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Using Statistics To Decipher Secrets Of Natural Mutation
Howard Hughs Medical Institute via ScienceDaily ^ | 2004-08-18 | Not available

Posted on 12/29/2004 12:11:51 PM PST by beavus

A new mathematical approach for analyzing the complex, subtle patterns of natural mutation in DNA will, according to its developers, help biologists understand how mutation contributes to evolutionary change in mammals.

The researchers, Howard Hughes Medical Institute investigator Phil Green and his student Dick Hwang, published a description of their new analytical approach and an initial application August 3, 2004, in the online early edition of the Proceedings of the National Academy of Sciences. Both are at the University of Washington in Seattle.

"Understanding naturally occurring mutations has been of great interest because mutations are major drivers of evolution," said Green. "However, it's surprising how little is still known about their causes."

Previous studies have revealed a number of biases in the rates of different types of mutational change. These arise in part from the innate biochemical characteristics of the four DNA nucleotide units – adenine, guanine, cytosine and thymine – that affect their vulnerability to modification and the accuracy with which they are replicated when cells divide. Particular nucleotide sequences, for example cytosine-guanine (CpG) dinucleotides, form "hotspots" – regions that are particularly vulnerable to alterations that convert one nucleotide to another, causing mutations.

To understand these biases, Hwang and Green sought to develop a flexible approach to analyze the process of "neutral DNA evolution," in regions thought to lack genes and other functionally important sequences. "If you want to get an unvarnished picture of the mutation process itself, uncorrupted by natural selection, you want to look at neutrally evolving DNA," said Green. "Mutations in DNA that is not functional should better represent the complete spectrum of naturally occurring mutations. Mutations are of course also occurring in the genes and those are of interest because they can create new phenotypes and cause variation among traits. Some of those mutations are advantageous and consequently quickly spread through the species, while others are deleterious and are weeded out. So genes and other features don't evolve at neutral rates."

"Apart from their intrinsic interest, we think understanding the underlying mutation patterns better will also help us in finding the functionally important features in the genome. Basically, it's a signal-to-noise issue, where the naturally occurring mutations are the 'noise' and the functional parts of the genome are the 'signal.' The better we understand the noise, the better job we can do of understanding the signals."

To begin to understand the patterns of DNA changes that result from neutral mutation, Hwang and Green developed a new version of a powerful statistical technique that they call "Bayesian Markov chain Monte Carlo sequence analysis." Basically, the technique enables them to feed in sequence information from genomes of different organisms and discern patterns that can distinguish models of mutational mechanisms.

According to Green, the statistical approach offers a powerful way to analyze models that are very difficult or impossible to solve analytically. "Until recently," he said, "the state of the art in the molecular evolution field was to use models that people knew were gross over-simplifications, but had the merit that you could solve them analytically. Without doing too much computation, you could make estimates of mutation rates of various sorts. However, the cost of that simplified approach was a model that really is unrealistic."

In particular, he said, the standard model treated all positions in the sequence as evolving independently of each other, rather than taking into account context effects, in which the identity of neighboring nucleotides influences the nature and rate of mutations.

"While a few other investigators have been working on how to take into account context effects, I think we are doing it in more rigorous, more complete way," said Green. Without such a rigorous approach, he said, models of evolution could give erroneous results regarding the effects of mutation.

"I think the more realistic you can make the model, the less likely you are to be led astray by drawing conclusions that really had more to do with the deficiencies of your model than with the underlying reality," said Green.

Hwang and Green tested their analytical approach by using it to compare the sequences of corresponding genome segments from 19 mammalian species, including human, horse, lemur, rat, rabbit, hedgehog and armadillo. Such comparisons among species across the mammalian evolutionary tree can yield insight into how mutational patterns have changed over evolutionary time.

They focused their analysis on a 1.7 million base pair DNA segment known as the "greater cystic fibrosis transmembrane conductance regulator region," which was sequenced in the 19 mammals by Eric Green and his colleagues at the National Human Genome Research Institute. To concentrate on the neutrally evolving DNA, Hwang and Phil Green excluded the genes from those segments and compared what was left.

According to Green, the comparison of context-dependent mutation in the segments across the species revealed that the CpG mutations, unlike other mutation types, accumulated in a regular clock-like fashion. The analysis also distinguished other sources of naturally occurring mutations and their variation due to biological and biochemical influences, and appears to offer some insight into factors such as generation time and population size that have varied in mammalian evolution.

Green concluded that by contributing to a better understanding of naturally occurring mutations, the technique would help in understanding both how genetic disease arises and how evolution has occurred.

A next step, he said, will be to extend the analysis to sites on the genome that are not evolving neutrally. This should help identify genomic regions that were not previously recognized to be of functional importance, said Green. Also, he said, such analyses could offer considerable insight into how patterns of natural selection have varied across different species in the course of evolution.

"A more complex model of the neutral process should start to pay for itself in exploring these phenomena, because you're frequently looking for relatively subtle effects," said Green.


TOPICS: Miscellaneous; Unclassified
KEYWORDS: crevolist; evolution; genetics; mutation; poofism
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1 posted on 12/29/2004 12:11:52 PM PST by beavus
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To: beavus
help biologists understand how mutation contributes to evolutionary change in mammals

They won't find out anything, because there is NO EVOLUTION!
2 posted on 12/29/2004 12:13:44 PM PST by The Teen Conservative
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To: The Teen Conservative
They won't find out anything, because there is NO EVOLUTION!

How do you know?

3 posted on 12/29/2004 12:16:14 PM PST by beavus
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To: The Teen Conservative
They won't find out anything, because there is NO EVOLUTION! Heh, there is at least micro-evolution, that is evolution of species within the same genus. Almost everyone even among Creationists acknowledges this. Might want to review some of the article on speciation. Good spirit though, just try and look at the facts honestly.
4 posted on 12/29/2004 12:26:10 PM PST by JFK_Lib
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To: JFK_Lib

There is no micro evolution. It is variation of a species, the name micro evolution was given to bolster belief of evolution. evolution as taught by Darwin has been proven not to exist, the fosil record doesn't support the gradual evolution of species. Neo Darwinism was the next step in proving evolution, this was small mutations over a shorter period of time, but once again the fosil record didn't back up this theory, so now we come to today, and the theory advanced is punctuated equilibrium. This theory states that species go unchanged for millions of years ( which is true) and the suddenly without warning mutate into and entire new species. This, the evolutionists say, is why the fosil record shows no sign of evolution. The problem with this theory is that, despite many years of experiments, no mutations have ever been found that benefit a species. Mutations, which are damage to DNA, are never beneficial and most times do damage to the animal and often cause death. They are never self propagating, in other words the mutation cannot pass on to the next generation. This has been proven, but evolutionists continue to ignore facts and don't let the lack of proof stand in the way of a good theory, they never have. They are much like lefties. All this I have stated here can be checked out if you want to do some reserch, however, I see no need to do it for you. It is all on the web if you care to look.


5 posted on 12/29/2004 12:36:55 PM PST by calex59
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To: calex59
Many problems here.
1 - "evolution as taught by Darwin has been proven not to exist, the fossil record doesn't support the gradual evolution of species" Really? look at horses or whales or many other animals. I guess if you want to say 'gradual' means 'fossils from every 10 years the the history of the animal' then right you are. Welcome to natural history. not everything is fossilized and all that is isn't found.
2 - you admit the world has been around for millions of years, but think life would stay exactly the same, despite ice ages and isolation. hard to believe.
3 - mutations are not always bad. This is not x-men or bad sci-fi. mutant doesn't mean six fingers or giant pulsing brain or the ability to fly (which would be nice). People with lots of hair have different genes that those without. Same idea, different results (hair, no hair). Neither one will kill you, unless there's an ice age and then... And of course a mutation would pass to the offspring. If it's in the genes, it's going to the kids. I can't chose to not pass bad eyes to my kids. They get them.
Lots of proof for evolution. None for competing theories
6 posted on 12/29/2004 1:03:28 PM PST by bencarter
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To: PatrickHenry

Here's another one for the list...


7 posted on 12/29/2004 1:17:08 PM PST by Dementon (Life's tough. Get a helmet.)
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To: calex59
There is no micro evolution. It is variation of a species, the name micro evolution was given to bolster belief of evolution.

Call it what you will, environment is observed to affect the gene pool. Evolutionary biologists study this, experiment with it, model it, theorize about it, lecture on it, give courses about it, write articles about it, and write textbooks about it. It is a major part of evolutionary science.

evolution as taught by Darwin has been proven not to exist, the fosil record doesn't support the gradual evolution of species.

How flat-earthish of you to say that. The gradual changes that ARE observed in the fossil record are today best explained by evolutionary theory.

Neo Darwinism was the next step in proving evolution, this was small mutations over a shorter period of time, but once again the fosil record didn't back up this theory, so now we come to today, and the theory advanced is punctuated equilibrium. This theory states that species go unchanged for millions of years ( which is true) and the suddenly without warning mutate into and entire new species. This, the evolutionists say, is why the fosil record shows no sign of evolution.

Evolutionists, of course, don't say that "the fosil record shows no sign of evolution". Just the opposite. Fossils are inherently just snapshots in time, that happen to occur under the right conditions for preservation. The fact that we can only observe snapshots of a continuum does not mean the continuum does not exist. Punctuated equilibrium is a theory only about the RATE of evolution. It means to explain why sometimes small and sometimes large changes are seen between those snapshots.

The problem with this theory is that, despite many years of experiments, no mutations have ever been found that benefit a species. Mutations, which are damage to DNA, are never beneficial and most times do damage to the animal and often cause death. They are never self propagating, in other words the mutation cannot pass on to the next generation. This has been proven,

Your zeal is only matched by your ignorance on this matter. Mutations in gametes do propagate, and this is seen even in humans. It is an accepted medical fact. You are also wrong that mutations usually cause damage to an animal. In fact, mutations are far more likely to not even be expressed. Finally beneficial mutations, even in humans, have been found.

It is all on the web if you care to look.

This is the only thing you managed to get right in your whole diatribe. I suggest you look at the evidence yourself and make up your own mind rather than just parroting the rantings of your cult. The evidence just screams "evolution!"

And what is it exactly that you are suggesting as a better theory to explain the fossil record and facts of modern biology? Punctuated poofism?

8 posted on 12/29/2004 1:21:16 PM PST by beavus
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To: VadeRetro; Junior; longshadow; RadioAstronomer; Doctor Stochastic; js1138; Shryke; RightWhale; ...
EvolutionPing
Not a list for the creationism side of the debate. See the list's description in my freeper homepage. Then FReepmail to be added/dropped.

9 posted on 12/29/2004 1:43:49 PM PST by PatrickHenry (The List-O-Links for evolution threads is at my freeper homepage.)
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To: beavus
And what is it exactly that you are suggesting as a better theory to explain the fossil record and facts of modern biology? Punctuated poofism?

Creationists may, here and there, bamboozle the idiot housewives who seem to predominate on school boards, but such "victories" are shabby indeed. Evolution is supported not only by fossil evidence and a study of comparative anatomy, which was available to Darwin (showing hierarchical groupings), but also by several independent lines of evidence that turned up later, which could have -- but didn't -- give results that are inconsistent with the TOE:

* genetics (the inheritability of mutations),
* comparative biochemistry, including DNA (showing genetic relationships among species),
* geology (the age of the earth),
* plate techtonics (continental drift that coincides with fossil evidence),
* physics (radiometric dating of fossils and rock strata),
* astronomy (the age of the solar system and universe), and
* other supporting lines of evidence (tree rings, ice cores, ocean-floor cores, etc.).
Only one "teaching" is inconsistent with all these independent lines of evidence -- creationism.
10 posted on 12/29/2004 1:49:30 PM PST by PatrickHenry (The List-O-Links for evolution threads is at my freeper homepage.)
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To: PatrickHenry
Only one "teaching" is inconsistent with all these independent lines of evidence -- creationism.

Not if you admit two governing principles:

(1) With God all things are possible, and
(2) God works in mysterious ways.

With those, anyone can claim anything they wish.

11 posted on 12/29/2004 1:54:58 PM PST by beavus
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To: calex59
Mutations, which are damage to DNA

Nope. Mutations are changes, and change is not necessarily damage. For example, when a mutation in bacteria produces a strain that is drug-resistant that is beneficial from the bacteria's point of view.

12 posted on 12/29/2004 1:56:59 PM PST by freespirited
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To: beavus

Well ... yes, of course. I should have mentioned that.


13 posted on 12/29/2004 2:06:01 PM PST by PatrickHenry (The List-O-Links for evolution threads is at my freeper homepage.)
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To: freespirited
Mutations are changes, and change is not necessarily damage.

Good point. "Damage" is a value statement, an editorial that says more than is needed in an objective analysis.

14 posted on 12/29/2004 2:08:24 PM PST by beavus
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To: PatrickHenry

That gives me an idea. I'll post nonsense on various threads with the sanctimonious claim that God told me. When asked to defend my nonsense, I'll reveal The Two Truths.


15 posted on 12/29/2004 2:12:33 PM PST by beavus
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To: beavus
I'll post nonsense on various threads with the sanctimonious claim that God told me.

Cute idea, but don't. The creationists do enough of that routinely. They wouldn't understand the satire.

16 posted on 12/29/2004 2:16:11 PM PST by PatrickHenry (The List-O-Links for evolution threads is at my freeper homepage.)
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To: PatrickHenry
They wouldn't understand the satire.

I suppose you're right.

17 posted on 12/29/2004 2:31:40 PM PST by beavus
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To: calex59
It is all on the web if you care to look.

Indeed it is, on lying creationist websites that never trouble to substantiate their claims, and which ignore the vast and rapidly growing volumes of physical evidence that support the theory of evolution as an explanation of the observed fact of evolution.

18 posted on 12/29/2004 2:37:29 PM PST by Thatcherite (Conservative and Biblical Literalist are not synonymous)
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To: PatrickHenry

Thanks for the ping!


19 posted on 12/29/2004 8:33:59 PM PST by Alamo-Girl
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To: The Teen Conservative

YEC AMEN - read again later


20 posted on 12/29/2004 9:08:29 PM PST by LiteKeeper (Secularization of America is happening)
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