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Monday, March 26, 2007

Internet Connection Speeds

 
Here are the results of a test for internet connection speed from InternetFrog.com. This is the speed I get at the university.

Now, here's some questions for all you technical experts out there. The download speed varies from a low of 2 Mbps to a high of close to 9Mbps. Why? Does anyone have faster connections on a regular basis?

The upload speed varies from a low of about 150 Kbps to a high of 1.7 Mbps. Why? And why is the upload speed so much slower than the download speed? Does that depend on the speed of my processor?



[Hat Tip: Kevin Black]

Happy 66th Birthday Richard Dawkins

 
Today is Richard Dawkins' birthday [RichardDawkins.net]. Go [here] to enter your own birthday message.

I may disagree with Dawkins on some parts of evolutionary theory but I think he's done a wonderful job of focusing attention on evolution as a scientific fact. I'm also a strong supporter of his attacks on superstition and support for rationality (e.g., The God Delusion).

Dawkins is just one of many intelligent men and women whose brains did not shut down when they turned 50 or 60. We need to point this out because there are, unfortunately, too many people who think that you can only make a contribution to science when you're under 40.

Monday's Molecule #19

 
Name this molecule. You must be specific but we don't need the full correct scientific name. (If you know it then please post it.)

As usual, there's a connection between Monday's molecule and this Wednesday's Nobel Laureate. This one's easy once you know the molecule and make the connection. There'll be a few extra bonus points for guessing Wednesday's Nobel Laureate(s).

Comments will be blocked for 24 hours. Comments are now open.

Sunday, March 25, 2007

RNA Polymerase Genes in the Human Genome

 
The structure of yeast RNA polymerase II was solved by Roger Kornberg [Nobel Laureate: Roger Kornberg]. There are many different polypeptide subunits labelled Rpb1 to Rpb12 in the nomenclature used by yeast workers. The mammalian enzyme is very similar. Most of the same subunits are present but they have different names.

The core of RNA polymerase is composed of two very large subunits called Rpb1 and Rpb2 in yeast. In mammals they are called subunits A (220 KDa) and B (140 KDa). These subunits are homologous to the β and β′ subunits in bacterial RNA polymerases. The genes for these polypeptides in humans are called POLR2A and POLR2B. They are located on chromosomes 17p13.1 and 4q12 respectively.

The Online Mendelian Inheritance in Man database has entries for both genes but there are no genetic diseases associated with mutations in either gene [OMIM POLR2A and OMIM POLR2B]. This should not be a surprise since it is rare for genetic diseases to be associated with important essential genes.

Recall that mammals have four different RNA polymerases [Eukaryotic RNA Polymerases]. Both RNA polymerase I and RNA polymerase III have homologous large A and B subunits. The genes for these polypeptides are called POLR1A (194 KDa, chromosome 2p11.2), POLR1B (128 KDa, chromosome 2q13), POLR3A (155 KDa, chromosome 10q22-q23), and POLR3B (~120 KDa, chromosome 12q23.3). As is the case with the large subunits of RNA polymerase II, none of these genes are associated with metabolic diseases because they are essential, important housekeeping genes.

These genes make up a typical eukaryotic gene family. It's important to remember that a gene family refers to homologous genes within the same genome and not to a group of homologous genes from different species. Gene families arise from gene duplication events.

The "A" genes evolved from a common ancestral RNA polymerase β gene several billion years ago and the "B" genes evolved from an ancestral β′ gene. The β and β′ genes, in turn, evolved from a common ancestor near the time life began about 3.5 billion years ago.

The "A" and "B" genes have evolved independently by divergence. In such cases the family members are often on different chromosomes and the intron-exon organization of each member is very different in spite of the fact that the genes are still closely related in amino acid sequence.

In addition to the "A" and "B" genes for each RNA polymerase, there are genes for three different subunits of RNA polymerase I (POL1C, POL1D, POL1E), 12 different subunits of RNA polymerase II (SURB7 and POL2C - POL2L), and 9 different subunits of RNA polymerase III. There are also dozens of genes for the general transcription factors required for initiation, elongation, and termination. Altogether, there are at least 80 different genes required for transcription and that's not counting any gene-specific regulatory genes.

The fourth RNA polymerase in humans is the mitochondrial version. Its gene is POLRMT located on chromosome 19p13.3. The large subunit of the mitochondrial RNA polymerase is only distantly related to the others. There are no metabolic defects associated with mutations in POLRMT [OMIM POLRMT].

Happy Birthday Elton John!

 
Elton John is 6o years old today.










The Salem Conjecture

 
The Salem Conjecture was popularized by Bruce Salem on the newsgroup talk.origins. It dates to before my time on that newsgroup (1990) and I haven't been able to find archives to research the exact origin. The conjecture was explained by Bruce on numerous occasions, here's a statement from Sept, 5, 1996.
My position is not that most creationists are engineers or even that engineering predisposes one to Creationism. In fact, most engineers are not Creationists and more well-educated people are less predisposed to Creationism, the points the statistics in the study bear out. My position was that of those Creationists who presented themselves with professional credentials, or with training that they wished to represent as giving them competence to be critics of Evolution while offering Creationism as the alternative, a significant number turned out to be engineers.
This is the so-called "soft" version of the conjecture. The "hard" version is that there is something about being an engineer that leads one to become a creationist. That's not what Bruce said,
For a long the so-called "soft" hypothesis is the one I have been putting forth, not the one earlier attributed to me. I have also further qualified it by saying numerous times that religious belief was the most significant factor. The reason I prefer to call my idea a "conjecture" is that I have had only anecdotal data to support it.
The Salem Hypothesis has its own entry on Wikipedia [Salem Hypothesis]. Both versions of the Salem Conjecture are listed there. The talk.origins Jargon File is incorrect because it only lists the hard version and attributes it to Bruce Salem.

We all know that scientists overwhelmingly reject creationism so it doesn't come as a surprise that there are so few scientists in the creationists movement. Ironically, the creationists long for scientific validity while, at the same time, they attack all the basic principles of science. The few so-called scientists who subscribe to superstition get very prominent play among the creationists.

Engineers are not scientists and they did not have much scientific training in school. They are technologists (i.e., engineers) and that's not the same thing. I don't think engineers spend much time studying evolutionary theory in university. (It's probably too difficult for them.)

Among the general public the distinction between scientists and technologists is lost so whenever an engineer comes out in favor of superstition (s)he is counted as a scientist. This is what the Salem Conjecture says. Whenever you see a common run-of-the-mill creationist who claims to have scientific knowledge, chances are they're an engineer and not a scientist.

Here's how Bruce explained it on talk.origins on May 10, 1996 in response to an engineer who was objecting to the conjecture.
By your own admission you are running the risk of becoming yet another data point for something called the "Salem Hypothesis" or "Salem Conjecture" in which I noticed some time ago the number of people publically supporting Creationism whether in Creationist publications or this group claiming to be "scientists" were mostly engineers. Most of them had little knowledge of the scientific disciplines that relate to the scientific acceptance of evolution and an old earth. Many people have noticed subsequently that while engineers as a group seem more inclined as a majority to believe Darwin, those with a background in certain religions and those concerned with intelligent design seemed predisposed to accept
Creationism or the arguments that support it.
This morning Larry Faraman, the author of the blog I'm From Missouri, posted this message [The Salem Hypothesis].
I have been aware for a long time that engineers have an especially strong tendency to be skeptical of Darwinism, but I just now learned that this tendency has a name: the "Salem hypothesis." I am especially interested in this tendency because I am an engineer myself ....

I feel that the reason why we engineers tend to be skeptical of Darwinism is that we are a logical, practical, no bullshit, cut the malarkey, "I'm from Missouri," "show me" kind of people.
The irony is palpable. Mr. Faraman, an engineer, is skeptical of evolutionary biology and, by implication, most of the rest of science. On the other hand, he's not the least bit skeptical of creationism. Another solid data point for the Salem Conjecture. In this case, it's the "hard" version that Mr. Faraman is supporting. He claims that training in technology predisposes one to believe in superstitious nonsense. Maybe he's right. I look forward to hearing from other engineers on this point.

BTW, Missouri must be a very strange state. These days when someone begins a conversation with "I'm from Missouri" it's usually following by something irrational.

Saturday, March 24, 2007

Dennis Kucinich on Universal Health Care

 
This is why I would vote for Dennis Kucinich ... if only I could vote. Why don't you vote for him?



[Hat Tip: Corpus Callosum]

Gene Genie #3

 
Hsien Hsien Lei has just posted Gene Genie #3 at Genetics and Health. There are >26,000 genes in the human genome and we hope to cover them in a finite amount of time. At this rate we'll be done sometime in the Spring of 2207! Let's pick up the pace, fellow bloggers.

The next Gene Genie (#4) will be hosted right here on Sandwalk. Send me your articles by email or submit them at blogcarnival [gene genie]. You ain't never had a friend like Gene Genie!

Summary of Genes on Human Chromosomes

 
I've prepared a table of the number and types of gene on each human chromosome based on the data at the Ensembl site managed by the Wellcome Trust Sanger Institute in Cambridge UK.

The total number of genes comes to 26,290.

The different categories of gene are:

Known: The "known" protein-encoding genes are those for which there is solid full-length cDNA evidence that they are actually expressed.

Novel: The "novel" class is reserved for genes that are predicted but lack confirming evidence.

miRNA: Micro RNAs are short single-stranded RNAs that are thought to play a role in regulating gene expression.

snRNA: Small nuclear RNAs are required for a number of cellular processes such as RNA processing. Those required for splicing associate with proteins in the nucleus to form small nuclear ribonuleoprotein particles or "snurps."

rRNA: Ribosomal RNA forms the core of the ribosome.

snoRNA: Small nucleolar RNAs are required for proper processing of ribosomal RNA. The are located in the nucleolar region of the nucleus because that's where ribosomal RNA is made.

other RNA: The "other" category includes transfer RNA (tRNA) and some specialized RNAs such as 7SL RNA and P1 RNA.
Chr. Size (kb)Protein
known
Protein
novel
Pseudo-
genes
miRNArRNAsnRNAsnoRNAother
RNA
    Total
    Genes
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
X
Y
247,249,719
242,951,149
199,501,827
191,273,063
180,857,866
170,899,992
158,821,424
146,274,826
140,273,252
135,374,737
134,452,384
132,349,534
114,142,980
106,368,585
100,338,915
88,827,254
78,774,742
76,117,153
63,811,651
62,435,964
46,944,323
49,691,432
154,913,754
57,772,954

2,146
1,375
1,111
828
922
1,103
984
736
921
819
1,390
1,088
358
661
657
915
1,232
293
1,428
612
271
509
878
86
54
84
47
59
63
29
68
32
38
35
52
51
10
28
65
49
60
20
49
15
23
26
37
27

159
40
45
32
23
81
48
19
66
52
61
38
41
25
34
25
56
8
45
29
9
39
80
2

43
23
24
21
19
17
31
17
26
16
19
21
14
51
15
14
32
5
71
16
7
15
58
6

42
24
21
13
22
16
14
14
11
17
19
15
9
14
6
13
10
42
6
8
10
2
19
6

178
116
89
81
74
82
64
61
43
64
51
77
29
42
43
39
47
12
14
32
5
18
64
14

60
37
30
16
18
25
27
21
15
8
40
21
12
56
95
14
29
12
12
16
5
11
25
3

93
74
66
58
67
56
62
39
47
42
47
65
34
38
35
31
52
21
18
34
6
20
48
2

2,616
1,733
1,388
1,076
1,185
1,328
1,250
920
1,101
1,001
1,618
1,338
466
890
916
1,075
1,462
401
1,598
733
325
601
1,129
140

Daisy, the Canada Goose

 
From KARE 11 News in Minneapolis, St. Paul, Minnesota (USA) [Daisy the Goose]. Why would evolution favor behaviors where a beagle, a Canada goose, and a human could get along in a boat? The video on the TV station's website is much, much better than the YouTube video. It's worth watching.

PZ's Hooked a Live One!

 
Hop on over to Pharyngula where PZ Myers is pointing out the deficiencies of an IDiot school teacher in Colorado [What's the matter with Colorado?].

This guy, Ken Poppe, has actually written a book exposing his ignorance. Look at the cover—that's supposed to be DNA but the structure is so wrong it makes you wonder if Poppe knows anything about science at all.

But here's the fun part. Ken Poppe has popped into Pharyngula to comment on PZ's post. Poppe's first comment is "I'm not afraid of your witchhunt. Bring it on, secularists. Bring it on." It goes downhill from there.

Friday, March 23, 2007

How Many Genes Do We Have?

 
The number of genes in the human genome flutuates on a monthly basis as the genome annotators add new genes and remove false positives. It's an ongoing process that's not likely to be complete in the near future.

The original draft sequences of the human genome had between 25,000 and 30,000 genes but these numbers were not reliable since they were based entirely on computer predictions. The programs were still in the testing stage for complex genomes when they were used in 2001. They are much better now but it really takes human intevention to assess whether a prediction is correct or not. The annotation process is tedious.

The latest summary from NCBI is based on the Oct. 17, 2006 genome assembly [NCBI Reference Assembly]. It lists 28,961 genes for the public genome and 26,245 for the private Celera assembly.

The Ensembl site has better data because the curation seems to be more rigorous. It lists 26,720 genes of which 3,994 have RNA products (mainly ribosomal RNA, tRNAs, and snoRNAs) [Ensembl Homo sapiens]. This is not much different than the NCBI number. It looks like the total number of genes is stabilizing at 27,000 total genes and about 23,000 protein encoding genes.

Carl Zimmer recently posted an article about the number of genes in the human genome [You Don't Miss Those 8,000 Genes, Do You?]. He referred to the PANTHER database where they quote 25,431 genes on their current website [PANTHER pie chart]. This differs considerably from the 18,308 genes shown in Zimmer's original article at this site [PANTHER filtered NP]. The difference is due to filtering the total number of genes (25,431) by showing only those that have a RefSeq entry in the Entrez database. This is an underestimate since not all genes have been assigned a RefSeq entry, particularly those that produce an RNA product rather than a protein.

[Thanks to Scientia Natura for the cartoon]

Your Hotel Key Card Contains Personal Information and Credit Card Numbers

 
Friday's Urband Legend: FALSE

I received this warning in an email message from a friend.
Ever wonder what is on your magnetic key card?
Answer:
a. Customer's name
b. Customer's partial home address
c. Hotel room number
d. Check-in date and out dates. Customer's credit card number and expiration date!
When you turn them in to the front desk your personal information is there for any employee to access by simply scanning the card in the hotel scanner.

An employee can take a hand full of cards home and using a scanning device, access the information onto a laptop computer and go shopping at your expense.

Simply put, hotels do not erase the information on these cards until an employee re-issues the card to the next hotel guest.

At that time, the new guest's information is electronically "overwritten" on the card and the previous guest's information is erased in the overwriting process.

But until the card is rewritten for the next guest, it usually is kept in a drawer at the front desk with YOUR INFORMATION ON IT!

The bottom line is:
Keep the cards, take them home with you, or destroy them.
Snopes debunks this urban myth at [Card Sharks].

They say,
In January 2006, Computerworld investigated the key card rumors by collecting and examining over 100 hotel card keys and found no personally identifiable information on any of them:
As part of a Computerworld investigation into the allegations, reporters and other staff members who traveled last fall brought back 52 hotel card keys over a six-week period. The cards came from a wide range of hotels and resorts, from Motel 6 to Hyatt Regency and Disney World. We scanned them using an ISO-standard card reader from MagTek Inc. in Carson, Calif. — the type anyone could buy online.

We then sent the cards to Terry Benson, engineering group leader at MagTek, for a more in-depth examination using specialized equipment. MagTek also gathered cards from its own staff. In all, 100 cards were tested.

Most cards were completely unreadable with an off-the-shelf card reader. Neither Benson nor Computerworld found any personally identifiable information on them. Based on these results, we think it's unlikely that hotel guests in the U.S. will find any personal information on their hotel card keys
We also purchased our own MagTek card scanner and have scanned several dozen magnetic room keys we acquired during our various hotel stays over the last few years and likewise found not a single key with any personal information stored on it.

Nevertheless, the rumor dies hard. In a followup report consumeraffairs.com claims that there have been instances of personal information stored on a hotel key card [Hotel Key Cards: Identity Theft Risk or Not? "Mythbusters" Aside, the Answer's Not Clear-Cut]. In some cases it's because thieves have stolen hotel key cards and entered stolen credit card information so the key cards can be used as fake credit cards. In other cases, it appears there were hotels that encoded personal information in the past. (These reports sound a lot like hearsay.)









Thursday, March 22, 2007

Forgetfulness - Billy Collins Animated Poetry

 
I was just sent this a few minutes ago. (My wife again! Is there a message here?) I'm posting this right away, partially in hono(u)r of PZ Myers who just turned 50, but mostly so I won't forget.

How RNA Polymerase Works: The Topology of the Reaction and the Structure of the Enzyme

 
Transcription is one of the most important steps in gene expression. During the elongation phase, the transcription complex moves along double-stranded DNA creating a transcription bubble by local unwinding of the helix (Transcription). As RNA is synthesized it forms a transient DNA:RNA helix at the active site of the enzyme (How RNA Polymerase Works: The Chemical Reaction). We now know what this transcription bubble really looks like, thanks to the work of 2006 Nobel Laureate Roger Kornberg

The figure on the left is taken from a review in Science magazine written by Aaron Klug (A Marvellous Machine for Making Messages). It shows the structure of the RNA polymerase II complex (Eukaryotic RNA polymerases) associated with a DNA:RNA hybrid that Kornberg's lab synthesized. They solved the structure of the co-crystal.

The solid blue and green lines represent fragments of DNA. As you can see from the diagram it is in the form of a double helix at the front end of RNA polymerase where it enters the groove on the leading edge. (The transcription complex is moving from left to right.) The DNA is gripped by the "jaw" region near the opening of the grove.

As the double-stranded region reaches the active site (identified by the purple Mg2+ ion), it unwinds to a single-stranded form creating a bubble. The bubble isn't actually seen in the crystal structure but its location can be inferred (dotted green and blue lines).

It looks like the unwinding is promoted when the DNA runs into the "wall" and is forced to make a sharp upward turn before exiting near the "clamp" where the two strands of DNA come back together to form a helix.

The blue strand of the transcription bubble is the template strand and part of it is associated with a short strand of RNA (red) behind the active site. There's a large funnel at the bottom of the enzyme that serves as a pathway from the outside to the site of polymerization. This is where nucleoside triphosphates (NTPs) enter and leave the active site. It also appears to be the site where the 3′ end of the RNA is extruded when the enzyme backs up for proofreading (backtracking).

The "bridge" part of the enzyme is required for the translocation step. This is the step following addition of a ribonucleotide when the enzyme has to shift by one nucleotide (base pair) to the right. The new 3′ end of RNA has to be re-positioned at the active site during this shift. At the same time, one base pair of DNA is unwound by the "fork" region of the enzyme and one base pair is reformed at the back end of the bubble by the "zipper" region.

The "bridge" acts like a flexible ratchet allowing a shift of one base pair while maintaining a grip on the growing end of the RNA molecule. This movement is steered by the "rudder."

Most of these terms ("bridge," "rudder" etc.) refer to short α helices or loops within RNA polymerase and almost all of them are part of the conserved β and β′ subunits. The same features are seen in the bacterial enzymes although the resolution of the bacterial enzyme structures is not good enough to decipher the translocation step. This is one of the achievements of the Kornberg group in the two famous papers (Gnatt et all, 2001; Cramer et al., 2001).
Gnatt, A.L., Cramer, P. , Fu, J., Bushnell, D.A., and Kornberg, R.D. (2001) Structural Basis of Transcription: An RNA Polymerase II Elongation Complex at 3.3 Å Resolution. Science 292:1876 - 1882.

Cramer, P. , Bushnell, S.A. and Kornberg, D.A. (2001) Structural Basis of Transcription: RNA Polymerase II at 2.8 Ångstrom Resolution. Science 292:1863 - 1876.