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Computational Geneticists Revisit A Mystery In Evolution
Science Daily ^ | Date:Posted 8/8/2002 | Editorial Staff

Posted on 08/16/2002 10:27:48 AM PDT by vannrox


Reprinted from ScienceDaily Magazine ...

Source:             Stanford University
Date Posted:    Thursday, August 08, 2002
Web Address:   http://www.sciencedaily.com/releases/2002/08/020807065302.htm


Computational Geneticists Revisit A Mystery In Evolution

You and I are both human, with hearts that beat at roughly the same rates, nervous systems that churn out just about the same chemicals, bodies that are similar enough to peg us as people and not chimpanzees. But despite the fact that we both belong to the same species, our genes are pretty different. Only half the genes are identical among siblings who aren't twins, for example, and for most of us, the degree of genetic relatedness is much smaller. Why, biologists first asked 60 years ago, do members of the same species have such similar traits, or phenotypes, despite the fact that they have such diverse genes, or genotypes? They couldn't fully explore that question until now - when, aided by computers, they can sift through mountains of experimental data. In the June 24 issue of the Proceedings of the National Academy of Sciences, senior research scientist Aviv Bergman of Stanford's Center for Computational Genetics and Biological Modeling (CCGBM) and postdoctoral scholar Mark Siegal of the Department of Biological Sciences provide a surprisingly simple answer.

Invariant traits - such as having five fingers to a hand instead of four or six - don't become universal because Nature has somehow selected special genotypes that faithfully direct development of the trait under a wide variety of conditions, the researchers argue. Instead, they show, it is the complexity of our genotypes - the many genes that interact in networks during development, inhibiting and activating each other and even regulating themselves - that provides fidelity. Indeed, Bergman and Siegal show that any functional genetic network that is complex enough has this built-in property of fidelity. This is true whether natural selection on the phenotype produced by the network during development is strong, weak or absent. Natural selection may be important in shaping traits that aid in reproduction and survival, but Bergman and Siegal show that it doesn't matter much during development, when, biologically speaking, all roads lead to Rome.

''We're taking a more sophisticated view of evolution as a process,'' says Bergman, who co-directs the CCGBM with Marcus Feldman, the Burnet C. and Mildred Finley Wohlford Professor in the School of Humanities and Sciences. ''We need to take into account not only the genetic system by which the hereditary information is passed on from one generation to the next, but also the developmental system by which the information contained in the fertilized egg is expanded into the functioning structure of the reproducing individuals.'' Researchers at CCGBM, established in 1997 with a grant from the Paul G. Allen Foundation, conduct interdisciplinary research into quantitative problems of biology.

''Evolutionary biologists tend to think of natural selection as the first possibility of a mechanism for explaining most things that they observe,'' says Siegal. ''So it's natural that the first attempts to explain this disconnect between great genotypic variation and little phenotypic variation was through natural selection.''

In 1942, even before it was known that genes were made of DNA, British biologist Conrad H. Waddington coined the term canalization to describe the ''funneling'' that occurs during development to produce just a few end products, or traits, such as the beautifully patterned wings of a butterfly. He envisioned development proceeding the way a ball rolls down a mountain, traveling mainly along well-worn grooves and having the option of rolling one way or the other at only a few forks in the road. The ball rolls to the right, and the result is, say, development of an elaborately patterned forewing. It rolls left, and a different-looking hindwing forms. The puzzle that attracted Bergman and Siegal was not so much the nature of the genetic switches that operate at the ''forks'' but instead what causes the ''grooves'' that keep development faithfully rolling along when both environmental disturbance and genetic mutation could potentially set it off course.

''You can throw a lot of insults at an organism - either genetic ones by mutation or environmental ones by changing the temperature or changing the chemical composition of the food - and in spite of all of those insults, development is pretty robust,'' explains Siegal, who also conducts evolutionary research on fruit flies in the laboratory of Bruce Baker, the Dr. Morris Herzstein Professor in Biology. From larvae incubated in a lab at 18 or 28 degrees Celsius, for instance, similar-looking flies will develop, even though chemical reactions are twice as fast at hotter temperatures than colder ones. The developmental pathway and end products (traits) seem immune to such insults.

Indeed, some biologists argue that canalization may have evolved as a response to environmental change. Under this scenario, Bergman explains, ''When mechanisms evolved to dampen the effect of environmental variation on the phenotype, as a side effect they also happened to buffer genetic variation.'' But the results of Bergman and Siegal suggest that environmental perturbation is not necessary for canalization to evolve. ''We don't know all the details of what makes that funneling process work,'' Siegal admits. ''But our contribution to it is giving one possible reason that hasn't in our view been considered enough.''

Scientists used to think that developmental fidelity evolved via natural selection, principally through survival and reproduction of organisms with redundant genetic systems - that is, ones with copies of important gene sequences. But Siegal and Bergman's results indicate that redundancy may only be one small manifestation of a bigger theme: the complexity of gene networks. In short, more complex systems are more resistant to change in their outputs.

''It is typically assumed that important properties of organisms are crafted by natural selection,'' says Dmitri Petrov, assistant professor of biological sciences. ''What Siegal and Bergman show is that robustness in the face of mutation, or canalization, may be a byproduct of complexity itself and therefore that robustness may be only very indirectly a product of natural selection.''

Says Siegal: ''It might be that the complex nature of the genetic system itself is going to give you canalization independent of natural selection. This complexity goes beyond mere redundancy, incorporating all kinds of elaborate connections in the gene network.''

That doesn't mean natural selection doesn't play an important role. Continues Petrov: ''Natural selection has shaped the genetic networks of complex organisms so that they produce appropriate phenotypes - the more highly interconnected these networks are, the more robust the corresponding phenotypes are. The importance of this result is that it shifts the focus of the field away from abstract models of natural selection and toward actual genetic networks. In so doing, it will provide a new perspective for analyzing and understanding the current outpouring of genetic data in model organisms.''

A new perspective could prove useful - because invoking natural selection to explain the disparity between genotypic and phenotypic variation has several problems. First, a prerequisite for canalization is genetic variation - but if selection for a trait is too strong, it shrinks the gene pool. ''Once that limits the genetic variation, it removes the pressure to have canalization,'' Bergman says.

Second, modeling has shown that if nature ''selects'' a trait, canalization evolves - but very, very slowly, over millions and millions of generations. ''When you start thinking about time scales like that,'' Siegal says, ''you have to wonder whether any evolutionary force can be consistent over that amount of time to actually cause the outcome that you see.''

And third, what's ''optimal'' today may not be optimal tomorrow. Says Bergman: ''As [scientist Stephen Jay] Gould said, as the environment changes what was once fit may not be fit today, and with further change in the environment could become fit again.''

For their project, Siegal and Bergman chose to model an abstract system that is important in the development of most organisms - transcription factors, or proteins that regulate the expression of genes. In the model they developed, 10 genes each encode a protein that in principle is capable of regulating the expression of each of the other nine genes, as well as itself. To compare the complexity of the abstract system with that of an actual system, consider that yeast, for example, has about 6,000 genes, around 500 of which regulate each other.

Bergman and Siegal's collaboration comes at a time when - thanks to the use of microarray technology in a new field known as functional genomics - scientists have greater knowledge about sophisticated gene interactions during development. This technology helps scientists analyze the functions of genes in an organism's genome - all the genes that make up its genetic blueprint - and allows them to look closer than ever before at the intricacies of heredity. So, although the song remains the same as that sung by previous giants of biology, such as Darwin and Gould, Bergman and Siegal are studying the individual musical notes to better understand how evolution's song plays out.

''The evolution of genetic robustness is a whole new game now that we have the results from Drs. Bergman and Siegal,'' says Gunter Wagner, professor of ecology and evolutionary biology at Yale University. ''[It] shows that selection against lethal mutations [those that make the network incapable of producing any phenotype] can lead to the evolution of mutational robustness of any character state, even in the absence of stabilizing selection for that character state itself.''

Says Siegal: ''In many ways canalization was sort of a smokescreen that was dividing evolutionary biologists and developmental biologists. The developmental biologists were studying their genetic networks and the evolutionary biologists were in the abstract saying, 'Well, these networks must have evolved to produce certain properties, like robustness in the face of mutational insult.' But since we have shown in our model that it's actually the nature of the developmental system that can give you this property, they're really not two separate things to study. They're the same thing to study. I think a lot will come out of looking at actual genetic networks and how the structure of those networks gives them the property of being robust.''



Copyright © 1995-2002 ScienceDaily Magazine | Email: editor@sciencedaily.com


TOPICS: Culture/Society; Extended News; News/Current Events
KEYWORDS: bible; computational; crevolist; discovery; diversity; evolution; gene; geneticist; human; mystery; nature; phenotypes; science
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To: gore3000
Read a book on this stuff. Wolfram shows you can enumerate every program in many simple systems and still get non-trivial results above a certain (and suprisingly low) threshold of complexity. Programs also tend to behave similarly. In other words, the popular notion of just bashing random locations in a complex program most likely resulting in garbage results is wrong. But, as these people show, evolution as the only input to how natural programs are organized is also probably wrong.
21 posted on 08/17/2002 5:39:48 AM PDT by eno_
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To: <1/1,000,000th%
Random programs, but non-random results. Genes as we know them on Earth might be just one way for life to emerge, and the rules that govern how and where this can happen are probably more general than terrestrial biology.
22 posted on 08/17/2002 5:42:26 AM PDT by eno_
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To: <1/1,000,000th%
I'm sure I'm going to be sorry I asked, but which is it? Random or not random?

Non-random of course. Programs do not write themselves at random and what we have in the development of an organism is a very tightly controlled process which has to proceed exactly. Also the evidence in the article of this process ignoring mutations, shows quite well that it cannot be changed at random.

23 posted on 08/17/2002 10:08:28 AM PDT by gore3000
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To: eno_
But, as these people show, evolution as the only input to how natural programs are organized is also probably wrong.

So what is supposedly this other input? Also can you give some examples of these simple systems that give supposedly complex results?

24 posted on 08/17/2002 10:11:22 AM PDT by gore3000
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To: gore3000
At www.wolframscience.com you can browse cample pages from his book, and, if you have Mathematica, you can download and run the code that actually conducts his experiments.

That "other input" to how genetics works are the laws of complexity theory. In other words, random mutation and evolution do not have a free hand in modifying genomes. There are more basic laws of complexity, information theory, expressive power of systems, etc. at work. Biochemistry meets information theory.

25 posted on 08/17/2002 10:23:23 AM PDT by eno_
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To: eno_
That "other input" to how genetics works are the laws of complexity theory. In other words, random mutation and evolution do not have a free hand in modifying genomes. There are more basic laws of complexity, information theory, expressive power of systems, etc. at work. Biochemistry meets information theory.

Sounds a lot like intelligent design to me. Information does not create or arrange itself.

26 posted on 08/17/2002 12:53:27 PM PDT by gore3000
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To: gore3000
...biggest cult of oxy-moonie-morons---art bells!

Like patrickhenry...

"search for the creator via evolution"---

"total--only evolution" too---

The papal encyclical rightwingprofessor-whack thinks/interprets---"professes evolution"...

Nebullis..."preschool evolution---INTENSIVELY"---

donh..."if the sun can create crystals-snowflakes...human life would certainly follow"---

also by donh...Hitler and nazi germany were all Christians---creationists!

dominick harr..."just like a ball bouncing down the stairs----evolution created everything"---

jennyp..."anarchist evolutionary capitalism(natural)---Christianity(manmade) is communism"---

and patrickhenry doesn't know..."if prior to darwin---if science existed"...

SkyRat...Divine hammer-retribution from above via evolution!

exdemmom...evolution is the "lug wrench" that fixes science--biology/life!

Running sores of evo schlock!

Few new ones by the vade--junior--ph evo cult...

More schlock---latests(evo proof/matches/links)...

over---abundance of dung for beetles...schlock providence/miracles

ground depressions on earth surfaces collect liquids producing ponding---more spontaneous schlock opportunities/diversity...

motion/movement is created via biological interference/resistance in gravitational force fields...

foot/toe ground contact---attractions/balance...

standing/walking/running upright

amazing...dancing too!

My own...how evo schlock made us...

Insects vibrate molecules and gas particles---sound...and how humans procreate via words/instruments---music/songs.

I get it!

This schlock is so simple...natural---unplanned---no design!

Presto...mommies/daddies---babies!

27 posted on 08/17/2002 1:28:17 PM PDT by f.Christian
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To: gore3000
Make of it what you like, but it is more likely that Wolfram's and other complexity theory work will show that complex systems can emerge from random origins.
28 posted on 08/17/2002 6:54:43 PM PDT by eno_
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To: eno_
Make of it what you like, but it is more likely that Wolfram's and other complexity theory work will show that complex systems can emerge from random origins.

I really wanted to learn more about it, was hoping you could give a fuller explanation.

29 posted on 08/17/2002 10:32:38 PM PDT by gore3000
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To: gore3000
Well, I'm a little out of my depth in composing a one paragraph summary of complexity theory, but here goes: Simple programs can produce complex results. The power of the programs need only reach a very low threshold before the results yield complex patterns that are not easy to predict. These systems are simple enough that you can enumerate every program in those systems, try them, and see if complex results are produced. This might mean that various natural systems where chemicals constitute systems that contain and process information can emerge and produce complex results without any outside organizing impetus.
30 posted on 08/18/2002 6:39:52 AM PDT by eno_
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To: vannrox
Nice article. Thanks for posting this.
31 posted on 08/18/2002 4:15:47 PM PDT by Nebullis
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To: The Great Satan
You are a complete igoramus

Snicker!

32 posted on 08/19/2002 5:18:50 PM PDT by AndrewC
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