: they come
from the central nervous system. Let's remember, the
expression of genes in the CNS typically takes place
in a nonclassical way as it occurs in the rest of the body;
it is the result of a processing of various internal and external
stimuli.

You have presented no such evidence. You have in some cases shown
evidence that Y is caused by X. But what causes X? W? What causes W? V?
My claim is that evolutionary changes in development can all be traced
back to genetic changes. You have presented no evidence for any other cause.

Let me remind just one fresh example: the loss of forelimbs in
pythons.
All the genes involved in limb development are present. No evidence
of
any changes in regulatory sequences and above all the same genes
function in hind limbs but don't function in the forelimbs. This fact
alone
absolutely excludes any change in genes or regulatory seqyence as
cause of the loss of forelimbs. The change cannot be "traced back
genetic changes" but to a change in the chemical behavior of the
embryonic CNS (explained in this same thread a couple of hours
ago).

6. The new maternal/paternal cytoplasmic factor(s) represents a
change in the zygotic epigenetic information, which induces a change
in the structure/function of the phylotypic central nervous system.
The newly inherited structure is a source of new afferent input to the
central nervous system, in response to which the central nervous
system modifies the existing neural circuits or establishes a new
neural circuit. Changes in the structure of neural circuits change
their computational properties.
What does "new" mean above?

In the process of embryonic development the information on the
developing embryo structures is transmittted and received in the
CNS as a stimulus.

You have presented no evidence that this is any different from the
interactions among other tissue types that result in harmonious
development. You have presented no evidence that this is a mechanism for
inheritance of evolutionary changes.

i have presented adequate evidence that changes in the developing
structure of embryo are reflected in the structure of neural
circuits
and that prevention of the afferent input prevents normal formation
of neural circuits in the CNS which are responsible for starting
almost all signal cascades for expression of non-housekeeping genes.

Supporting evidence that the new structure may lead to changes in the
structure of neural circuits or their computational properties
From the phylotypic stage on, a continuous input of internal stimuli
(changes in the developing embryonic structure) via afferents, is
communicated to the CNS. The embryonic CNS responds to that input by
"spontaneous" electrical activity, which determines the wiring and the
establishment of neural circuits in the brain (Peinado, A. 2000Journal
of Neuroscience 20: 1-6; Zhang, L.I. and Poo, M. 2001. Nature
Neuroscience Suppl. 4: 1207-1214). In retina, e.g. this activity "can
produce highly stereotyped patterns of connections before the onset of
visual experience" (Penn et al. 1998), and instruct formation of eye-
specific layers (Shatz, C. 1996. Proceedings of the National Academy
of Sciences USA 93: 602-608). By contrast, in the absence of afferent
input normal neural circuits are not formed (Penn et al. 1998) and rat
striatal neurons do not develop dendritic spines (Sega, M. et al.
2003.European 17: 2573-2585Journal of Neuroscience ).
The fact that in response to the input of afferent stimuli (changes in
the developing embryonic structure) neural circuits modify their
synaptic morphology suggests that synaptic connections may somehow be
related to the developing embryonic structure. Indeed, experimental
delay of muscle development causes suspension of synaptic branching of
respective motoneurons (Fernandez, J.J. and Keshishian, H. 1998.
Development 125: 1769-1779); male rats castrated on day 1 have
significantly reduced numbers of shaft and spine synapses in the
ventro-lateral part of the VMH (Matsumoto, A. and Arai, Y. 1986.
Neuroendocrinology 42: 232-236), and ovariectomy causes a profound
decrease in the dendritic spine density of pyramidal cells of the
hippocampus. In D. melanogaster, where the larva lacks the target
muscle (no input of stimuli) the axon of the motoneuron MN5 develops
no dendritic connections (Consoulas, C. et al. 2002. Journal of
Neuroscience 22: 4906-4917). In experiments with the moth, Manduca
secta, the input of stimuli from the adult leg is involved in shaping
the growth of motoneuron dendrites (Kent, K.S. and Levine, R.B. 1993.
Journal of Neurobiology 24: 1-22).
In other experiments it has been shown that the spontaneous activity
arising in response to the input of stimuli (changes in the embryonic
structure) is necessary for further development of that structure. So,
e.g., suppression of the spontaneous activity by paralysing
motoneurons in chick embryos (Hal, B.K.l and Herring, S.W. 1990.
Journal of Morphology 206: 45-56) and duck embryos (Creazzo, T.L. and
Sohal, G.S. 1983. Cell and Tissue Research 228: 1-12) results in the
reduction of the bone- and muscle growth, while denervation totally
prevents the development of muscles in duck embryos (Sohal and Holt
1980; Creazzo, T.L. and Sohal, G.S. 1983. Ibidem) and Drosophila
(Enard et al. 2002). It has also been shown that "Many developing
networks exhibit a transient period of spontaneous activity that is
believed to be important developmentally." and in the spinal cord
spontaneous activity, is "implicated in the development of limb
muscles, bones and joints." (Wenner. P. and O'Donovan, M.J. 2001.
Journal of Neurophysiology 86: 1481-1498)
If I can understand your opaque verbiage, this seems to be a claim that
the nervous system and the rest of the body get rich by taking in each
other's washing. Morphology induces CNS, and CNS induces morphology, and
it all starts from a few simple parental factors, which are deposited as
a result of the particular neural structures they in turn result in. But
you really have presented no evidence that such a chain of causation
actually exists. Instead what you have shown is that various developing
organs adapt to other developing organs; nerves and blood vessels grow
to innervate and nourish tissues, even if those tissues expand, without
the need for special mutations affecting their development. That's
because of an evolved feedback system among tissues. It's not an engine
of evolution.

I suspect you need to read it once again or, for more information,
go to chapter 2 of my book.

You need to back up your claims.

6. In the process of reproduction the new/modified neural circuit,
whose computational properties have appropriately changed, can start
the same cascade that the parental circuit used for production and
deposition of the new cytoplasmic factor even in the absence of the
environmental stimulus. This is what occurs in cases of
transgenerational developmental plasticity in Daphnia magna,
Schistocerca gregaria, Brachionus angularis, etc. do.
Although we will never be able to directly prove the ways in which
particular evolutionary events took place millions of years ago we
have at least two other ways to reasonably deal with the issue:
Actually, we have many ways to "directly prove" (really bad scientific
terminology there) such things. We can compare related species in the
context of a phylogenetic tree. Using that, we can tell much about what
changed and when.

That also is not "direct".

You're starting to sound like a creationist here: "Were you there?" Your
understanding of scientific methodology is flawed. Historical sciences
are sciences.

I will not be engaged in empty and distracting ideological arguments.

1.Cases of transgenerational developmental plasticity are known when
new characters are transmitted to the offspring and persist for
varying number of generations
But never enough to be evolutionarily important, right?

Yes. But they show us that metazoans have
evolved epigenetic mechanisms to change their
morphology without changing genes. It is hard
to believe that having evolved this precious ability
metazoans wouild lose it. Evolution does not work
that way. Right?

Well, they would lose it if it were no longer advantageous in whatever
environment they're currently in. My point, however, is that the action
of this evolved response is not evolution. The evolution of the ability
to respond in some particular way is evolution, but you have
specifically disclaimed interest in that. You are left with using
non-evolution as your evidence of evolution. Not a good idea.

Excellent evolutionary idea: advantageous achievement of
evolution will be lost. Why? Becase your genecentrist model
need them to be lost?

2.The relevant changes (both epigenetic and epigenetic) that occurred
in the past, or their consequences, have to be present in modern
organisms if the evolutionary change is not to be lost.
Certainly true if we want to look at something that isn't preserved in
fossils, which is of course the great majority of features.

Supporting evidence
Let's first consider a few cases of transgenerational developmental
plasticity,
where an epigenetically determined change in mother's brain via
gametes induces in the offspring a morphological change that persists
for several generations.
Why? The inheritance isn't stable enough to be evolutionarily
meaningful. Besides, what caused this epigenetic response to evolve?
That's the real question.

Adaptation is an inherent property of living organisms.

Non-responsive. You are conflating two senses of the word. Adaptation as
an inherent property of organisms consists of natural selection acting
on the genome. Adaptation as a plastic response to changes in
environment without genetic change is not universal; it's a set of very
specific evolved abilities that differ radically from group to group.
The latter are not evolution, though the gain of such responses is
evolution. You, however, have disclaimed all interest in the evolution
of responses. Of course that evolution involves genetic changes.

Trying to make a strawman again? I did not say that these responses
are
evolutionary changes but they show us that metazoans have evolved
mechanisms of transmission to the offspring of new characters
without
changes in genes. And this is very important from an evolutionary
point of view. And the role of developmental plasticity in evolution
is
accepted by many leaders of the modern biological thought (M.J. West-
Eberhard,
Nijhout, Schlichting, Piggliucci, etc.).

In an adaptive response to a social stimulus, such as crowding, and
the shortening of photoperiod, Daphnia magna, an all-female species,
produces sexually reproducing generation (male and female individuals)
with respective changes in the structure of eggs.
This transition is also experimentally induced by exposing maturing
oocytes to this species' juvenoid hormone, methyl farnesoate, and
even to its analogs. The signal cascade leading to such a sudden and
radical transition is as follows:
Environmental stimuli → Sensory organs (exteroceptors/interoceptors)
→
Processing in the central nervous system of electrical signals into
which stimuli are converted → Secretion of MOIH (mandibular organ-
inhibiting) neurohormones secreted by neurons of the X organ →
Secretion of methyl farnesoate by the mandibular organ → Egg cell.
Another cyclically parthenogenetic rotifer, Brachionus angularis,
in response to crowding and a kairomone released by conspecifics,
gives birth to haploid eggs developing into males that, when
fertilized develop into diapausing eggs, which hatch into female
individuals incapable of sexual reproduction for several generations.
Here is the investigator's interpretation of
the mechanism of the epigenetic inheritance:
"The proposed chemical responsible for the crowding stimulus could
diffuse into the maternal body cavity and directly affect the oocyte
such that the mictic-female phenotype is expressed later on in
development....Alternatively, the chemical could directly affect the
physiology of the mother. For example, it could target the nervous
system via chemoreceptors, and some secreted factor could then affect
the growing oocyte (Gilbert, J.J. 2003. Evolution & Development 5:
19-24).
Another rotifer, Brachionus calycifloris, when detects the presence
of
its predator, produces offspring with an additional pair of
spines, which protect them from being eaten by the predator and the
new character is also transmitted for many generations.
"The stressed locusts transmit the acquired traits to the offspring.
The full scale phase transformation takes several generations and
occurs probably only in nature (Pener, M.P. et al., 1997. Comparative
Biochemistry and Physiology B 117:513-524).
Phase transition in Schistocerca gregaria is associated by
transmission of a number of changed morphological, physiological, and
behavioral characters to the offspring.
"This process is epigenetic, being transgenerational, inducible and
persistent for some duration in the absence of inducing
stimuli." [Jablonka and Lamb, 2002; Jablonka and Lamb, 2005; Jablonka
et al., 2002 (according to Miller, G.A. et al. 2008. Journal of
Experimental Biology 211: 370-376)]
All the phase change-inducing factors act via the insect central
nervous system [crowding in this insect is a stressor that also acts
via the CNS as is concluded by the experimental evidence that
antennectomized locusts do not change phase under conditions of
crowding (Applebaum and Heifetz, 1999)].
The transfer of phase state across generations in locusts is clearly
epigenetic (Simpson, S.J. and Miller, G.A. 2007. Journal of Insect
Physiology 53: 869-876)
"Epigenetic transfer of phase state depends upon low molecular
mass, water-soluble chemicals within foam secreted by the
reproductive accessory glands at the time of oviposition...a specific
chemical agent responsible for transmission of gregarious behaviour
between locust generations." ( Miller, G.A. et al. 2008. Journal of
Experimental Biology 211: 370-376) "and perhaps also from what appears
to be identical glandular tissue lining the oviduct. Exposure to
this material soon after ovulation, in the oviduct fluid and/
or in the egg foam after oviposition, results in the graded
development of gregarious behaviour and colouration in
the resulting hatchlings. " (Simpson, S.J. and Miller, G.A. 2007.
Ibidem)
Intense changes are observed in the levels of numerous
neurotransmitters in the locust brain (Rogers, S.M. et al., 2004. The
Journal of Experimental Biology 207:3603-3617). At a neuroendocrine
level this transformation is related to an elevated level of JH
(juvenile hormone) under stimulation of neurohormones allatotropins
and nerves innervating the corpora allata as well as cerebral
secretion of [His7]-corazonin (Grach, C. et al., 2003. Journal of
Peptide Research 62: 135-142), also known as DCIN (dark-color-inducing
neurohormone). A 5-10-fold increase of the amount of a cytoplasmic
factor, the neurally regulated ecdysteroid hormones was found in the
eggs of gregarious locusts, than in the eggs of the solitarious
locusts (Tawfik, A. I. et al., 1999. Proceedings of the National
Academy of Sciences USA 96:7083-7087; Tawfik, A.I. and Sehnal, F.
2003. Physiological Entomology 28: 19-24; Hagele, B.F. et al. 2004.
Journal of Insect Physiology 50: 621-628 ).
Loss of Forelimbs in Pythons
Pythons have no forelimbs but they develop reduced hind limbs. The
loss of forelimbs in pythons is believed to only be related to an
anterior
expansion of expression pattern of Hox genes (not any mutation in the
gene or its regulatory sequences):
Hold on there. Who says that changes in expression patterns have nothing
to do with regulatory sequences?

Argumentum ex silentio, among other things. Do you know of any change
in regulatory sequences in pythons related to the loss of their limbs?
Investigators don't and even don't allude to it.

Yes they do. The very paper you cite for this says (last paragraph):
""Such higher-order *genetic* changes could have resulted in sudden
anatomical transformations, rather than gradual changes, during snake
evolution, a hypothesis which can be tested by the fossil record."

That paper contains no discussion of the genetic mechanism, but the
authors clearly have no doubt that the mechanism is genetic. They may be
wrong, but my point is that this paper is not evidence that the
mechanism is non-genetic. You consistently confuse proximate cause with
ultimate cause.

We are fed with hypotheses. What you need is empirical evidence which
you
have long failing to find (it is not your fault for that evidence is
not there)


"Progressive expansion of Hox gene expression domains along the body
axis can account for the major morphological transitions in snake
evolution." (Cohn, M.J. and Tickle, C. 1999. Nature 399: 474-479)
Pythons have no forelimbs but develop hind limb buds and rudimentary
hind limbs with truncated pelvic girdle and femur. However, they are
unable to express Shh because they have no AER (apical ectodermal
ridge) and they do not express in their ectoderm AER-related genes:
Dlx (Distal-less), Fgf2
and Msx (Cohn and Tickle, 1999, Ibidem), while these genes are
normally expressed in other organs of the python embryo (Cohn and
Tickle, 1999 Ibidem).
Exactly. This is standard evo-devo. Snakes have a different
tissue-specific expression pattern for some gene or genes upstream of
the limb development. This differences is probably due to loss of a
transcription factor binding site in the promoter of that gene, a
binding site for some gene product just a bit farther upstream. While I
can't point to the particular genetic change, neither can you claim it
doesn't exist on the basis of this paper. What you're claiming here,
whether you realize it or not, is that expression patterns have nothing
to do with transcription factor binding sites.

Enough with "probably". No evidence - no valid argument.

I merely point out that the existence of a regulatory difference is not
evidence that the difference is non-genetic.

But you have no evidence of that difference.

That's how you were using the paper, and that use is invalid.

You have absoultely no ground for assuming that such a change
might have occurred. The Hox gene and its regulatory
sequence is unchanged and functiona. It is the same in
all the cells of the body but it works in the hind limbs bot
does not in the fore limbs. This absolutely excludes any
change in the gene or its regulatory sequence as cause
of the loss of limbs in pythons. Besides, I have a mechanism
of neural regulation of expression of the Hox gene which
explains how the expression in the fore limb is prevented.


Since the cause of the loss of forelimbs in pythons is an anterior
expression of Hox genes and expression of these genes along the body
axis is negatively regulated by RA in which the neural tube and motor
neurons has been shown to play the crucial role (forelimbs and
hindlimbs in tetrapods develop where the neurally secreted RA is
higher and consequently, where expression of Hox genes is suppressed).
That's not a sentence. Since....then what?

The cause of the loss of forelimbs is a signal from the CNS and motor
neurons via RA.

I saw no such claim in the paper in question. My copy is missing a page,
so perhaps you can find such a claim on that page. But where and what is
it? Note also that regulation has two sides: signal and receiver. A
change in regulation is not grounds to assume that the signal has
changed; the receiver might have changed. How have you resolved this
ambiguity?

If your receiver is the Hox gene or its regularory sequence its
change is by common sense excluded for the reasons I have
just explained

Evolution of paedomorphosis in salamanders
Metamorphosis in salamanders is stimulated by a surge in the level of
the hormone thyroxine determined by a signal cascade that starts in
the salamander's brain: (neurons of the hypothalamic paraventricular
nucleus secrete TRH (thyrotropic releasing hormone)→ neurons of the
pituitary secrete TSH (thyroid stimulating hormone) → Thyroid gland
secretes T4 + T3 → thyroid hormones bind their nuclear receptors,
thus
starting metamorphosis processes (fin elimination, skin changes,
etc.).
The timing of the activation of the cascade is determined by the
"hypothalamic maturation comprising neurons of several regulatory
centers and culminating at the time of the secretory
surge." (Rosenkilde, P. and Ussing, A.P.1996. International Journal
of Developmental Biology 40: 665-673).
Paedomorphic salamanders fail to generate the characteristic burst of
hypothalamic stimulation for activating the thyroid axis. This is
considered
to be the main mechanism behind the axolotl paedomorphosis (Rosenkilde
and Ussing, 1996. Ibidem).
Metamorphosis has been experimentally induced in paedomorphic
salamanders by administration of thyroid hormones but also by
stressful conditions (capture stress and conditions of captivity),
which cause general disturbance in the central nervous system
(Rosenkilde and Ussing, 1996, Ibidem).
Conversion of paedomorphic salamanders into metamorphosizing
salamanders under stress conditions and cases of spontaneous
metamorphosis in paedomorphic salamanders unambiguously demonstrate
that evolutionary transition to paedomorphosis involved no changes in
functions of relevant genes or their regulatory sequences.
It is believed that the cause of the interruption of the
metamorphosis-
inducing cascade is that neurons in hypothalamus have adaptively
heightened the setpoint for responding to low levels premetamorphic
levels of thyroxine that stimulates activation of the cascade in
metamorphosizing salamanders. Changes in set points are a well known
epigenetic function of hypothalamus in vertebrates.
What causes a change in setpoint? How are those changes inherited?

For the first question read 4 lines above and for the second
remember that by admitting that the development is an epigenetic
(not genetic) process you have found the right answer: it is
epigenetically inherited via the mechanism I describe in my model.

All I see is that the hypothalamus changes the set point. What causes
the hypothalamus to change the set point? How is this change inherited?
Don't say "epigenetically". Tell me the detailed mechanism by which
inheritance happens. You already have my mechanism of inheritance:
replication of genomes, a process that is quite detailed and well
understood. All you seem to have is a single word.

You have nothing related to a change in a set point. Set points are
determined in the hypothaslamus and they are computationallly
determined. I have evidence that set points are determined in the
hypothalamus;you have not evidence that any gene or group of genes are
responsible for determining set points (it takes a lot of
"intelligence" to do that).

A tremendous difficulty for any theory of evolutionary change is
identifification of the mechanism that would enable the organism to
restrict the use of the new information at the site of the
evolutionary change.
I don't understand that sentence. Do you mean to ask what causes
tissue-specific changes in expression patterns? If so, the answer isn't
really a problem. It's mutations that alter regulatory networks. The
most common case is what I've been saying all along: modification of the
sequences of transcription factor binding sites in upstream promoters.

That makes no sense to me. These hypothetical modifications will be
the same in all cells of the body.

Yes, but they won't act in all cells. A new, deleted, or altered
transcription factor binding site will have a phenotypic effect only in
those cells in which that transcription factor is expressed. You are
exposing your profound lack of understanding of gene regulation and
regulatory networks. Again, I suggest you read one or more of Sean
Carroll's books. They present a basic understanding of these concepts,
essential if you are to carry on any meaningful conversation on development.

Empty words. No substance. No evidence. I have provided you a
mechanism of differential expression of genes in different tissues
and cells which derives from experimental evidence. Can you present
your evidence. I doubt.

We know that in many cases this is made by
shutting off the respective receptor of the inducer in all the cells
except those that will develop into new structure. According to this
epigenetic theory of evolutionary change:
That's not an epigenetic theory of evolutionary change. It's an
epigenetic theory of development. We all agree that development is
controlled by regulatory networks. Now: what causes
evolutionary/heritable changes in regulatory networks?

I have shown you, in numerous examples, that changes in
regulatory networks and the CNS of the offspring are induced
by signals from the parental central nervous system.

Actually, I don't recall any example of that. You have shown some cases
in which parental transcripts are deposited in the ovum under CNS
stimulus. You have shown that these transcripts have developmental
effects. But I don't recall anything that carried the chain through to
causing the development of a system that would deposit identical
parental transcripts in the next generation of ova. Refresh my memory.
Briefly.

It is my pleasure: The signal cascade of transgeneratrional change in
D. magna, signal cascade of phase transition in S.gregaria, but a
very complex gene regulatory network activated by the the epigenetic
information is the regulation of the embryonic endomesoderm gene
regulatory network in Strongylocentrotus purpuratus described by
Davidson et al, 2003 (easy accessible in my website chapter 5 of my
book).

And none of the heritable differences you have mentioned are
evolutionary; they're all short-lived responses to environment,
resulting from evolved mechanisms of response. The response isn't
evolution; the mechanism arose by evolution, but you aren't talking
about that.

If that is an example iof transgenerational plasticity I have never
claimed
they are more than transitional transgenerational states with
potential
evolutionary consequences (so believe some distinguished biologists)

"Metazoans resolved the problem of selective restriction of the
hormone action to particular parts of the animal body at particular
times by evolving a binary, humoral and adjacent, control of gene
expression. In this control system the action of centrally induced
signal cascades is permitted or prevented by the action of local nerve
endings, which induce expression of specific hormone receptors only in
target regions of the body.
The activity of this binary system of gene expression is demonstrated
in well-established examples of myogenesis (Lawrence and Johnston,
1986; Currie and Bate, 1995; Bayline et al., 1998), osteogenesis
(Goss, R.J. 1969h; Zeng et al., 1996; Edoff et al., 1997; Demulder et
al., 1998), regeneration (Goss, R.J. 1969h; Hall, B.K., 1998k),
puberty in mammals (Riboni et al., 1998), oogenesis in vertebrates
(Morales et al., 1998), expression of receptors for pituitary LH
(luteinizing hormone) in testicles (Lee et al., 2002), regulation of
progesterone synthesis and reproductive physiology in humans (Fritz et
al., 2001), secretion of estrogen and progesterone under influence of
nervous fibers descending from the hypothalamus to the spinal cord, as
well as sympathetic and vagal preganglionic neurons (De Bortoli et
al., 1998), secretion of the juvenile hormone by corpora allata in
insects (Stay et al., 1996; Kou and Chen, 2000), ovulation and
determination of the number of deposited eggs in insects (Antkowiak
and Chase, 2003), regulation of ecdysone synthesis by the neurohormone
PTTH (prothoracicotropic hormone) and by direct neural control
(Chapman, 1998d), the development of the laryngeal muscle in male
Xenopus (Tobias et al., 1993), etc. "
(Cabej, N. 2008. Epigenetic Principles of Evolution. pp. 211-22)
You're quoting yourself. How charmingly self-important. And I see you've
gone back to incomplete citations. I don't think you have evidence for
this claim. Many of your complete citations, when followed, haven't said
what you claimed they did. You seem to believe that the existence of a
developmental explanation, i.e. a change in expression pattern, proves
that the change didn't result from genetically inherited mutations.

You are still speaking about "genetically inherited mutations" after
the long failure to find a single example of a mutation related to a
change in morphology?

Many such examples have been presented to you. You find a way to reject
all of them. You have never presented an example of an evolutionary
change due to epigenetic inheritance.

You are kidding.You have presented such mutations that led to
evolutionary changes in metazoans? Absolutely no relevant example.

No change in genes or sequences of their regulatory regions have been
identified in the examples of evolutionary changes I have presented in
previous posts (evolution of caste polymorphism in social insects,
loss of teeth in birds, loss of eyes in A. mexicanus, loss of
pigmentation in A. mexicanus, etc. ). But in all of them the
essential involvement of the central nervous system has been
demonstrated.
How are these changes inherited? What causes the evolutionary
differences among species? Has this question been answered for any of
the examples you give?

Yes.

No. If you disagree, give one example here.


Caste polymorphism in Pheidole ants: the maternal JH determines
formation of queens and workers. Later centrally determined JH pulses/
lack of pulses in specific switching points lead to formation workers
and soldiers. The queen repeats the same pattern of three JH switch
points.

Has an absence of changes in genes or sequences
been demonstrated?

John, Do you know what the burden of proof is?
Your logic is funny indeed. You make an assertion that
changes in genes change the morphology and then you
tell me to "Demonstrate to me that this change did not occur".
You have to prove your assertion not require others to
disprove it. By the same token a creationist would tell me:
"God created life on Earth, hence you have to
demonstrate to me that he did not."

You have to demonstrate that your claim is better than my claim. You
have to show that an evolutionary difference is due to a change in some
epigenetically inherited factor. You have presented no examples of this.
Instead we get a few short-lived examples of evolved stress responses --
not the mechanisms but their results -- and a list of developmental
changes that you merely assume are non-genetic. How about presenting
some evidence for your central claim?

I don't understand. Are you still insisting that I will demonstrate
you that
your assumed changes did not occur or you understand your request
is absurd? What would you say if I would ask you to prove me that my
mechanism does not work?

If this was supposed to be the post where you explained and supported
your central claim, it didn't do that. You haven't answered the basic
questions, nor have you explained why standard evo-devo is wrong.

II will not comment on your conclusions. I just tried to compare your
genetic model of evolutionary change with my epigenetic model.
I did my best I could here in TO to support my model with empirical
evidence but you did not even try to present some evidence.
I think this was the best you also could do: there is no evidence.

No, I'm just lazy. I don't look for these things unless I really have
to. But here's the first thing I found in few minutes' search:

N. Gompel, B. Prud'homme, P. J. Wittkopp, V. A. Kassner, & S. B.
Carroll. 2005. Chance caught on the wing: cis-regulatory evolution and
the origin of pigment patterns in Drosophila. Nature 433:481-487.

Abstract

The gain, loss or modification of morphological traits is generally
associated with changes in gene regulation during development. However,
the molecular bases underlying these evolutionary changes have remained
elusive. Here we identify one of the molecular mechanisms that
contributes to the evolutionary gain of a male-specific wing
pigmentation spot in Drosophila biarmipes, a species closely related to
Drosophila melanogaster. We show that the evolution of this spot
involved modifications of an ancestral cis-regulatory element of the
yellow pigmentation gene. This element has gained multiple binding sites
for transcription factors that are deeply conserved components of the
regulatory landscape controlling wing development, including the
selector protein Engrailed. The evolutionary stability of components of
regulatory landscapes, which can be co-opted by chance mutations in
cis-regulatory elements, might explain the repeated evolution of similar
morphological patterns, such as wing pigmentation patterns in flies.

Now I'm sure you will find something wrong with this, just as you've
managed to reject every bit of evidence anyone has found before. That's
the way you work. But it's certainly better evidence than anything you
have presented, in that it directly shows exactly what I'm claiming,
rather than being irrelevant.

John, this is indeed an experimentally verified case of a change in a
regulatory sequence of a gene that changed the wing pigmentation in a
Drosophila species. What you have to keep in mind, however, are the
following:
First and above all this is a change in expression of a gene whose
product is responsible for synthesis of melanin from its precursors,
not a changes in morphology as we have repeatedly defined here in TO
(a change in the number and spatial arrangement of cells of different
types).
Second, I have always pointed out in this discussion group that most
the biochemical evolution, i. e. of molecular evolution, in
unicellulars and multicellulars is product of gene mutations.
Third, I would not be surprised (this I have pointed out earlier even
in this thread) that some gene mutation
may be involved in morphological changes, but these occurrences are so
rare that cannot explain the enormous morphological evolution of
extant and extinct forms of life.
The fact that you and others here in TO are struggling to find
relevant examples of changes in genes that have led to particular
evolutionary changes in morphology is indicative of that.

Regards,

N.C.


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