Free Republic
Browse · Search
News/Activism
Topics · Post Article

Skip to comments.

Study Hints at How Genetic Mutations Led to Macroevolutionary Change
Scientific American ^ | Kate Wong

Posted on 02/07/2002 8:49:05 AM PST by realpatriot71

EVOLUTION
Study Hints at How Genetic Mutations Led to Macroevolutionary Change

brine shrimp
Image: Matthew Ronshaugen/UCSD

The fossil record contains numerous examples of dramatic evolutionary change in animals through time. Exactly how genetic alterations brought about these macroevolutionary changes, however, has proved difficult to ascertain. Now new research into the developmental biology of brine shrimp and fruit flies could throw light on the matter. According to a report published online today by the journal Nature, mutations in genes that guide embryonic development allowed insects to develop a radically different body plan from that of their crustacean-like ancestors some 400 million years ago.

The University of California, San Diego, team that conducted the research focused on so-called Hox genes, master switches that turn other genes on and off during the embryonic development of all animals, including humans. One of these Hox genes, known as Hbx, suppresses 100 percent of limb development in the thorax region of fruit flies, but only 15 percent in the brine shrimp Artemia (right). Modifications of Hbx, the investigators determined, would have allowed the many-limbed, crustacean-like ancient relatives of Artemia to lose their rear limbs, giving rise to the six-legged insects. "Before the evolution of insects, the Ubx protein didn't turn off genes required for leg formation," team member William McGinnis explains. "During the early evolution of insects, this gene and the protein it encoded changed so that they now turned off those genes required to make legs, essentially removing those legs from what would be the abdomen in insects."

In addition to shedding light on how major shifts in body design evolved, the new finding could help scientists better understand certain human diseases and deformities. "If you compare [Hbx] to many other related genes, you can see that they share certain regions in their sequences, which suggests that their function might be regulated like this gene," remarks lead study author Matthew Ronshaugen. "This may establish how, not only this gene, but relatives of this gene in many, many different organisms actually work." A number of these genes are involved in cancer and developmental abnormalities, he says, and "they may explain how some of these conditions came to be." ÑKate Wong

RELATED LINK:

"How Limbs Develop," by Robert D. Riddle and Clifford J. Tabin (Scientific American, February 1999), is available for purchase at the Scientific American Archive.


TOPICS: Miscellaneous
KEYWORDS: crevolist; evolution
Navigation: use the links below to view more comments.
first previous 1-2021-4041-6061-69 next last
To: ThinkLikeWaterAndReeds
Prior to the big bang, there must have been something to go BANG, and there must have been some mighty force to ignite that something that went bang.

This logic cannot be applied to first causes for the simple reason that you are merely pushing back the origins question. If God existed prior to the Big Bang, how did God originate?

The only honest answer is that no one knows. The same answer a scientist would give to the origin of existence.

41 posted on 02/07/2002 10:28:16 AM PST by js1138
[ Post Reply | Private Reply | To 25 | View Replies]

To: realpatriot71
When did you take intro bio?
42 posted on 02/07/2002 10:32:32 AM PST by tallhappy
[ Post Reply | Private Reply | To 39 | View Replies]

To: twigs
how long would it take, given the proper separation, for man to develop the physical differences we witness today.

I'll be honest. I don't know, but since I'm a believer in a recent creation I'd guess approximately 20,000-10,000 years.

43 posted on 02/07/2002 10:46:36 AM PST by realpatriot71
[ Post Reply | Private Reply | To 40 | View Replies]

To: tallhappy
I had my first undergrad bio class 5 years ago
44 posted on 02/07/2002 10:47:19 AM PST by realpatriot71
[ Post Reply | Private Reply | To 42 | View Replies]

To: js1138
As a Taoist, I believe that there is a force in the universe, and beyond, that is incomprehensable and eternal and attempts to quantify it is nonsensical. Everything issues from it and everything returns to it. This is the only "leap of faith" required in my belief and excludes total randomness.
45 posted on 02/07/2002 10:54:29 AM PST by ThinkLikeWaterAndReeds
[ Post Reply | Private Reply | To 41 | View Replies]

To: realpatriot71
Have you read Bryan Sykes' The Seven Daughters of Eve: The Science That Reveals Our Genetic Ancestry? He argues that genetic mutations of mitachondrial DNA would trace most--I think around 95%--of Europeans back to seven women, the oldest of which would have been 35,000-40,000 years ago. That's from memory, so I'm not certain about the exact years he postulates. He also assumes that all these women were descended from an Eve. I found the book fascinating, but I could not evaluate it properly because I just don't know enough about genetics. I also believe in a more recent creation, but I can't always reconcile the differences I read between competing theories.
46 posted on 02/07/2002 11:02:06 AM PST by twigs
[ Post Reply | Private Reply | To 43 | View Replies]

To: Sabertooth
Well said, but it's a little difficult for early 21st Century man to admit he doesn't know evrything.
47 posted on 02/07/2002 11:09:42 AM PST by colorado tanker
[ Post Reply | Private Reply | To 6 | View Replies]

To: ijcr
Did this not occur in Thalidomide children?

The deformities of the thalidomide children were the result of thalidomide's ability to block the formation of new blood vessel systems in the body. The body's ability to form blood vessel systems is vital during fetal development, because arms, legs, etc. require the development of their own individual blood vessel systems to develop properly. You can think of the stunted or, apparently, missing, in some cases, limbs of the thalidomide children as body systems which were not supplied with the necessary nourishment for their normal development.

Interestingly, thalidomide, along with other drugs which, similarly, obstruct the development of new blood vessel systems, are proving to be quite beneficial in the area of the cancer treatment. The body's capability to develop new blood vessel systems is only really needed when new body structures are being developed, and is rarely in evidence in the human body apart from fetal development, menstruation, and cancer. In order for cancers to go from being pin-prick sized groups of abberantly multiplying cells to life-threatening masses, they need to grow, and, thus, need to develop their own blood vessel systems to supply themselves with the nourishment required for growth.

If blood vessel system development is obstructed, cancers cannot grow to life-threatening size, and, thus, can be controlled. Thalidomide and similarly acting drugs are currently being tested to determine their effectiveness in fighting cancer growth in humans. The most effective dosages and schedules of treatments are currently being worked out. To date, the results are mixed.

48 posted on 02/07/2002 11:16:26 AM PST by Quester
[ Post Reply | Private Reply | To 8 | View Replies]

Comment #49 Removed by Moderator

Comment #50 Removed by Moderator

To: Quester
That hypothesis is questionable. Thalidomide caused the birth defects only during a certian early period of pregnancy.

It is more likely it specifically altered certain developmental pathways during that time of development at a transcriptional level.

It is surprising to me that no one has actually made the effort to determine exactly why it cause the birth defects it did.

51 posted on 02/07/2002 11:47:22 AM PST by tallhappy
[ Post Reply | Private Reply | To 48 | View Replies]

To: toddhisattva
"species" is a man-made concept

One of many. We each look at the same thing and see something different.


Example:
I look at OBL and see a man caught up in his reflection of the outside world, a man of war. Others look at OBL and see a man of God, with no concern for the outer world.

I look at Musharaff of Pakistan and see a man of God, a master of his own soul. Others look at Musharaff and see a warrior on the physical earth and a conniving politican to boot.

Different species, and we don't even agree on taxonomy.

52 posted on 02/07/2002 11:54:48 AM PST by RightWhale
[ Post Reply | Private Reply | To 50 | View Replies]

To: tallhappy
That hypothesis is questionable.

This is not a hypothesis. It has been tested and verified.

It is surprising to me that no one has actually made the effort to determine exactly why it cause the birth defects it did.

Did you really believe that noone had done this?

From the BBC News Online January 25, 2001

The controversial drug Thalidomide is being used to help treat the most deadly form of lung cancer.

The drug became notorious in the 1960s when it was prescribed to pregnant women to ease morning sickness.

It was found to cause severe birth defects by limiting the blood flow to developing limbs. Many children were born limbless or with severely shortened limbs. Now scientists hope to use the blood limiting properties to help small cell lung cancer patients by starving the blood supply to tumors.

Researchers are already using Thalidomide in drugs trials to treat Kaposi's sarcoma (a type of cancer involving blood vessels in the skin) and brain cancer.

53 posted on 02/07/2002 12:43:14 PM PST by Quester
[ Post Reply | Private Reply | To 51 | View Replies]

To: crevo_list
Bump.
54 posted on 02/07/2002 12:58:59 PM PST by Junior
[ Post Reply | Private Reply | To 1 | View Replies]

To: Quester
See the review I cited earlier.
55 posted on 02/07/2002 1:21:44 PM PST by tallhappy
[ Post Reply | Private Reply | To 53 | View Replies]

To: Quester
Questor, here is the web site for Annual Review of Pharmagology and Toxiology http://pharmtox.AnnualReviews.org/

The article is MOLECULAR BASIS OF ENVIRONMENTALLY INDUCED BIRTH DEFECTS Annu. Rev. Pharmacol. Toxicol. , Vol. 42: 181-208

from their 2002 issue.

Here is their paragraph on Thalidomide:

PROPOSED MOLECULAR MECHANISMS OF KNOWN TERATOGENS

Thalidomide

The literature on birth defects associated with in utero exposure to thalidomide contains over two thousand citations, in keeping with the fact that this is the most infamous of all pharmaceutical teratogens (96). In spite of intensive investigation over the past forty years, the mechanism by which thalidomide disrupts normal embryogenesis remains a topic of considerable controversy. Perhaps as a result of its checkered history, a large number of hypotheses have been put forward over the years in an attempt to explain its teratogenic mechanism of action. Twenty-four different hypotheses were reviewed by Stephens, who found that 13 of the hypotheses were fundamentally incorrect (97). Of the remaining 11 hypotheses, some were supported by experimental data, albeit not sufficiently conclusive or convincing. Several other hypotheses remain to be adequately tested. The hypotheses could generally be classified into those proposing that thalidomide affects DNA replication or transcription, its impact on the synthesis and/or function of growth factors or integrins, and finally, thalidomide's effects on angiogenesis, chondrogenesis, cell death, or cellular injury.

More recently, Stephens and coworkers (96, 98) proposed a model of the thalidomide embryopathy that neatly unifies previous hypotheses and provides a biologically sensible model system that accounts for the existing biochemical data, as well as explains the molecular specificity of this teratogen. In this model system, the insulin-like growth factor-1 (IGF-1) and fibroblast growth factor-2 (FGF-2) proteins work cooperatively in order to stimulate the production of alpha-5 and beta-3 integrin subunits. These integrin subunits have been previously demonstrated to function as angiogenesis factors, promoting vascularization in the developing limb bud, as well as select embryonic structures (99, 100, 101). The IGF-I and FGF-2 genes are transcriptionally regulated by the transcription factor Sp1. Sp1 binds guanine-rich GC box elements (GGGCGG) located in the promoter regions of select target genes. In this case, the genes are IGF-I and FGF-2, as well as their receptors. Stephens & Fillmore (96) propose that binding of thalidomide to the promoter prevents subsequent Sp1 binding, thereby downregulating the transcription of the two target genes. Even a subtle downregulation of critically important genes can adversely affect the developmental processes involved in embryogenesis.

Data in support of this hypothesis include a relatively robust literature that demonstrates that IGF-I can stimulate chondrogenesis and limb development (102, 103, 104). More recently, it has also been demonstrated that thalidomide can inhibit IGF-I stimulation of limb development under experimental conditions (102). The IGF-I gene promoter lacks both TATA and CCAAT boxes and is highly guanine-rich, containing several Sp1 binding sites (105). This makes the IGF-1 gene particularly vulnerable to intercalation by thalidomide. The drug is able to oxidize DNA at position 8, which faces the major groove of the DNA molecule and may serve to facilitate intercalation at those sites. Similarly, FGFs also play significant roles in both limb development (106, 107, 108) and angiogenesis (109, 110, 111). Like the IGF-I gene, there are no TATA or CCAAT boxes on the FGF-2 promoter, but there are multiple Sp1 and early growth response protein (Egr-1) binding sites. The FGF-2 gene, then, represents another potential target of thalidomide interference in limb development.

The question of specificity of teratogenic effects can also be explained by thalidomide's proposed interaction with specific gene promoters. Clearly, the key morphological structures affected by in utero exposure to thalidomide are the limbs, ears, and eyes. As such, it is thought that the intercalation of thalidomide at guanine-rich sites in DNA is having its greatest impact at the promoter regions of genes critical to the development of these structures. Perhaps less than 9% of all gene promoters have neither a TATA nor a CCAAT box. These genes depend upon promoters with one or more GGGCGG sequences (112). Stephens & Fillmore propose that thalidomide intercalates into promoter regions that have long stretches of poly-G regions, as these are biophysically favorable sites for thalidomide binding (96). The specificity of thalidomide targets is further enhanced by the fact that since most GC regions in the Sp1 binding sites are constitutive, they would be unlikely to tolerate regulation during embryonic development (96).

Here are the Stephen's references:

Stephens TD, Fillmore BJ. 2000. Hypothesis: thalidomide embryopathy-proposed mechanism of action. Teratology 61:189–95

Stephens TD. 1988. Proposed mechanisms of action in thalidomide embryopathy. Teratology 38:229–39

Stephens TD, Bunde CJ, Fillmore BJ. 2000. Mechanism of action in thalidomide teratogenesis. Biochem. Pharmacol. 59:1489–99

Have a look.

56 posted on 02/07/2002 1:41:27 PM PST by tallhappy
[ Post Reply | Private Reply | To 53 | View Replies]

To: DaveyB
All together now ..."600 billion years ...yada yada yada ..."

That would be about 4 billion years on this planet.

57 posted on 02/07/2002 1:43:07 PM PST by <1/1,000,000th%
[ Post Reply | Private Reply | To 9 | View Replies]

To: tallhappy
Realpatriot71 is using the definition for the biological species concept. This is the definition most often in use, today. There is a typological way of looking at species, by degree of difference between two populations, but it does not make a determination about mating success.
58 posted on 02/07/2002 2:40:44 PM PST by Nebullis
[ Post Reply | Private Reply | To 42 | View Replies]

To: ijcr
Did this not occur in Thalidomide children?

Please don't confuse teratogenic effects, external effects which cause damage during development, with germ-line mutations.

59 posted on 02/07/2002 2:44:10 PM PST by Nebullis
[ Post Reply | Private Reply | To 8 | View Replies]

To: <1/1,000,000th%
I thought it was 3.6 billion years!! Those last 400 million must have snuck up on me out of nowhere!
60 posted on 02/07/2002 2:59:01 PM PST by realpatriot71
[ Post Reply | Private Reply | To 57 | View Replies]


Navigation: use the links below to view more comments.
first previous 1-2021-4041-6061-69 next last

Disclaimer: Opinions posted on Free Republic are those of the individual posters and do not necessarily represent the opinion of Free Republic or its management. All materials posted herein are protected by copyright law and the exemption for fair use of copyrighted works.

Free Republic
Browse · Search
News/Activism
Topics · Post Article

FreeRepublic, LLC, PO BOX 9771, FRESNO, CA 93794
FreeRepublic.com is powered by software copyright 2000-2008 John Robinson