Dara Ó Briain tells us who he would put in a big sack and what he would do with them ...
[Hat Tip: Pharyngula]
Wednesday, July 22, 2009
Who goes in the sack?
Dara Ó Briain tells us who he would put in a big sack and what he would do with them ...
Lunch with a winner
Cody Cobb was the winner of Monday's Molecule #129. He lives in New Jersey where he is about to start graduate school at Rutgers. If you live in New Jersey you look forward to traveling, so Cody decided to fly up to Toronto for the day to collect his lunch. Because this was his first time in Canada, I decided to splurge and take him to a restaurant with white table cloths.
Cody has been blogging for many years—much longer than me. We had a good time talking about blogs and their
Of course no first time visit to Canada would be complete without ...
The New Seven Wonders of Nature
There are 28 finalists in the running for the New 7 Wonders of Nature. You can see the list here.Guess who didn't make the cut? Niagara Falls wasn't even on the list of possible wonders because the Americans in New York State didn't want to spend money to promote the Falls as a legitmate contender. (I assume the Canadians didn't want to foot the entire bill themselves.)
If you're Canadian you can vote for the Bay of Fundy and if you're American you can vote for the Grand Canyon. Australians, Germans, Irish, South Africans and Italians can all vote for a 7th wonder form their own country. Even the Swiss have an entry.
If you're from the United Kingdom, you are out of luck. Apparently there's nothing wonderful in the UK.
[Photo Credit: The Eire Hiker]
Tuesday, July 21, 2009
Direction and Purpose in Evolution
If you put two people together who believe that natural selection is the only important mechanism of evolution and that humans are the only, and best, end product of evolution, then this is what you get.
Watch Robert Wright and Daniel Dennet discuss direction and purpose in evolution.
Now imagine what the discussion would look like if they really understood the important role of chance and accident in evolution and, instead of humans, they used lobsters, ginkgo trees, shiitake mushrooms, rotifers, and cyanobacteria as examples of modern evolved species with three billion years worth of ancestors.
Even worse, think about the octopus. Is there any sane person who would point to the existence of those eight-legged slimeballs as evidence that evolution must have a direction and a purpose?
[Hat Tip: Robert Wright]
Monday's Molecule #130: Winner?
The "molecule" is Rous Sarcoma Virus or RSV. It's a retrovirus, specifically an alpharetrovirus. Other types of retrovirus include Lentivirus (e.g. HIV).
Unless you're an expert, you really can't tell from the diagram whether this is an alpharetrovirus or some other type of retrovirus. That's why I provided some clues linking this virus to last week's molecule and Nobel Laureates.
The Nobel Laureate is Peyton Rous.
Bill Chaney was the only person who got the right answer and he isn't eligible. There is no winner this week. Most of you guessed that it was HIV. One person—who shall not be named—guessed RSV and HIV with a total of five possible Nobel Laureates. That's only worth part marks. I'm expecting this person to be a winner real soon!
I thought last week's molecule would be a challenge but Sandwalk readers came up with the correct answer even in the middle of summer in the Northern hemisphere. Considering how well you did last week, following up with this week's "molecule" should be a gift.Identify the thing shown here and relate it to a Nobel Laureate.
The first person to identify the "molecule" and the Nobel Laureate(s), wins a free lunch. Previous winners are ineligible for six weeks from the time they first won the prize.
There are six ineligible candidates for this week's reward: Bill Chaney of the University of Nebraska, Ian Clarke of New England Biolabs Canada in Pickering ON, Canada. Dima Klenchin of the University of Wisconsin at Madison, Dara Gilbert of the University of Waterloo, Anne Johnson of Ryerson University, and Cody Cobb, soon to be a graduate student at Rutgers University in New Jersey.
I have an extra free lunch for a deserving undergraduate so I'm going to continue to award an additional prize to the first undergraduate student who can accept it. Please indicate in your email message whether you are an undergraduate and whether you can make it for lunch.
THEME:
Nobel Laureates
Send your guess to Sandwalk (sandwalk (at) bioinfo.med.utoronto.ca) and I'll pick the first email message that correctly identifies the molecule(s) and names the Nobel Laureate(s). Note that I'm not going to repeat Nobel Prizes so you might want to check the list of previous Sandwalk postings by clicking on the link in the theme box.
Correct responses will be posted tomorrow.
The image is from Butan et al. (2008) [doi: 10.1016/j.jmb.2007.12.003]
What Is Accommodationism?
Are you uninterested in the debate about accommodationism but secretly want to know what it's all about? Here's a brief summary that will get you up to speed without having to wade through all the rhetoric [What is accommodationism?].
It comes with cartoons.
[Hat Tip: John Wilkins]
Questioning the Tree of Life
I'm going to Halifax NS (Canada) next week to attend a very exciting conference with a catchy title: Questioning the Tree of life. This is legitimate scientific debate about the tree of life metaphor and its validity in light of massive horizontal gene transfers (HGT, also known as lateral gene transfers - LGT) during the early evolution of single cell organisms. It brings together scientists and philosophers who share an interest in this problem. Should be a blast!I'm supposed to report the meeting on my blog but I don't know where I'll find the time. Here are the main speakers.
W. Ford Doolittle
Tree of Life, Tree of Cells, LUCA and other questionable entities
Jan Sapp
Thinking laterally on the tree of life: An historical overview
Olivier Rieppel
The series, the network, and the tree: Changing metaphors of order in nature
Gordon McOuat
The origins and politics of trees and non-hierarchical taxonomic systems
Rob Beiko
The impact of different LGT scenarios on simulated genome evolution
Laura Franklin-Hall
Scientific models and the history of life: Deep disagreement or mere misunderstanding?
Peter Gogarten
The indistinguishability of patterns created through gene transfer between preferred partners and patterns created through shared ancestry
Joel Velasco
Inferring phylogenetic networks
Sina Adl
Specimen choice and the implications of modern technology in tree construction
Jeffrey Lawrence
Fragmented speciation in bacteria: The failure of a coalescent model
Greg Morgan
Defining biodiversity in a world with horizontal gene transfer
Yan Boucher
Evolutionary units: Breaking down species concepts
Dick Burian
Conceptual revisions deriving from the loss of the Tree
Maureen O’Malley
Philosophy of biology, Ernst Mayr, and the Tree of Life
Eric Bapteste
Lateral thinking about trees
Lisa Gannett
Trees, trellises, and the Garden of Eden
Andrew Hamilton
TOL issues in macrobes as they relate to taxonomic practice
James Mallet
Was Darwin wrong about the nature of species and speciation?
James McInerney
LUCA and LECA: Gene genesis in the genome of Eden
Chris. Malaterre
On the roots of the tree of life
Bill Martin
Endosymbiosis and gene transfers from endosymbionts, the most glaring insult to the tree
John Archibald
Genic and genomic threads in the tapestry of photosynthetic life: Implications for ‘tree thinking’
Fréd. Bouchard
Endosymbiosis in light of reflections on symbiosis and the superorganism
Rob Wilson
On arguments over the tree of life
Andrew Roger
Deconstructing deconstructions of the Tree of Life: Why a tree of microbes might be realizable, meaningful and useful
John Dupré
Analysing analyses of Tree of Life arguments: A commentary on Wilson and Roger
Susan Spath
Cultural politics and the Tree of Life
Monday, July 20, 2009
Nobel Laureates: J. Michael Bishop and Harold Varmus
The Nobel Prize in Physiology or Medicine 1989
"for their discovery of the cellular origin of retroviral oncogenes"
J. Michael Bishop (1936 - ) and Harold E. Varmus (1939 - ) won the Noble Prize in 1989 for proving that viruses contain a cancer-causing gene derived from the genome of the organism they infect. Specifically, they showed that chicken Rous Sarcoma Virus (RSV) carried an oncogene called v-src and this gene was an intronless version of a normal chicken gene called c-src.The discovery had tremendous implications in many fields. Not only did it explain the origins of a particular chicken cancer but it also suggested that there where many other oncogenes in other well-known retroviruses. This turned out to be correct and several dozen such oncogenes have been discovered (e.g. abl, fos, jun, and erb among others).
The discovery also ignited a burst of activity in signaling because the c-src gene encodes a tyrosine kinase. This is an enzyme that adds phosphate groups to proteins thereby affecting their activity. Such enzymes belong to pathways triggered by specific signals leading to the regulation of growth and cell division.
The discovery lent support to the idea that small changes in regulatory pathways could have large effects—in this case converting a normal cell to a cancer cell. This idea fit nicely with the work of developmental biologists who were showing that single genes could regulate entire developmental pathways. It meant that large-scale changes in morphology during evolution could be effected by small changes (mutations) in the genome.
Finally, the work of Bishop and Varmus helped change our view of the genome. Not only do retrovirus sequences pop in and out of the genome but they can also capture cellular genes by converting them to retrogenes. The work confirmed the idea that genomes were dynamic—a idea that began with transposons. Not only that, the discovery of the retrogene, v-src, showed us that introns were almost certainly not an essential component of a gene.
In my opinion, this is one of the most significant scientific advances of the 2oth century. There aren't many achievements that really count as breakthroughs because either the work was done in many labs and came out piecemeal, or the result wasn't very significant. This is one achievement that truly was a big step forward in biology.
By 1989, the press releases from the Karolinska Institute were becoming excellent educational tools for the scientifically literate general public. In this case, the press release explains how oncogenes cause cancer. I'm going to include the entire Press Release (below) because it's so good.
THEME:
Nobel Laureates
Summary
The discovery awarded with this year's Nobel Prize in Physiology or Medicine concerns the identification of a large family of genes which control the normal growth and division of cells. Disturbances in one or some of these so-called oncogenes (Gk ónco(s) bulk, mass) can lead to transformation of a normal cell into a tumor cell and result in cancer.
Michael Bishop and Harold Varmus used an oncogenic retrovirus to identify the growth-controlling oncogenes in normal cells. In 1976 they published the remarkable conclusion that the oncogene in the virus did not represent a true viral gene but instead was a normal cellular gene, which the virus had acquired during replication in the host cell and thereafter carried along.
Bishop's and Varmus' discovery of the cellular origin of retroviral oncogenes has had an extensive influence on the development of our knowledge about mechanisms for tumor development. Until now more than 40 different oncogenes have been demonstrated. The discovery has also widened our insight into the complicated signal systems which govern the normal growth of cells.
Cellular Oncogenes Discovered by the Use of Retrovirus
The term oncogene was introduced in the middle of the 1960s to denote special parts of the genetic material of certain viruses. It was believed that this part of the genetic material could direct the transformation of a normal cell into a tumor cell under the influence of other parts of the viral genetic material, alternatively via chemical or physical effects. The favourite theory of the time was that virus-mediated cell-to-cell transmittance of oncogenes was the origin of all forms of cancer. This view was later proven to be incorrect.
The original discovery of an oncogenic virus was made in 1916 by Peyton Rous working at the Rockefeller Institute in New York. Fifty years later Rous received the Nobel Prize in Physiology or Medicine. Rous virus, as the infectious agent later was named, is a member of a large virus family named retroviruses. The genetic material of these viruses is RNA (ribonucleic acid). This RNA can be transcribed into DNA (deoxyribonucleic acid) by a unique enzyme in the virus, reverse transcriptase. The 1975 Nobel Prize in Physiology or Medicine was awarded to David Baltimore, Renato Dulbecco and Howard Temin partly for the discovery of this enzyme.
Reverse transcription of the genetic material of the virus into DNA has the important consequence that it can become integrated into the chromosomal DNA in the cells. It was through investigations of Rous virus that this year's laureates Michael Bishop and Harold Varmus in 1975 could demonstrate the true origin of oncogenes. They used one variant of Rous virus which contained an oncogenic gene (Figure 1) and another variant which lacked this gene. By use of these viruses they managed to construct a nucleic acid probe which selectively identified the oncogene. This probe was used to search for the corresponding genetic material in DNA from different cells. It was then found that oncogene-like material could be detected in different species throughout the animal kingdom, in fact even in simple organisms comprising only a few cells. Furthermore, it was shown that the gene had a fixed position in the chromosomes of a certain species, and that the gene, when it constituted part of the cellular genetic material, was divided into fragments (a mosaic gene) (Figure 1).Figure 1. The difference between an oncogene in a virus and in a cell. In retroviruses causing tumors there is a separate segment of transforming nucleic acid which has been derived from a cell. The cellular gene is split (a mosaic gene) whereas the oncogene in the virus is continuous.These findings led to the remarkable conclusion that the oncogene in the virus did not represent a true viral gene but a cellular gene which the virus had picked up far back during its replication in cells and carried along. This cellular gene was found to have a central function in the cells. It controlled their growth and division.
Through these studies of the abnormal, i.e. the diseased state, it was possible to elucidate critical normal cellular functions - a not uncommon situation in biomedical research. The original discovery of a cellular oncogene led to an intensive search for further similar genes. The explosive development of this field of research has led to the identification of more than 40 different oncogenes which direct different events in the complex signal systems that regulate the growth and division of cells. Changes in any one or more of these oncogenes may lead to cancer.
Balanced Cellular Interactions - A Biological Wonder
Symmetrical and asymmetrical, multicellular structures develop from the fertilized ovum by a process of differentiation about which only limited knowledge is available. In the fully developed individual carefully balanced conditions prevail. Damage of an organ elicits sophisticated repair processes which lead to restitution of the original condition of the organ. However, if a single cell escapes the network of growth control the result may be an abnormal local proliferation of cells or in the worst case a cancer implying the dissemination of cells running amok.
The development of a cancer is a complicated process involving several consecutive changes of the genetic material. Studies of cellular genes (proto-oncogenes) corresponding to the viral oncogenes, has started to shed light on the intricate systems which control normal cellular growth and division.
Cellular Oncogene Products Constitute Links in Signal Chains which Regulate Growth and Division of Cells
The regulation of growth and division of cells has turned out to be much more complicated than originally believed. Cellular oncogene products with different properties act in different positions of elaborate signal systems (Figure 2). In order to transmit signals from one cell to the other or from one cell to itself there are growth factors. These factors appear in the fluids surrounding cells. There are examples of oncogene products, viz. proteins produced in the cytoplasm, which can act as growth factors. Thus, it was found that the product of the sis1) gene was closely related to a previously identified growth factor PDGF (Platelet Derived Growth Factor).Figure 2. Oncogene products are links in signal chains that stretch from the cell surface to the genetic material in the cell nucleus. This chain is composed of (1) growth factors, (2) growth factor receptors, (3) signal transducing proteins in cell membranes, (4) phosphokinases in the cytoplasm and (5) proteins transported from the cytoplasm into the nucleus where they bind to DNA. The localization of different oncogene products (Sis, ErbB, Ras, Src, Myc) is schematically indicated.In order for a growth factor to be able to interact with a cell there has to be membrane structures, receptors, to which they can bind. There are several oncogene products which represent receptors in the cytoplasmic membrane of the cells, e.g. ErbA, Fms, Kit. These receptors have a unique enzymatic activity. They are so-called kinases with a capacity to phosphorylate (=add a phosphate group) the amino acid tyrosine. There are two more groups of oncogene products with phosphokinase activity; firstly tyrosine/phosphokinase which lack receptor function and is located at the inside of the cytoplasmic membrane, and secondly serine/threonine phosphokinase which is found in the cytoplasm.
Thus, oncogene products function as links in signal chains stretching from the surface of the cell to the genetic material in the nucleus. In the cytoplasm there is one more group of oncogene products. These are called Ras and are related to important cellular signal factors called G-proteins.
Finally, there is a large number of oncogene products which are located in the nucleus of the cell, i.e. Myc, Myb, Fos, ErbA and others. These products direct the transcription of DNA into RNA and therefore play a critical role in the selection of proteins to be synthesized by the cell.
Cancer - A Complex, Biological Sequence of Events
Changes in the genetic material constitute the basis for the development of all cancer. Generally there are several consecutive such changes which influence different steps in the signal chains described above. Therefore, one should à priori not expect to find one single clue to the mechanism of origin of cancer. However, application of the expanding knowledge in the oncogene field allows us to start comprehending the disharmonic orchestration behind abnormal cellular growth.
It is conceptually incorrect to speak about "cancer genes". However, historical circumstances explain why the oncogene terminology was introduced before a designation of the corresponding normal cellular genes was proposed. From the point of view of cancer the important matter is to compare oncogenes in normal cells and in tumor cells.
Oncogenes as a Cause of Cancer
The majority of oncogenes have been discovered in experimental studies using retroviruses. However, in a few cases oncogenes were identified by the use of an alternative technique, i.e. genetic material was isolated from tumor cells of non-viral origin and transferred (transfected) to other cells prapagated in culture. The cells receiving the DNA changed growth pattern, and further characterization of the transfected genetic material revealed the presence of oncogenes.
Two principally different forms of activation of oncogenes can be distinguished. Firstly, the normal cellular oncogene is hyperactive, and secondly the oncogene product is altered so that it can no longer be regulated in a normal way. There are several examples of these types of activation of oncogenes.
The discovery of oncogenes was as mentioned originally made by the use of retroviruses. This infers that genetic control elements in the virus itself can be responsible for the abnormal expression of the oncogene. However, in many cases it was found that alterations of the transferred oncogene contributed to its accentuated expression.
There are retroviruses which lack oncogenes but still can induce cancer. This is due to the fact that the virus has inserted its genetic material (in the form of DNA) very close to a normally occurring oncogene in the genetic material of the cell. This may result in an increased turn-over of the oncogene which may lead to abnormal cellular growth. The corresponding phenomenon can also occur in the absence of retroviruses. In this case there is a reorganization of the genetic material in the cell. Such a reorganization may occur within a single chromosome or by exchange of material between chromosomes. Repeated copying of a normal oncogene can lead to its amplification in the chromosome and consequently to increased amounts of the oncogene product. In certain brain tumors, glioblastomas, an amplified erbB-gene has been found, and a correspondingly increased neu-gene activity was shown in some forms of breast cancer.
The same effect can be seen when there is a reciprocal exchange of segments between chromosomes (translocation). Thus the normal myc-gene on chromosome 8 has been translocated to chromosome 14 in many patients with Burkitt's lymphomas (Figure 3). The insertion of the myc-gene containing chromosome segment is such that it becomes located close to hyperactive genes directing the synthesis of antibody protein. As a consequence the myc-gene becomes activated. Chromosome translocations occur in many different tumors. Chromosome analysis can therefore be of considerable value for localization of genetic changes in the genome critical for tumor development.Figure 3. Chromosome translocation in Burkitt's lymphoma. Segments have been exchanged between chromosomes 8 and 14 which has activated the oncogene myc.Oncogenes with point mutations have been observed in many tumors. These mutations may cause alterations in the amino acid composition of the gene product. A well-known example of such a modification is the exchange of amino acid 12 from glycine to valine in the ras gene product which has been observed in human tumor material. The mutation may also be somewhat more extensive leading to the absence of part of the protein (deletion). Different examples of modified oncogenes in human tumor material are given in Table I.The Importance of Viruses for Cancer in Man
Cancer is not a contagious disease. However, infectious agents like viruses can contribute to the origin of cancer. Thus, it is by use of retroviruses that most oncogenes were identified, the starting materials in such investigations often being highly specialized, experimentally derived tumors. It seems likely that retroviruses play a relatively limited role for the development of cancer under natural conditions. The only known example in man in which a retrovirus infection contributes to the origin of cancer is the HTLV-1 associated lymphomas which occur in Japan.
However, there are other kinds of viruses which can contribute to the development of tumors in man. All these viruses have DNA as their genetic material. As examples can be mentioned papillome (wart) viruses and Epstein-Barr virus, a type of herpes virus. Certain types of papillome viruses play a role for the development of cervical cancer in the genital tract, while Epstein-Barr virus is an important factor for the development of Burkitt's lymphomas in Africa and nasopharyngeal cancer in Asia. However, in all these cases factors in addition to the virus infections are required for the cancer to develop.
References
J.M. Bishop: Oncogenes. Scientific American, 1982, 246, 68-78.
T. Hunter: The Proteins of Oncogenes. Scientific American, 1984, 251, 60-69.
C-H. Heldin & B. Westermark: Tillväxtfaktorer och onkgener. Läkartidningen 1988, 85, 497-499.
E. Norrby: I: Våra virus. Virus och cancer. Allmänna Förlaget, 1987, sid. 66-74.
1) All oncogenes are identified by the use of three letter abbreviations. In addition cellular and viral oncogenes are sometimes distinguished by c- and v- prefixes, respectively, e.g. c-src and v-src.
[Photo Credit: UCSF]
The images of the Nobel Prize medals are registered trademarks of the Nobel Foundation (© The Nobel Foundation). They are used here, with permission, for educational purposes only.
The Collapse of the "Dawkins Dogma"
Fern Elsdon-Baker has written an article for New Scientist entitled Comment: The Dawkins dogma.It begins with a description of the selfish gene and Darwinian orthodoxy as described by Richard Dawkins. All of this is about to change, according to Elsdon-Baker.
My excitement increased as I read on. Finally, New Scientist is about to wake up to the fact that random genetic drift—a non-Darwinian mechanism—plays an important role in evolution. At long last their readers are going to learn what evolutionary biologists have known for half a century.
No such luck. The challenge to the Richard Dawkins view of evolution comes from .... wait for it .... epigenetics and Lamarckian evolution!
Not only that, lateral gene transfer is toppling the tree of life at its roots.
Who is Fern Elsdon-Baker? She's identified in the by-line as, "Fern Elsdon-Baker is head of the British Council's Darwin Now project and author of The Selfish Genius, published this month."
Turns out she has recently (2006?) completed her Ph.D. in the history and philosophy of science. Her thesis topic was,
Theories of inheritance in the nineteenth and twentieth centuries : The role of historiographical constraints on contemporary scientific research, with particular emphasis on the role of "Weismann's Barrier" in Darwinian and Neo-Darwinian debatesHer book, which is apparently an attack on Richard Dawkins will be published next week. It seems to be an extension of her thesis work, judging by the early reviews.
BTW, you can read one of these reviews of The Selfish Genius on the The Times website. It looks like her focus is on epigenetics and the inheritance of acquired characteristics. There's no indication from the review that she has clued into the adaptationist vs pluralist controversy that's been at the heart of most criticism of Dawkins for the past thirty years.
This seems strange for a person who just got a Ph.D. for studying evolutionary theory.
At least New Scientist had the good sense to identify the article as "comment." This should alert readers to take Elsdon-Baker's opinion with a large grain of salt. It looks very much like the article is part of a publicity campaign associated with the upcoming release of her book.
Move along folks. There's nothing new here. Modern (pluralist) evolutionary theory is not about to be overturned.
Can Factual Information Change People's Minds?
Can factual information change people's minds? Most people assume the answer is "yes." After all, if people believe something that isn't true then exposing them to the truth should cause them to abandon their beliefs, right?
Wrong. There's plenty of evidence that life is much more complicated. An interesting posting on MotherJones.com entitled The Backfire Effect, alerts us to a study suggesting that knowledge may even have the opposite effect to what you expect. (Hat Tip: Canadian Cynic)
The paper is here.
The persistence of political misperceptions
Brendan Nyhan and Jason Reifler
The authors review the literature and conclude that substantial numbers of people are quite resistant to facts when they hold strong opinions. Surprisingly, some people actually become more convinced they are right after hearing facts that contradict their belief. This phenomenon, called "The Backlash Effect," is actually familiar to us in another context. One example given in the paper is, "... that hearing a Democrat argue against using military force in some cases causes Republicans to become more supportive of doing so."
In one of the studies conducted by Nyhan and Reifler, students were divided into two groups. Both groups read a news report quoting from a speech by President Bush in October 2004—six months after the invasion of Iraq. One group read an extended news report describing the Duelfer Report, which all but proved that Iraq did not have weapons of mass destruction before the war began. The additional information counts as "the correction."
Students were then asked whether they agreed with the following statement.
Immediately before the U.S. invasion, Iraq had an active weapons of mass destruction program, the ability to produce these weapons, and large stockpiles of WMD, but Saddam Hussein was able to hide or destroy these weapons right before U.S. forces arrived.Here's the result ...
For very liberal subjects, the correction worked as expected, making them more likely to disagree with the statement that Iraq had WMD compared with controls. The correction did not have a statistically significant effect on individuals who described themselves as liberal, somewhat left of center, or centrist. But most importantly, the effect of the correction for individuals who placed themselves to the right of center ideologically is statistically significant and positive. In other words, the correction backfired – conservatives who received a correction telling them that Iraq did not have WMD were more likely to believe that Iraq had WMD than those in the control condition.I'm pretty skeptical about these sorts of studies because there are so many variables and the sample sizes are quite small. Nevertheless, this "backfire effect" makes some sense given my own experience in trying to debate various issues.
I exhibit it myself sometimes. Faced with opponents who are vigorously disagreeing with me I can feel myself being driven to a hardened, more extreme, position than I would otherwise hold. In other words, when presented with uncomfortable facts that contradict my point of view, I sometimes work even harder to refute or rationalized those facts. That's more comforting than being forced to admit I'm wrong.
My opponents do this too. In fact, they do it far more often than I do because they are far more likely to start off being wrong.
The bottom line is that you have to be careful to remain objective in the face of factual information. Be prepared to re-evaluate your position if the facts are against you. And don't assume that your opponents will be swayed by correcting their misperceptions. That's only the first step toward changing their minds.
The paper goes on to describe other studies and it discusses possible explanations. It's a good read and I recommend it.
Monday's Molecule #130
I thought last week's molecule would be a challenge but Sandwalk readers came up with the correct answer even in the middle of summer in the Northern hemisphere. Considering how well you did last week, following up with this week's "molecule" should be a gift.Identify the thing shown here and relate it to a Nobel Laureate.
The first person to identify the "molecule" and the Nobel Laureate(s), wins a free lunch. Previous winners are ineligible for six weeks from the time they first won the prize.
There are six ineligible candidates for this week's reward: Bill Chaney of the University of Nebraska, Ian Clarke of New England Biolabs Canada in Pickering ON, Canada. Dima Klenchin of the University of Wisconsin at Madison, Dara Gilbert of the University of Waterloo, Anne Johnson of Ryerson University, and Cody Cobb, soon to be a graduate student at Rutgers University in New Jersey.
I have an extra free lunch for a deserving undergraduate so I'm going to continue to award an additional prize to the first undergraduate student who can accept it. Please indicate in your email message whether you are an undergraduate and whether you can make it for lunch.
THEME:
Nobel Laureates
Send your guess to Sandwalk (sandwalk (at) bioinfo.med.utoronto.ca) and I'll pick the first email message that correctly identifies the molecule(s) and names the Nobel Laureate(s). Note that I'm not going to repeat Nobel Prizes so you might want to check the list of previous Sandwalk postings by clicking on the link in the theme box.
Correct responses will be posted tomorrow.
The image is from Butan et al. (2008) [doi: 10.1016/j.jmb.2007.12.003]
Sunday, July 19, 2009
The Origin of Dachshunds
A draft sequence of the dog (Canis lupus familiaris) genome has been available for several years. One of the reasons for working with dog genes and genomes is the fact that there are many different breeds. Since these breeds differ genetically and morphologically, there's a distinct possibility that the genes for various characteristics can be identified by comparing variants from different breeds. One of the exciting possibilities is that some interesting behavioral genes could be identified since many breeds of dog are loyal, easy to train, and intelligent.1
In addition to possible behavioral genes, one can identify many genes affecting morphology. One of them is the gene affecting short legs in various breeds, including dachshunds. Parker et al. (2009) identified an extra gene in short-legged breeds. The extra gene is a retrogene of the normal gene encoding fibroblast growth factor 4 (fgf4).
What is a retrogene? It's a derivative of the mature mRNA of a normal gene. Recall that most mammalian genes have introns and the primary transcript contains extra sequences at the two ends, plus exons that encode the amino acid sequence of a protein, plus intron sequences that separate the exons.
This primary transcript is processed to produce the mature messenger RNA (mRNA) that is subsequently translated by the translation machinery in the cytoplasm. During processing, the intron sequences are spliced out, a 5′ cap is added to the beginning of the RNA, and a string of "A" residues is added to the terminus (= poly A tail).
On rare occasions the mature mRNA can be accidentally copied by an enzyme called reverse transcriptase that converts RNA into single-stranded DNA. (The reverse of transcription, which copies DNA into RNA.) The single-stranded DNA molecule can be duplicated by DNA polymerase to make a double-stranded copy of the original mRNA molecule.
This piece of DNA may get integrated back into the genome by recombination. This is an extremely rare event but over the course of millions of years the genome accumulates many copies of such DNA sequences. In the vast majority of cases the DNA sequence is not expressed because it has been separated from its normal promoter. (Sequences that regulate transcription are usually not present in the primary transcript.) These DNA segments are called pseudogenes because they are not functional. They accumulate mutations at random and the sequence diverges from the sequence of the normal gene from which they were derived.
Sometimes the DNA copy of the mRNA happens to insert near a functional promoter and the DNA is transcribed. In this case the gene may be expressed and additional protein is made. Note that the new retrogene doesn't have introns so the primary transcript doesn't require splicing in order to join the coding regions (exons). The fgf4 retrogene inserted into the middle of a LINE transposable elements and the LINE promoter probably drives transcription of the retrogene.
The short-legged phenotype is probably due to inappropriate expression of the retrogene in the embryo in tissues that generate the long bones of the legs. The inappropriate expression of fibroblast growth factor 4 causes early calcification of cells in the growth plates—these are the cells that regulate extension of the growing bones. The result is short bones that are often curved.
Breeders selected for this anomaly and this is part of what contributed to the origin of dachshunds and other short-legged dogs.
There's a reason why dogs are such good species for discovering the functions of many genes. It's because of the huge variety of different breeds. Is there a reason why the species has more morphological variation than other species of animals? Probably, but we don't know the reason. Here's how Parker et al. begin their paper.
The domestic dog is arguably the most morphologically diverse species of mammal and theories abound regarding the source of its extreme variation (1). Two such theories rely on the structure and instability of the canine genome, either in an excess of rapidly mutating microsatellites (2) or an abundance of overactive SINEs (3), to create increased variability from which to select for new traits. Another theory suggests that domestication has allowed for the buildup of mildly deleterious mutations that, when combined, create the variation observed in the domestic dog (4).We still have a lot to learn about evolution.
[Photo Credit: Dog Gone Good]
1. You can see why working with the cat genome wouldn't be as productive.
Parker, H.G., Vonholdt, B.M., Quignon, P., Margulies, E.H., Shao, S., Mosher, D.S., Spady, T.C., Elkahloun, A., Cargill, M., Jones, P.G., Maslen, C.L., Acland, G.M., Sutter, N.B., Kuroki, K., Bustamante, C.D., Wayne, R.K., and Ostrander, E.A. (2009) An Expressed Fgf4 Retrogene Is Associated with Breed-Defining Chondrodysplasia in Domestic Dogs. Science. 2009 Jul 16. [Epub ahead of print] [PubMed] [doi: 10.1126/science.1173275]
Pascal's Wager
Believe it or not, there are otherwise intelligent people out there who actually take Pascal's Wager seriously. Here's what happens ...
Are all Scientists on the Same Team?
I want to be like Janet D. Stemwedel when I grow up.She has an amazing ability to think clearly and it's combined with an equally amazing ability to get her clear thoughts down on paper (or monitors). She is one of the reasons why I like
Her latest example is a discussion of Unscientific America, the book by Chris Mooney and Sheril Kirshenbaum that's causing so much turmoil in the blogosphere. I strongly urge you to read her posting from late Friday night called Unscientific America: Are scientists all on the same team?.
I posted a comment on Adventures in Ethics and Science in response to her posting. What I'm trying to do is explain why it is wrong for scientific organizations to take a position that excludes a large number of scientists. I'm including my comment here so that Sandwalk readers can have their say.
Excellent post, Janet. I agree with everything you say—except maybe for a few minor quibbles.
Chris and Sheril have missed the point about scientists having multiple goals and that's why many of their criticisms are misguided.
What can we do to find common goals that all scientists can share? I'd like to make one small suggestion. Scientific organizations such as AAAS, NAS, NIH, NSF etc. should remain strictly neutral with respect to religion. They should never take a stance on whether science and religion are compatible or incompatible. They should never promote the views of theistic scientists as being examples of excellent science BECAUSE these scientists are religious.
We all know that AAAS and NAS don't behave this way. They specifically use Francis Collins and Ken Miller as examples of good scientists who are also religious. They explicitly support the philosophical position that science is compatible with evangelical Christianity (Collins) and Roman Catholicism (Miller).
If all such organizations refrained from taking sides then ALL scientists, atheist and theist alike, could get behind their goals and support them. As soon as they start promoting the philosophical position of science/religion compatibility, they lose some of their potential supporters. The supporters they lose are the atheists who believe that science is not compatible with many of the beliefs of established religions.
The strict neutrality that I advocate should extend to the leadership of these organizations. Leaders of scientific organizations should not be prominently identified as supporters of religion or opponents of religion. This applies to the Director of NIH as well as other leadership positions.
Personally, I would extend the goal of strict neutrality to organizations like the National Center for Science Education (NCSE). If they maintain a big tent then all scientists, atheists and theists alike, can support their main goals. As soon as an organization like NCSE starts to promote the compatibility of science and religion by favoring theistic evolutionists over atheists—especially atheists who are opposed to compatibility—they create divisions. I don't think it is necessary for them to abandon and antagonize the vocal atheist scientists. NCSE disagrees, they have made a political decision to choose compatibility over neutrality because it advances their primary goal, which is separation of church and state.
These are complex issues. I don't get the impression that Chris and Sheril are aware of the complexity.
Web Site Story
I have a confession to make. I've always been a fan of West Side Story. I never saw the Broadway production but I saw the movie and even bought the soundtrack album back in 1961. Some of the songs are true classics that are still being played on the radio today (Especially if you have satellite radio and listen to the 60s channel or the showtime channel.
) I bet every one of you can since a few bars of "Maria", "Tonight", "America", "I Feel Pretty", or "Somewhere" and probably most of you know a line or two from "Gee, Officer Krupke" and "Something's Coming".
Here's a very clever and funny, updated, version that was posted on A Blog Around the Clock.
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