"The emerging principles of regulatory evolution"

[rwatts]

Hi All,





I have the terrible urge for another essay. 



What got the feeling started was trying to comprehend this paper:-



Modular Evolution of DNA-Binding Preference of a Tbrain Transcription Factor Provides a Mechanism for Modifying Gene Regulatory Networks



In trying to come to grips with parts that put splinters into my fingernails when scratching my head, I found myself backtracking to read various reference papers, including one on Hox genes and then this:-



Emerging principles of regulatory evolution




It’s this last paper, “Emerging principles ...” which will be the topic of the following set of essays. This is fascinating stuff, something which I’d been aware of, but not really appreciated until now, and I think I understand enough to begin writing.




Along the way I finally found out how and why:-



1) this relatively new stuff might be so important to morphological evolution (perhaps even outweighing things like gene duplication), and

2) why researchers spend so much time concentrating on relatively little things like stripes on flies and colour patterns on butterfly wings, and from these studies draw more general conclusions about macro evolution, and

3) why so many of the articles I read, reveal that the same gene being is used in many different parts of a developing organism, and in seemingly unrelated ways and

4) why some researchers often appear oblivious to this kind of research and perhaps at times might show a degree of hostility towards it.



Besides, some very recent research has reported this:-




Multiple evidence strands suggest that there may be as few as 19 000 human protein-coding genes



Ouch. Once upon a time our protein coding genome, was thought, based on the evidence then available, to be of the order of 100,000 genes. Then came more recent research, often centered on the Human Genome Project. This new evidence revealed only some 20,000 genes. Now it could be as low as 19,000 genes.



So where can the massive amount of variety in animal form come from, given evolution from a common ancestor?



Well the article I will be attempting to describe in the following set of essays shows what one of the solutions is likely to be, and why this is so. I think it might solve some of the problems associated with convergent evolution. It’s a way of genome evolution that minimizes pleiotropic effects. Pleiotropy occurs where one gene affects multiple traits. So a change to that gene affects those multiple traits, and while one or two trait alterations might be beneficial, the rest could well be harmful.


It’s interesting stuff. It’s been around for some 20 years or so, but is not generally appreciated by those into the more orthodox studies of evolution. The first paper I link to, “Modular evolution ...” questions some of the inferences drawn by this research which was published in 2007. But that was seven years ago, and the “Modular evolution ...” paper is today.

Nevertheless, both papers stress the importance of changes to gene regulatory systems and regulatory networks.


For now I will leave you with the abstract:-





Benjamin Prud'homme, Nicolas Gompel, and Sean B. Carroll, Emerging principles of regulatory evolution, PNAS published online May 9, 2007; doi:10.1073/pnas.0700488104

Understanding the genetic and molecular mechanisms governing the evolution of morphology is a major challenge in biology. Because most animals share a conserved repertoire of body-building and -patterning genes, morphological diversity appears to evolve primarily through changes in the deployment of these genes during development. The complex expression patterns of developmentally regulated genes are typically controlled by numerous independent cis-regulatory elements (CREs). It has been proposed that morphological evolution relies predominantly on changes in the architecture of gene regulatory networks and in particular on functional changes within CREs. Here, we discuss recent experimental studies that sup- port this hypothesis and reveal some unanticipated features of how regulatory evolution occurs. From this growing body of evidence, we identify three key operating principles underlying regulatory evolution, that is, how regulatory evolution: (i) uses available genetic components in the form of preexisting and active transcription factors and CREs to generate novelty; (ii) minimizes the penalty to overall fitness by introducing discrete changes in gene expression; and (iii) allows interactions to arise among any transcription factor and downstream CRE. These principles endow regulatory evolution with a vast creative potential that accounts for both relatively modest morphological differences among closely related species and more profound anatomical divergences among groups at higher taxonomical levels.


The question is, can I adequately describe the “Emerging principles ...” paper?

Stay tuned.




To be continued ....


[rwatts]

Introductions to science papers are often well worth a read because:-



1) They are the most readable part of the paper for the layperson.


2) They explain the historical background,

3) They explain what is being attempted and why it is being attempted.


4) In association with the abstract, and the conclusion, the lay reader learns what was discovered, and often what needs to be done in the future.



Thus it is with the paper I describe in this series of essays:-



Emerging principles of regulatory evolution




There was once a time when it was thought that one gene coded for one protein and that the human genome consisted of something like 100,000 genes. However, as scientists peered ever closer into the genome, thanks to advances in technology, their understanding changed considerably.

Studies showed that a lot of evolution happened by altering an organism’s embryonic development. Paedomorphosis or neoteny is a well known example, where juvenile features are retained by the adult. For example, the the timing of some feature in the embryo has been shut down early, leaving the adult form with a feature in its juvenile state. A recent reported example is the bird skull:-

Birds have paedomorphic dinosaur skulls



The human face shows features similar to the juvenile chimp and so is considered to be a paedomorphic feature derived from our common ancestor.

Thanks to technology, the study of molecular evolution came of age with the identification and functional characterisation of genes that governed development in model organisms. These are a small group or organisms that have features that make them useful for study, and so scientists tend to concentrate on their genetics in order to learn about genes in general. The mouse is a model organism for humans and mammals in general. It’s easy to breed, fast to breed, and because it has been well studied, then its genetics are relatively well understood. E. coli is another model organism as is the fruit fly Drosophila melanogaster which everyone has heard about.

It’s through the study of these organisms that researchers were able to learn much about developmental genes through the 1980s.

Then it was shown that networks of patterning genes orchestrate the formation of body parts. These genes mostly coded for two kinds of molecules, transcription factors and cell-signaling molecules. Transcription factors are proteins that bind to specific DNA sequences and thereby control the rate of transcription into messenger RNA of downstream genes. That is, genes that code for transcription factors, are genes that control other genes. And transcription factors can control the formation of other transcription factors and so on, and thus we have a network of genes. Cell-signaling molecules are generally proteins that move from one cell to another, initiating certain activities in the receiving cell. Typical examples are hormones and neurotransmitters. Hox genes are a classic example of a transcription factor, and one of the things they do during development is lay out the main parts of an organism’s body plan, i.e. head here, thorax there, and abdomen here for the insect.

Subsequently it was found that the formation of similar body parts and functionally equivalent organs was, across widely divergent organisms, “controlled by remarkably similar sets of orthologous pattern-regulating genes that have been conserved over hundreds of million years of evolution”.

This presented a paradox.

The paradox


As the authors of the article put it - “if all animals are built by using similar genetic tools, how did their seemingly endless morphological diversity arise?”

For example, if the families of hox genes between man, mouse and camel are so darn similar, then how come we look so different? Why don’t all humans have two humps on their backs, and why aren’t camels walking upright?





To be continued ....





[jordanriver]

Maybe you got all kinds of critters in your genome.

[klaus54]

Maybe you got all kinds of critters in your genome.

You actually do.

Learn genetics.

Learning being fun.

K54

[rwatts]

Maybe you got all kinds of critters in your genome.

Indeed, in several ways.

As Klaus said, learn. Learning can be fun.

[jordanriver]

Maybe you got all kinds of critters in your genome.

Indeed, in several ways.
.

well , I guess we can cross off #3
3. Fitting the Animals Aboard


if humans are learning to manipulate methylation, Yahweh certainly wouldn't have had any problems

that would leave plenty of room on the Ark,
maybe a big shuffleboard on the deck

and a gym for the primates to practice Zumba so that when they return to dry land they can do this

[klaus54]

well , I guess we can cross off #3
3. Fitting the Animals Aboard


if humans are learning to manipulate methylation, Yahweh certainly wouldn't have had any problems

that would leave plenty of room on the Ark,
maybe a big shuffleboard on the deck

and a gym for the primates to practice Zumba so that when they return to dry land they can do this

Wow, you ARE good!

Totally wrong, but a good and droll attempt.

I give it a "B-".

Hey Gurl, when ya are gonna start addressing the vast mountains of evidence against YEC. instead shooting spitwads at niggling details of biochemistry?

You DO know them there niggling details are what real scientists love?

K54

[rwatts]

if humans are learning to manipulate methylation, Yahweh certainly wouldn't have had any problems

If you read the paper I link you to JR, this has nothing to do with methylation.

[jordanriver]

If you read the paper I link you to JR, this has nothing to do with methylation.

Its about dna methylation (by epigenetic control) whether they acknowledge it or not.
Your genes have MULTIPLE OPTIONS each, and epigenome determines according to environment which is option to activate

[klaus54]

Its about dna methylation (by epigenetic control) whether they acknowledge it or not.
Your genes have MULTIPLE OPTIONS each, and epigenome determines according to environment which is option to activate

And this is relevant to a possible negation of biological evolutionary theory exactly how?

BTW, have you checked some geological facts lately?

It's so cute to see a fideist making spitwads. How many old-fashioned Bic pens do you need?

K54

[rwatts]

Its about dna methylation (by epigenetic control) whether they acknowledge it or not.

How did you work that out? (I might just as well assert that your last post to me was about fairies driving F1 racing cars whether you acknowledge it or not.)

[rwatts]

Continuing to describe the history leading up to our current understanding (as of 2007) of gene regulation and its role in evolution, the authors write:-


“A vast body of comparative studies has revealed that morphological differences among taxa are correlated with differences in developmental gene expression patterns, ...”



Of course correlation can be because of causation, but it does not necessarily mean causation. However this correlation did make some researchers wonder if the modification to gene expression patterns were behind morphological evolution as proposed here:-



Homeotic genes and the evolution of arthropods and chordates



This became an hypothesis to be tested and two ideas for the evolution of gene expression involved:-



1) changes in the activity or deployment of proteins, largely transcription factors described earlier, or



2) changes in the regulatory sequences that govern gene expression.




In the early 1990s, these ideas began to be sorted out.



First there was the issue of transcription factors like Hox proteins, showing relatively little divergence in biochemical activity over hundreds of millions of years of evolution.



Secondly, researchers found “unexpectedly complex and modular organization of the cis-regulatory regions of pattern-regulating genes”. Pattern-regulating genes are those, which, for example, govern the formation of stripes on fruit flies such as D. melanogaster. The authors write that “Most loci encoding pattern-regulating proteins were found to include multiple individual cis-regulatory elements (CREs), with each CRE typically comprising binding sites for multiple distinct transcription factors and controlling gene expression within a discrete spatial domain in a developing animal."



cis-regulatory regions are short regions of DNA outside of the gene they regulate. Proteins such as transcription factors bind to these and thereby control control the rate of transcription of DNA to messenger RNA (which often goes on to be translated into protein). Transcriptions factors can either act alone or in concert with other regulatory regions, for example, enhancers, short strips of DNA which promote DNA transcription or repressors which block DNA transcription.



Transcription factors are proteins which are long strings of amino acids (coded for by genes) curled up in rather odd-ball but stable ways. Most of the string is just there to provide protein structure but one or more regions amongst this structure are what are called “domains”. These domains provide the protein with its functionality, each domain giving the protein a different function. Some domains allow the protein to bind with other proteins, or with perhaps different chemicals altogether (say an iron atom). In the case of transcription factors, these domains allow a protein to bind with the cis-regulatory regions, and some factors have several domains, allowing them to bind with several different regions.



Now a gene can be expressed in different places and/or at different times in a developing embryo (one of those things scientists soon learned when they began to test early assumptions regarding genes). Transcription factors play a key role in determining these times and places of gene activity. Hence the transcription factors and their associated cis-regulatory regions provided genes with a degree of modularity, a degree of discreteness. For example, consider a gene encoding for a structural protein. We will call the gene “X”, and transcription factors (and their cis-regulatory regions) lying outside of X we shall label “A”, “B” and “C”. Gene X might be activated in the developing leg at time t₁ by transcription factor A, in the developing head at time t₂ by transcription factor B, and in the developing kidney at t₃ by transcription factor C. If this modularity did not exist and evolution happened at only at the level of structural gene (X in my example), then a change in X would affect the leg, the head and the kidney. It might well be an advantageous change for the leg, but will unlikely be advantageous to the head and the kidney at the same time. This phenomenon is what is known as pleiotropy and while there are documented examples of evolution being able to affect structural genes and overcome this problem, it does seem to provide a tangible limit on just how much can be expected of structural genes to change over time.



However, with these multiple of cis regulatory regions existing outside of a gene, each allowing transcription factors to bind to and effect gene expression, then changes to these regulatory regions may easily minimize the effects due to pleiotropy. Taking the above example, changes to A will limit X’s impact to the leg only, leaving its impact on the head and kidney unchanged.

As the authors write:-





The realization that the total expression pattern of a gene was the sum of many parts, each directed by distinct CREs, marked a profound change in concepts of gene regulation. The modular arrangement of CREs also had clear implications for evolutionary genetics, because it suggested a mechanism for how selective changes in gene expression and morphology could evolve in one part of the body, independent of other parts. [11]





This profound change in how scientists understood the meaning of the word “gene” had a profound change in how many scientists were beginning to understand evolution.



They saw the conservation of biochemical activity of the regulatory proteins, a conservation that united very different kinds of animals and other organisms across hundreds of millions of years. They also noted the divergence in expression patterns of the regulatory genes and that was associated with these very different kinds of animals. And so the modular organisation of these CREs provided “the basis for the general proposal that gene expression evolution, and therefore morphological evolution, would occur primarily through changes in cis-regulatory sequences controlling gene transcription”.



However, what seemed like a very good idea was not widely recognised at the time and, according to the authors, is still not fully appreciated.





To be continued ....



[rwatts]

And this is relevant to a possible negation of biological evolutionary theory exactly how?

On another forum a YEC told me that he'd read the paper on the dinosaur/bird tail transition, the paper I described in that other thread. He claimed it did not mention the word mutation.

Naturally, the whole paper was about mutation, and I counted over 120 instances of the word and words closely related to it.

YECs knowing what scientists mean, when said YEC is utterly clueless about a particular paper seems to be par for the course, in many cases. Going by what some YECs claim, it seems to be because they are Bible believers and so have a discernment and a wisdom the rest of us lack.

I mean, just what does one say????

[jordanriver]

How did you work that out? (I might just as well assert that your last post to me was about fairies driving F1 racing cars whether you acknowledge it or not.)

ok, Roland, you seem to be interested in Hox genes.

Are you on the verge of concluding that Hox genes are doing all their work on their own?

in your POST 2 you reported the paradox:
"The paradox


As the authors of the article put it - “if all animals are built by using similar genetic tools, how did their seemingly endless morphological diversity arise?”

For example, if the families of hox genes between man, mouse and camel are so darn similar, then how come we look so different? Why don’t all humans have two humps on their backs, and why aren’t camels walking upright?""

then you cited 'Homeotic genes and the evolution of arthropods and chordates' by Sean Carroll
where on page 484:
"We now know that Hox genes are regulated by many upstream factors, and that Hox proteins act as sculptors that modify the basic arthropod or chordate metamere by modulating the expression of potentially dozens of interactive genes, the products of which determine the cellular events of morphogenesis"

Roland, what do you think are some of those "upstream factors"

If the Hox genes are just "sculptors" then that would possibly explain the paradox ,
if by "sculptor", the writer is referring to the tool, the same wood chisel 'morphs' a variety of sculptures.

its just the tool.

Or do you think the Hox gene is a "sculptor" in the sense of being 'the craftsman' who uses the tool, and is not regulated by some other director?









[rwatts]

ok, Roland, you seem to be interested in Hox genes.

Are you on the verge of concluding that Hox genes are doing all their work on their own?

in your POST 2 you reported the paradox:
"The paradox


As the authors of the article put it - “if all animals are built by using similar genetic tools, how did their seemingly endless morphological diversity arise?”

For example, if the families of hox genes between man, mouse and camel are so darn similar, then how come we look so different? Why don’t all humans have two humps on their backs, and why aren’t camels walking upright?""

then you cited 'Homeotic genes and the evolution of arthropods and chordates' by Sean Carroll
where on page 484:
"We now know that Hox genes are regulated by many upstream factors, and that Hox proteins act as sculptors that modify the basic arthropod or chordate metamere by modulating the expression of potentially dozens of interactive genes, the products of which determine the cellular events of morphogenesis"

Roland, what do you think are some of those "upstream factors"

If the Hox genes are just "sculptors" then that would possibly explain the paradox ,
if by "sculptor", the writer is referring to the tool, the same wood chisel 'morphs' a variety of sculptures.

its just the tool.

Or do you think the Hox gene is a "sculptor" in the sense of being 'the craftsman' who uses the tool, and is not regulated by some other director?









JR, you asserted that:-

"Its about dna methylation (by epigenetic control) whether they acknowledge it or not."

I'm asking you how you managed to work that out (based on their paper)?

Or do you think the Hox gene is a "sculptor" in the sense of being 'the craftsman' who uses the tool, and is not regulated by some other director?

?

Hox genes have to be triggered by something else. And they can be regulated by other things (read my last post to find out what kind of things they can interact with). What's the biggie about that? If you are thinking of papers such as this:-

DNA methylation and differentiation: HOX genes in muscle cells

-then read the conclusion, before you try jumping up and down. And as Klaus asked, what on earth does this have to do with ToE being wrong, and a 6 day creation 6,000 years ago being correct?