A major advance in our understanding of heredity and genetics is recognizing that organism characters are produced by networks and not by individual "gene products." The idea of single-gene determination of phenotypic traits has yielded to systems biology.
As my friend Adam Wilkins expressed it writing about the features of multicellular organisms: "A mutation that affects a developmental process does so by affecting either a gene whose product acts as an upstream controlling element, an intermediary connecting link, or as a downstream output of the network that governs the trait's development." Multimolecular networks carry out every kind of vital activity. These include metabolism, biosynthesis, damage repair, sensing, signaling, cell division, cell differentiation, tissue formation and multicellular development.
In the early days of molecular biology, theorists like Francis Crick imagined that we could have a cellular division of labor where certain kinds of molecules (nucleic acids or DNA and RNA) provided the information and encoded the proteins, which did all the work. This was the basic idea behind his famous "Central Dogma of Molecular Biology" and underlies genetic determinism, the philosophy that "your genes are your destiny."
We now have a more sophisticated view and realize that cell networks involve different interacting molecular partners: proteins, DNA, RNA and many other biochemical classes. These partners fit together, modify each other's shapes (and sometimes even chemical composition), and combine to build higher-order structural complexes. Think of it as molecular Legos.
All the interactions between the various components determine what job each network does and how it processes regulatory information essential to making the task come out right for survival, growth and reproduction. It is a form of molecular circuitry, analogous to electronics, where different pieces are put together in defined arrangements for specific tasks.
Each functional network has its own architecture. The components are usually encoded by many different parts of the genome, and some of them are often particular DNA sequences located at different places. In order to execute most vital processes, for instance, dozens of proteins have to locate hundreds of discrete sites in the genome to produce the various molecules needed.
Switching from gene-based to network-based thinking raises many questions about how complex interactive networks change in the course of evolution. We know that certain types of networks have been copied and reused in modified form to take on new tasks in the course of evolution. Multicellular organisms emerged with organized body plans that have become increasingly complicated. Orchids have proliferated countless exotic and beautiful flowers. An eye development network has been adapted to control wing patterns in butterflies.
How do genomes encoding complex networks evolve to provide novel functions in any reasonable period of time? According to the conventional view of evolution as a random succession of independent, localized, slight changes, each providing its own selective advantage, the evolutionary process appears hopelessly slow and subject to taking too many steps backwards before it takes one forward.
The ideal solution would be rapid ways of copying and modifying the DNA encoding the network components on a wholesale basis. Although such processes were ruled out a priori by the founders of conventional evolutionary theory, they are just what molecular biologists studying DNA change and genome sequences have discovered: duplication and natural genetic engineering processes for amplifying and distributing DNA encoding network components throughout the genome.
In other words, natural genetic engineering is a way to build molecular circuits, Lego-like, rapidly. Let us see how this works and some of what has been documented so far.
The first step is often, but not always, duplication of the entire genome. This is one of the evolutionary benefits of sexual reproduction because rare couplings, either within a species or between different species, produce individuals that have undergone whole genome doubling (WGD). WGD has been documented in yeasts, other fungi, protists, and even vertebrates. WGD is extremely common in plants and is now recognized as a major factor in Darwin's "abominable mystery," the rapid diversification of seed plants.
One advantage of WGD is that it automatically duplicates all cell networks, thus having one copy to do its original job and leaving another free to adopt a new task.
Further steps have to include rewiring the proteins, DNA sites and RNA molecules in new ways. For proteins, as we discussed in a previous blog, the rewiring is facilitated by the modular organization of proteins into domains. Since molecular interactions are domain-specific, domain swapping can change the connectivity of a protein to other proteins or to DNA.
DNA recognition sites are often carried on a particular class of natural genetic engineering tools called "mobile elements," which can duplicate themselves and move in one step to new locations in the genome. Many network-specific interaction sites have been localized to various mobile element types, and their role in functional networks has been documented, including one needed for pregnancy. The capacity of mobile elements to coordinate distant genetic loci was first described 55 years ago by Barbara McClintock.
We know less about regulatory RNAs because our recognition of their importance is so recent. But the available evidence identifies mobile elements as a major source of these so-called "non-coding" RNA molecules. Many mobile elements are highly variable and can modify and then disperse regulatory RNA sequences rapidly.
In this blog, we have seen that molecular biology has taught us deep lessons about two aspects of genome function:
(1) Genomes influence organism characteristics by encoding networks in a distributed fashion, not by the "one gene - one trait" model envisaged by early 20th Century genetics pioneers;
(2) Genomes change structure by rapid duplication and natural genetic engineering events that can happen at multiple locations (or even over the entire genome) in a short period of time.
What I find gratifying is that both these 21st-century ways of thinking about the genome fit so well in elaborating an evolutionary scenario. Although the scenario contains many gaps, the DNA record gives confidence that it points us in the right direction.
Let's just say, for the sake of it - hypothetically, not arguing the fact for now - that there is some kind of sentience (however unimaginable it might be for us) associated with one-celled organisms. Perhaps we shouldn't use the word "intention" as it is almost impossible, no matter how careful we might be in a rational sense, to avoid the conditioned sense of that word "intention" - that is, involving a fully conscious being such as we assume ourselves to be - to affect how we use it.
So, what if there is some kind of sentience associated with one celled organisms, and that there is a - dare I say it - directionality implicit in their actions that is associated with that sentience.
Nothing here is meant as proof, or as logical steps toward a conclusion - we're still at a hypothetical stage - what if we assume this sentience, and then go look at the data again, will it look different in any way?
James mentioned Nakagaki awhile back - he did some wonderful experiments showing the capacity of a one celled organism to solve a maze. And a Scottish biologist, Anthony Trewavas, has shown what sure looks like "intentional" or at least, remarkably intelligent behavior in plants.
But I think for most people nurtured on a purely non-mental, non-conscious understanding of science, these experiments could fairly easily be interpreted along the lines of a non-mental "intention" (if one can comfortably entertain such a notion).
However, things get a bit more controversial with psychologist Harry Hunt's claim that 'sentience" - that is, the "feeling" of being alive, or what Nagel calls "what it's like to be" alive or "aware" in some sense - may extend to one celled organisms. (to be continued)....
http://www.businessweek.com/articles/2012-06-27/making-human-organs-on-a-chip#r=read
Note the necessity to provide environmental and interactive cues and stimuli to evoke developmental and functional responses from the activated segments of the genome in each "organ on a chip". The implications go beyond normal functioning, I think. Any such channels can also be influential/available for genetic modification, too.
The teaser about a "human on a chip" consisting of a Lego-linkage of all the appropriate organ-chips is even more to think about. E.g.: how and if genital "organs" and their cells are affected by genomic innovation elsewhere in their phenotypic instantiation (i.e., the living organism). (Aside from dying with it if some flaw kicks in.)
It might be possible to observe any such interactions "on the fly"!
in reference to your point': Consider a checkpoint', this sounds like the slime mould of Toshiyuki Nakagaki et al. F.e. in Nature vol 407 28 sept 2000 2000:
"To maximize its foraging efficiency, and therefore its chances of survival, the plasmodium changes its shape in the maze to form one thick tube covering the shortest distance between the food sources. This remarkable process of cellular computation implies that cellular materials can show a primitive intelligence" .
Right?
The work of Nakagaki and his colleagues is an example of goal-oriented cognitive cell behavior (http://www.huffingtonpost.com/james-a-shapiro/cell-research_b_1559647.html).
Checkpoints are also cognitive and goal-oriented, But they serve different functions in cell biology and multicellular morphognesis.
In cell biology, the idea of checkpoint is that of a self-monitoring process that detects incomplete or damaged steps in the cell division cycle (http://www.huffingtonpost.com/james-a-shapiro/cell-cognition_b_1354889.html ). When a problem is discovered, the checkpoint apparatus holds up parallel steps in the division cycle until the delayed or damaged step can be corrected or completed. Then the checkpoint block is released so the division cycle can continue.
Note that the checkpoint system is inherently cognitive. It involves sensing, evaluation and decision-making to guide the biochemical and/or biomechanical events in cell division. I used to use the term "computational" to describe this, but the role of sensory inputs makes "cognitive" a more appropriate word.
Please let me know if the explanation is clear.
yes, clear, thank you, but terms like 'sensing' 'evaluation' and 'cognitive' are intentional. So my question remains, how do you get form mechanisms - i.e. the interactions of atoms- to this intentional behavior of cells, so quickly?. Where in the process in do these intentions emerge, get in?
cfr the question of Haldane (see his quote 07:11 AM on 06/21/2012 below): the brilliance of his formulation is, of course, that you easily can deny that there's a ghost in the machine, but to deny any logic in your own brain would be well... let's say: quite self defeating.
What are you're ideas on this?
i am not quite sure if i get what you mean, but I venture to doubt your 'Science is based on direct observation'.
At least you need to know where to look. You never observe black holes directly- as far as I know. Same for Higgs, f.e. And we never observed macro-evolution directly, for that matter. ;-)
Berthajane Vandegrift
A Few Autistic Questions about Freud, Marx and Darwin
No organism is capable of having "adaptations.... organized by the entire creative system". Instead, these are the result of biological and physical factors affecting the population in which these occur, and, moreover, they are constrained by the prior genealogical - what is known in biology as phylogenetic - history. (This is why, for example, it's impossible to "engineer" in reverse, a chick embryo so that it could hatch as a distant, extinct relative, a tyrannosaur.)
The Gould and Vrba (1982) term for modifying and reusing an evolutionary invention for a new purpose is "exaptation" (e.g. http://www.ncbi.nlm.nih.gov/pubmed/11038582).
Molecular genetics and cell biology focus on events in individual cells. There are many results which indicate that large-scale genome changes take place in single cells, either during independent vegetative growth on in the pre-germinal tissue of a multicellular organism.
The clearest examples are whole genome duplications that follow interspecific hybridization (http://shapiro.bsd.uchicago.edu/ExtraRefs.WholeGenomeDoublingCriticalStagesEvolution.shtml). These duplications are often followed by periods of heightened genome restructuring.
For major evolutionary changes, not all cells need to change in the same way. In fact, it is better if different cells undergo different variations because only a minority are likely to be successful.
It is best to think of natural genetic engineering as evolutionary experimentation. There is no reason to be believe that cells can predict what will work, but they can make changes in a way that makes it more likely that changes will prove functional and not detrimental (http://www.huffingtonpost.com/james-a-shapiro/natural-genetic-engineering-evolutionary-outcomes_b_1572730.html).
our threat is dead so to speak, so I hope you don't mind my answer here
As Darwin’s friend W. Greg stated in On the failure of 'Natural Selection' in the case of Man ‘ in this case ( humans, hp) adaptation is made.. by intellectual and moral efforts and qualities, which leave no stamp on the corporeal frame”. Knowlegde doesn’t fit well in a theory of differential (gene)reproduction. If you don’t mind a sweeping statement: K. Gödel didn’t come up with his incompleteness theorem to outbreed his cousins. Btw, he eventually wanted to refute any naturalistic explanation of the mind, but he never did. Haldane (1932) came pretty close, I think: ‘if my mental processes are determined wholly by the motions of atoms in my brain, I have no reason to suppose that my beliefs are true. They may be sound chemically, but that does not make them sound logically. And hence I have no reason for supposing my brain to be composed of atoms.”
’under this replication-centered perspective, the emergence of complexity is an enigma’ (E. Koonin, 2012, 414). We know that our ‘connectome’ is quite complex (and this poses some quite complex questions). Indeed, our connectome is ‘connections ‘all the way down’ ‘.I am trying to catch up with genetics, because I want to learn how far down that is to make it sound logically. 'Randomness’, stochastic independency, is a very tricky concept. And dice a tricky model, for that matter.
I think you see some of the basic issues. I invite you to read my book, if you have not done so already. You will find out some of what we currently know about the cellular tool box for natural genetic engineering and how it has been used in genome evolution. We know that cells can control when and where the genome engineering occurs. The missing piece is figuring out how the use of these tools is regulated in a way that promotes novelty and success.
thanks. But Haldane and Goedel and others saw them first!- actually L. Boltzmann was the first! Instead of mutation, selection and reproduction, I think we need to think in terms of computation. Computation is more about ascent rather than descent -or novelty if you wish. I think the missing piece you are talking about is information. At present we don't have a useful theory of information yet.
I'll read your book, once I've finished my huge reading list! In the meantime, I will be glad to follow your posts- and make this occasional remark.
Berthajane Vandegrift
A Few Autistic Questions about Freud, Marx and Darwin.
You heard correctly. Both microbes and larger organisms increase their DNA change activities under stress.
Barbara McClintock spoke about this her Nobel Prize lecture (see http://www.huffingtonpost.com/james-a-shapiro/barbara-mcclintock_b_1223618.html?ref=science for the link and other references).
I have posted list of references on this subject in tabular form (http://shapiro.bsd.uchicago.edu/TableII.7.shtml) and more extensively at http://shapiro.bsd.uchicago.edu/ExtraRefs.CellularRegulationNaturalGeneticEngineering.shtml (pay special attention to the "Adaptive mutation" heading, which covers the microbial cases you heard about).
Berthajane Vandegrift
A Few Autistic Questions about Freud, Marx and Darwin
A very basic example is where one Lego is the coding sequence for a protein but it lacks the Lego needed for that sequence to be transcribed into RNA. A mobile element (jumping Lego) can insert upstream and provide the necessary transcription signals. Then the protein is synthesized because a needed messenger RNA copy can be produced.
One step more complicated is where you have a coding sequence Lego and some but not all of the transcription signal Legos. If one new Lego X is added, transcription can take place in cell type A. If a different Lego Y is added, transcription takes place in cell type B.
Do these basic examples help you begin to see how a system is built up in the DNA?
Conaco C, Smith Bassett D, Zhou H, Arcila ML, DEGNAN SM, Degnan BM and Kosik KS. 2012. Functionalization of a Proto-Synaptic Gene Expression Network. PNAS, in press.
Kenneth Kosik: 'The critical step in the evolution of the nervous system as we know it, was not the invention of a gene that created the synapse, but the regulation of preexisting genes that were somehow coordinated to express simultaneously, a mechanism that took hold in the rest of the animal kingdom'.
Thanks for bringing us back to networks.
There are different ways network evolution can take place. One is to alter the conditions for expression of an established network, as in the case you cite. Another is to reconfigure the network so that it operates differently. That is, the network may acquire new inputs, new outputs, or execute different interpretations on the input information.
Because they operate in a combinatorial fashion, networks can display great variety using a limited number of interacting components. This is a far more flexible manner of genome coding than the single gene determination envisioned almost a century ago.
May be I am wrong (I am not a biologist), but as far as I know we are the only eukaryote on this planet that came up with a theory of evolution.
Humans(for instance) are all different but yet all still humans. Key cells are affected and then forced to react by a legion of variables, so many variables in fact they're incalculable, so (for now) we may as well refer to them collectively as chaos. This chaos of variables takes away predictability and forces uncertain directions. No key cell would intentionally chose to be uncoordinated if it had intent, but sometimes being an uncoordinated human has its benefits in spite of its self.
Every snowflake is different but every snowflake is still a snowflake. Can I infer from this that a snowflake's molecules reaction to chaos shows intent/selfishness/survival/adaptation, or not ?
Good to have you back in the discussion.
I think the comparison of cells to people (who can act stupidly, sometimes, but never chaotically, except when they have an infarct) is better than to snowflakes. Snowflakes are not alive and only have one response, which is to melt. We and cells are far more versatile.
The last thing a cell wants is chaos, even in the non-linear dynamics sense. It has to be able to change and adapt in order to survive. Being unable to do that, either because of lack of order or because it is trapped in an attractor, would be lethal to a cell. That is why I emphasize self-monitoring and self-correction as examples of what I call cell cognition (http://www.huffingtonpost.com/james-a-shapiro/living-cells-complex-syst_b_1204827.html and http://www.huffingtonpost.com/james-a-shapiro/cell-cognition_b_1354889.html).
Since you are familiar with the behavior of assemblies, it would be good to have your substantive perspective on cells as self-regulating and interacting entities.
By the way, I read every word of your articles and every comment very carefully and often times more than once, so if you don't see a comment from me it doesn't mean that I'm not in the classroom.
http://www.bioone.org/doi/abs/10.160/0022-2585%282007%2944%5B50:GDBCPF%5D2.0.CO%3B2
http://www.nature.com/hdy/journal/v82/n1/abs/6884120a.html
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-3032.1937.tb00911.x/abstract
There's separate gene pools, little to none-interbreeding, segregated niches, and some putative morphological differences. That satisfies most species definitions for most zoologists.
They are a text-book example of speciation that doesn't appear in text-books. I'm not so sure about the last one, it could be other Culex molestus, lots of synonymy, and I certainly am not an insect taxonomist (oh, no, definitively not) but I think it's the same.
The BioOne link was not available. The title would allow us to find it in PubMed.
Culex pipiens pipiens (Diptera: Culicidae) in New York
It's interesting because it seems that a similar phenotype/ecotype appeared independently in the Americas and Europe.
You're putting words in my mouth and using a term that is a fig leaf to cover our ignorance.
I never said that natural genetic engineering processes come from a cell's intent. I only say cells apparently use them in a cognitive way, based on sensory inputs about internal and external conditions. Intent in using DNA restructuring is OK with me if we keep it within the ambit of doing what is needed to ensure survival, growth and reproduction.
I have trouble with the word "emergent." I think it is used to describe system-wide properties that we do not understand in terms of the components and their interactions. If we recognize that it is code for an unsolved problem, that's OK. But my experience is that many people use the term as though it means something.
I don't think I need to explain what Hox genes are, considering that we are only 5 people here, this family of genes are responsible for our branching, metameric, polar, bauplan. Evolutionary biologists recognize that this entire family of genes responsible for shaping our, literally, come from one or two genes that increased in number, and hence in function. It's impossible to know why it happened, it's beyond our reach, but twe do know our possibilities. Whether we call for DNA duplication accidents, hybridization, incomplete recombination, or mobile elements, we are aware that a cell can't predict its environment beyond its sensing capabilities, hence, even if it increased variability under stress, it wouldn't be truly shaping its evolution, it seems like the evolutionary forces that, by the way, can explain the appearance of these mechanisms, will have the last word over both the mechanism that allowed this variation, and the emergent properties of metameric/allometric growth.
You are ascribing more functionality to Hox complexes than they possess and refusing to recognize their importance in the evolution of all bilaterally symmetric animals (bilateria), which apparently all posses them.
The Hox complexes are linear combinations of coding sequences for about eight regulatory proteins that each possesses a homeobox DNA-binding domain (whence the name). The Hox complexes interpret body segmentation signals and activate the morphogenetic functions appropriate to build each segment. Intriguingly, the different homeobox proteins are active along the body in the same order they are encoded in the DNA.
Hox complexes are complex spatially oriented microprocessors that interpret prior body plan information and communicate it to the appropriate downstream functions, presumably by activating transcription. They are found doing similar specification functions in animals which have completely different patterns of embryonic development, like insects and mammals.
It seems the ability to interpret body plan determination has remained critical to all bilateria. Once one early organism in the pre-Cambrian period succeeded in constructing the original Hox complex from duplicated coding and regulatory sequences, it has been retained and modified to integrate into a number of distinct developmental systems. The modifications seem to be both in the coding and regulatory sequences.
I think it is reasonable to argue that the Hox complex is one of the natural genetic engineering success stories and constitutes a major evolutionary invention necessary for execution of bilaterian morphogenesis.
For example, it's mathematically provable that, in the light of reduced horizontal transfer, meiosis (recombination, rather, but I'm talking about the final product here) increases variability, and hence increases the chances of an organism's progeny to survive. So it makes perfect sense to say that there's good chances that meiosis is an adaptation that appeared due to selective pressures against endogamic populations. So the existence of that "natural engineering process" can be explained through "conventional" evolutionary paradigms. But we cannot account for the existence of selective pressures, or of gene drift (nor am I saying that you are intending to do so) using cellular "cognition" or "natural genetic engineering". So which model encompasses the other? "Conventional" evolutionary theory, so there's no paradigm shift.
The same can be said about horizontal gene transfer, hybridization, mobile elements, aneuploidies, and so on... So are organisms shaping their evolution in response to the environment or has evolution selected against organisms that didn't...let's say...accept their inner chaos in an organized manner, which lead us to the illusion of intent?
My comments tend to be reactive, so I'll try to have a different approach this time.
I agree that there's mechanisms that certain cells in different groups have that increase variation, some depend on stress, some seem to have evolved from stress-response, but no longer are that way.
I also agree that point mutations are just one of many mutational events, recombination is mutation in itself. The reason why there is a population genetics approach towards point mutations in the study of evolution is more pragmatic than predictive. That is, nobody is suggesting that the appearance of useful properties or proteins is ruled by the tirany of u (mu).
I do agree that horizontal gene transfer (both of specific elements and by means of hybridization), mobile elements, gene duplication, domain shuffling, network "repurposing", symbiosis and other mechanisms play an important role in evolution.
Welcome back to the discussion. I hope you will agree that it is improving in tone and quality.
I respond to your recent 12:37 PM comment here because I have no "reply" button to use at the bottom of your comment.
I think you are right that it is important
(1) to explain as much as possible empirically what we mean by the terms we use, and
(2) make every effort to understand what the other guy is meaning and trying to say.
On the subject of cognition and intention, my own contributions to (1) include my comments posted at the following times:
05:21 PM on 06/14/2012,
17 hours ago ( 8:54 PM),
16 hours ago ( 9:07 PM),
16 hours ago ( 9:32 PM),
22 minutes ago ( 1:05 PM) and
9 minutes ago ( 1:18 PM).
I hope you will have a chance to read those replies and respond to them. I know it is not easy because they are scattered in several threads, but it will help all of us if you can make the effort.
http://shapiro.bsd.uchicago.edu/Reply%20to%20Larry%20Moran.pdf