Blinn

Clearly not, but I'm betting he's pretty familiar with <a href="http://www.drbronner.com/story.html" target="_blank">Dr. Bronner's musings</a>.

Vanderzyden, it’s not a “short” paper but rather a succinct one. Coragyps is quite correct. I once had a wildlife bio. techniques class where aside from learning how to radio-track animals and sample tree density in a forest, we learned how to “write” a proper, scientific paper. Our own assigned papers were to be a maximum of 3 pages, including literature cited!

</strong>

Vanderzyden, the first part of a scientific paper is generally known as an introduction. This is where the researcher(s) present their hypothesis, and succinctly state what information is already known (or not known) that relates to the question they are trying to answer. The researchers are making a statement that existing information points to the apparent fusion being either centromeric or telomeric in nature. The research that they present in this paper conclusively demonstrates it to be a telomeric fusion. The paper itself excludes a centromeric fusion, hence the title!

I'm tempted to clear up some more of your misunderstandings but I'm sure Scigirl can do a much better job of it than I could.

[ September 02, 2002: Message edited by: Zetek ]</p>

Happy Wonderer

And of course, that was another nicely crafted red herring by Vanderzyn. How exactly would it affect the original argument if the fusion had been centromeric or telomeric in nature? We have a chromosone that appears to be the fusion of two chromosones that chimps, gorillas, and orangs have. The answer "but it is a centromic rather than a telomeric fusion" counters the conclusion that we share a common ancestor in what way?

HW

[ September 02, 2002: Message edited by: Happy Wonderer ]</p>

scigirl

Vander (or anyone),

Could you do me a favor and tell me the author name, volume, year and page number of that PNAS article? I am having trouble getting it to download.

Thanks,

scigirl

Jesus Tap-Dancin' Christ

Volume 88, PP 9051-9055
Origin of Human Chromosome 2: An ancestral Telomere-Telomre Fusion
JW IJdo, A Baldini, D C Wards, S T Reeders, and R A Wells.

Hope that helps scigirl.

[ September 03, 2002: Message edited by: Jesus Christ ]</p>

Blinn

Scigirl,

I'm not sure if it will help you open it or not, but I just e-mailed the paper to you as a pdf file.

Zetek

-returned to me... too big for hotmail.com

[ September 03, 2002: Message edited by: Zetek ]</p>

scigirl

Zetek,

Thanks for the email.

I actually got the article today at the library. Like - a real library! UCHSC has a pretty big one, and it's organized in alphabetical order, unlike my last university (library of congress is a nightmare )

Anyway, before I delve into specifics on the telomere article, I want to briefly explain how a journal article works.

There are several parts to a primary research article.

Title: A specific description of what the researchers did or found. The more specific the title, the better (sometimes they can be very long).

Abstract: A paragraph summary that briefly outlines the methods, results and conclusion of the study.

Introduction: These first few paragraphs of an article introduce the topic by explaining a couple of things: What is the current state of research on topic X? What are the researchers asking about topic X, and how are they asking it? Also, often this part will explain why anyone cares about the subject. Papers are always built on previous papers, so intros will usually contain statements like, "previous research suggests X and Y, therefore, we propose Z."

In other words, this is where the questions are asked (they will be answered later in the article). These are the statements Vanderzyden was hung up on, and hopefully this clears up his confusion.

Methods: A detailed description of what the researchers did, so that someone could repeat, or verify, the results.

Results: The data, or meat, of the paper, with brief explanations of what the data mean. Usually pictures or graphs are found here as well. Data can be qualitative, semi-quantitative, or qualitative. Many papers have a combo of all three.

Discussion: Probably the most important, yet the least understood, part of a research paper. Here, the authors attempt to answer their question (i.e. was their hypothesis correct) using their data. Sometimes, the hypothesis is refuted, sometimes it is supported, or sometimes it is a combination of both.

Several things happen in the discussion:
1. The researcher must put their data into context. Does it fit with other data that has been published on the subject? If so, how? If not, why not? For instance, maybe their data was in mice, and the other *contradictory* data was in frogs.

2. The researcher speculates about ideas or mechanisms. This is the 'brainstorming' section of the paper, and it is what separates science from simple data collection and reporting. How could these results cure cancer, or explain black holes, or figure out evolution? Other researchers read the discussion and could possibly be inspired.

3. The researcher talks about what to do next. You can usually tell what the researcher is currently working on, simply by reading the discussion from their last published paper. And this is an important step, since a lot of studies raise more questions then they answer!

Now when a non-scientist tries to read a research paper, they tend to make one of two mistakes:
A. Become confused by all the "putative" words in the introduction, because they don't understand the basic set-up of a paper
or
B. Assume that the speculations in the discussions are "gospel" truth, and if those speculations are wrong, than the whole paper must be wrong.

Now let's delve into the paper in more detail in my next post.

scigirl

A disussion of the following paper from PNAS:

<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=192436 7&dopt=Abstract" target="_blank">Proc Natl Acad Sci U S A 1991 Oct 15;88(20):9051-5</a>

First I'll make note of the journal. PNAS is considered a leading journal, and most articles that get published here (as in Nature or Science ) are groundbreaking in some fashion. The downside of these papers is they are fairly short - and they assume the reader knows a lot. So they can be tough to comprehend.

The title of the article is "Origin of human chromosome 2: an ancestral telomere-telomere fusion."

Here is their abstract:
The introduction of their paper states the following:
1. Scientists had previously found similarities in the human and ape chromosomes, and had some preliminary evidence that a fusion had occured. It still wasn't clear, however, if it was a centromeric or a telomeric fusion.

2. Scientists already knew that the ends of human chromosomes had these head-to-tail tandem arrays of a specific base pair sequence (TTAGGG) or a slight variation. They also knew that in a subset of chromosomes, additional repetitive sequences were found adjacent to these sequences. These are called flanking, or pretelomeric, sequences.

3. Therefore the researchers decided to use what they knew about the telomeric and sub-telomeric sequences to clarify if indeed a fusion had taken place, and what type of fusion it was.

Methods: I won't go into too much detail, but here's the jist of what they did:

1. They had a library of chromosomes in pieces of DNA called 'cosmids.' Someone else (probably a grad student ) had chopped up individual human chromosomes and put them into cosmids, and kept track of what cosmids had what parts of the chromosomes. So they designed two probes, one that recognized the subtelomeric region, and one that saw the TTAGGG repeats. They then searched, or "screened the library" using the probes. The researchers found 2 cosmids that produced a "hit" to both probes, which were in th cosmids corresponding to chromosome 2.

2. Then the researchers did some restriction mapping and DNA sequencing to determine where these repeats were in the chromosome.

4. To confirm their results, they obtained blood from 6 different humans and prepared their chromosomes for analysis. Then they probed these 'real' chromosomes for the same telomeric and sub-telomeric sequences.

Results:

1. "Identification and Characterization of Genomic Cosmids Mapping to Band 2q13"
The cosmids that tested positive with their probe were analyzed to figure out what chromosome was binding to the probe. They localized, with two individual cosmids, these sequences to the band 2q13 (just the way that areas are localized to a chromosome, like a grid on a map).

After mapping and sequencing these regions in the chromosome, the researchers found something very interesting: The telomeres were inverted. See my picture from page 6 to visualize this once again. Also the pre-telomeric sequences were inverted.

Now at this point, there is still another possibility, other than fusion. Read on:
To distinguish between these possibilities, the researchers studied two other clones which come from the telomeric repeat portion of the chromosome but are missing the inverted-repeat region.
So that possibility is elimated, strengthening the fusion case even more.

But the researchers still want to make sure their conclusions are solid, so they do yet another confirmation.

2. Confirmation of the Subtelomeric Origin of the Sequences Flanking the Telomeric Array.
This is the experiment described in the methods that involved probing the chromosomes of 6 human subjects.
As always happens when you test your theory in the real world, it is more complex and variable:
Discussion. Their definitive conclusions:
So that question that Vander had a problem with and quoted here...
...was the very question that the paper exactly addressed and answered!

Oh and Vanderzyden also asked, "Just what does this mean, anyway? Characteristic of what? Well, we are not told."

Well like I said earlier, you read a PNAS paper, and you run the risk of being confused, unless you are a scientist in that field. What they mean, is, that these sequences are a characterisic of chromosomes that are often found near telomeres. The "subtelomeric regions" that I drew in with arrows are the flanking sequences. Hope that helps.

Now, what else does the discussion say?

1. It reconciles the data with what is known:
Since I have not seen any peer-reviewed reputable papers completely denouncing the "phylogenetic data" that Vanderzyden doesn't like, I will stick with the scientist's conclusions for now. (Incidentally I have done some phylogenetic analysis, and I can tell you that while the methods are scientifically and mathmatically sound, they are occasionally used incorrectly in the literature).
The authors then make the following logical inference, based on what they know about chromosomes:
They also make this observation:
To me, unpublished data is weaker than published data. I'm assuming here that AB is one of the authors, A Baldini. Did this data eventually get published? <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=844446 4&dopt=Abstract" target="_blank">Yes it did.</a>
So Vander's problem with the data being "unpublished" is no longer a valid concern.

2. The authors discuss at length whether fusions are even possible, and provide numerous references and examples that yes, indeed they are.
Then the authors go on to talk about more tests then can do (and probably already did - like the centromere study).

Let's summarize what the researchers found:
1. Inverted telomeric sequences, and their corresponding subtelomeric (flanking) sequences in inverted order, as would be predicted by a telomere to telomere fusion.
2. The data cannot be explained by a small duplication and inversion, based on the nearby sequences of the chromosome.
3. The data was confirmed in 6 humans, and fits with what was previously known about the chromosomes.

scigirl

[ September 03, 2002: Message edited by: scigirl ]</p>

Stephen T-B

Reading this thread puts in me in mind of what it might be like listening to a discussion between a bunch of meteorologists who have discovered that the winds are caused by differences in atmospheric pressure, and a guy who objects to that explanation because his holy scriptures teach that they’re caused by the clouds being pushed around the sky by the finger of god.
It is worthwhile, from time to time, to reflect on where Mr V. is coming from. He’ll put me right if I’m wrong, but I suppose he believes in the Genesis account of Creation, meaning he objects to naturalistic explanations of observable phenomena because he prefers a Biblical one. He believes, for instance, that a god created light, and Life, BEFORE he put the sun in the sky.
Instead of scientists having to justify to him their naturalistic explanations, should he not be explaining to them his Scriptural ones? Or would that be pointless because at every juncture where no reasonable, rational explanation can be provided, he only has to say “It was a miracle wrought by God.”
Mr V does not like scientists - or didn’t when he first came here - because they are not content to settle for that simplistic, fatuous, explains-nothing “explanation.”
They are, in effect, applying to their work a principle we learn as children, ie, that if a god is involved in anything at all, it’s certainly not in a way which impacts physically upon the physical universe. A child, for instance, will discover sooner or later that it isn’t god that puts milk in the milk jug or bread on the table or makes the automobile move down the road. Gradually, as we grow up (most of us, anyway), the scope for mythical, mystical yet satisfactory explanations of all that we physically experience in our lives becomes drastically reduced.
And this same process has been taking place over the last 450 years or so in European cultures in which the power of religious orthodoxy has progressively diminished.
And just as well, for the very same unfettered urge for exploration which lead Charles Darwin to his proposition of a natural process leading towards modern life-forms has also led to an understanding of what causes pestilence, plague and famine.
Mr V. as I have remarked before, cannot cherry pick in terms of what is or is not permissible for our curiosity to examine. If Darwin had not been allowed to examine the origins of life, would Pasteur have been allowed to examine the role of bacteria in causing human disease? And Mr V. remember, if you will, that while men’s minds were shackled by religious dogmas - the same dogmas you still espouse - disease was a manifestation of God’s wrath and vengeance. And while that belief held sway, what prospect was there for any advance in man’s knowledge of how the world really works?

Peez

A chromosome is made up of two sister chromatids only after the DNA has been replicated (in preparation for cell division). The poster seems to be confused about sister chromatids vs homologous chromosomes. Humans have 23 pairs of chromosomes (46 chromosomes), and these pairs are not identical to each other, nor are they attached together. After DNA replication (and before cell division) there are therefore 92 chromatids. The fusion of two chromosomes in a germinal cell (spermatogonium or oogonium) of the testes or ovaries that started with 48 chromosomes would result in a cell with 47 chromosomes (22 pairs and one group with two smaller chromosomes "paired" with one larger chromosome). Such a cell would function normally: essentially like one with 24 pairs of chromosomes (with two chromosomes tied together).

Of course, the fusion might happen during or after meiosis (e.g. in a sperm or egg), that would start with 24 chromosomes (not in pairs), and end up with 23 chromosomes. If the chromosomes are joined, then after DNA replication the chromatids formed would be joined as well (i.e. there would be two sister chromatids). Perhaps there were two centromeres at one time. What is the problem? What chromatid? Chromatids are just copies of the chromosome after DNA replication. Did he think that the scientists missed that? I am not familiar with the current understanding of the process involved, but it is not hard to imagine that some material was lost at the joining. Shouldn't that be "(c)"? Why?

Peez

Oolon Colluphid

Oops... sorry Peez!

Not my day...

Oolon