Get a Job in Toronto

 

DEPARTMENT OF MOLECULAR GENETICS
UNIVERSITY OF TORONTO
Applications are invited for a Tenure-Stream Position in Developmental Biology

The Department of Molecular Genetics at the University of Toronto invites applications for a tenure-stream appointment in developmental biology. The appointment at the rank of Assistant or Associate Professor, will commence on or after July 1, 2010, and will be located in the Medical Sciences Building on the downtown campus of the University of Toronto.

We seek candidates whose research addresses a fundamental problem in animal developmental biology using either established (mouse, frog, fish, fly, nematode worm, sea urchin, tunicate, etc.) or up-and-coming (stickleback, cnidarian, planarian, arthropod, choanoflagellate, etc.) models. The successful candidate will complement and enhance the Department’s existing strengths in developmental biology, model organism genetics, and other areas.

The Department is one of the premier academic life sciences departments in Canada, with 90 full-time faculty members and 300 graduate students (Molecular Genetics). The candidate will benefit from the interdepartmental Collaborative Graduate Program in Developmental Biology as well as from recent efforts at the University of Toronto and affiliated teaching hospitals to expand research in stem cell biology; cell, tissue and whole-animal imaging; proteomics, genomics and bioinformatics through new infrastructure and academic programs. Candidates must have a Ph.D. degree or equivalent, postdoctoral experience, and an established record of research accomplishment. The successful candidate will be expected to mount an original, competitive, and independently funded research program, and to have a commitment to undergraduate and graduate education.

We encourage you to submit your application online (Jobs: faculty). Please ensure that you include a Curriculum vitae that includes current and long-term research objectives. If you are unable to apply online (or alternatively have large document to send), please submit your application and other materials to: Dr. Howard Lipshitz, Chair, Department of Molecular Genetics, University of Toronto, 1 King’s College Circle, Rm. 4286, Toronto, Ontario M5S 1A8 Canada. Applicants should also arrange that three letters of reference be sent directly to Dr. Lipshitz, or have them emailed to mogen.chair@utoronto.ca Applications and referee letters will be accepted until November 15, 2009 or until the position is filled.

The University of Toronto offers the opportunity to teach conduct research and live in one of the most diverse cities in the world. The University is strongly committed to diversity within its community and especially welcomes applications from visible minority group members, women, Aboriginal persons, persons with disabilities, members of sexual minority groups, and others who may contribute to further diversification of ideas.

All qualified candidates are encouraged to apply; however, Canadians and permanent residents of Canada will be given priority.

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The Last Universal Common Ancestor

 
Jeffrey Wong is a former member of our Department¹ and the author of the best theory on the origin of the genetic code [see: Amino Acids and the Racemization "Problem"]

LUCA, LECA and LBACA--Root of Life and Roots of the Biological Domains

Dr. Jeffrey Wong
Department of Biochemistry
Hong Kong University of Science and Technology

4:30 pm, September 10
Medical Sciences Building room 4171

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His mother's photograph is on the wall of graduates on the first floor of our building. She graduated from medical school in 1929.

The Most Expensive Health Care System in the World

 
The USA has the most expensive health care system in the world. They're number 1 by a long shot.

But does the USA have the "best" health care system in the world? Is it going to change?

Change doesn't look promising. Apparently it's a lot easier to make up campaign slogans about change than it is to actually deliver.

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[Hat Tip: Genomicron]

Monday's Molecule #135: Winner!

 
Yesterday's molecule was the type II reaction center from the photosynthetic purple bacterium Rhodobacter spaeroides.

When light shines on the special pair of chlorophyll molecules known as P870, a single electron is boosted to a high energy level by absorbing a photon. This electron is transferred to an adjacent bacteriochlorophyll a heme group in a typical oxidation reaction. The single electron then travels down the electron transport pathway to a bacteriopheophytin heme and then to a quinone molecule that's part of the pathway.

In the final step, the electron reduces another quinone bound to the "mobile" site. This reduction is mediated by an iron atom (red ball). Quinol (QH₂) is released after two electrons have been transferred sequentially. The quinol molecule carrying two electrons then diffuses to a cytochrome bc complex that pumps protons across the membrane. The creation of a proton gradient drives the synthesis of ATP.

The electron deficient P870 chlorophylls are re-supplied with electrons from cytochrome c, which gets them from the chytorchrome bc complex in a cyclic reaction [see A Simple Version of Photosynthesis].

Purple bacteria are strict anaerobes—oxygen is poisonous to them so their The purple bacteria version of photosynthesis does not involve the splitting of water and generation of O₂. This is an important point since many students think that water (H₂O) is the only possible electron donor in photosynthesis. In fact, the ability to oxidize water evolved much later.

It's much better to think of photosynthesis as a light-activated oxidation-reduction system where there are several possible electron donors and acceptors.

The type II reaction center molecules are embedded in a membrane-spanning protein complex whose structure has been solved [see Nobel Laureates: Deisenhofer, Huber, and Michel]. In the version shown here, the electron donor is cytochrome c, which binds to the top part of the molecule on the exterior surface of the membrane.

Photosynthesis is a complex example of an electron transfer reaction. Rudolph A. Marcus was awarded a Nobel Prize for his work on understanding this type of chemical reaction.

This week's winner is Philip Johnson of the University of Toronto. He blogs at Biocurious. While Philip was the first to get the right answer, an honorable mention has to go to Wibowo Arindrarto from Jakata, Indonesia for the best answer.

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Your task for today is to identify the molecules with the question marks and explain (briefly) what's going on.

There's a Nobel Prize associated with the type of reaction that you're seeing here. Focus on the red arrows. The prize wasn't for this particular reaction although it is depicted in the Nobel Lecture as an example of the type of reaction that was being described. Name the Nobel Laureate.

The first person to describe the reaction and name the Nobel Laureate wins a free lunch. Previous winners are ineligible for six weeks from the time they first won the prize.

There are only three ineligible candidates for this week's reward: Alex Ling of the University of Toronto, and Markus-Frederik Bohn of the Lehrstuhl für Biotechnik in Erlangen, Germany, and Maria Altshuler of the University of Toronto

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.

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

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Monday's Molecle #135

 
Your task for today is to identify the molecules with the question marks and explain (briefly) what's going on.

There's a Nobel Prize associated with the type of reaction that you're seeing here. Focus on the red arrows. The prize wasn't for this particular reaction although it is depicted in the Nobel Lecture as an example of the type of reaction that was being described. Name the Nobel Laureate.

The first person to describe the reaction and name the Nobel Laureate wins a free lunch. Previous winners are ineligible for six weeks from the time they first won the prize.

There are only three ineligible candidates for this week's reward: Alex Ling of the University of Toronto, and Markus-Frederik Bohn of the Lehrstuhl für Biotechnik in Erlangen, Germany, and Maria Altshuler of the University of Toronto

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.

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

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Kiefer Sutherland Comments on Universal Health Care

 
You may be asking yourself why you should pay attention to an actor when it comes to health care. Watch and learn why.

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[Hat Tip: Jennifer Smith who found the original video, made for a Tommy Douglas tribute at the 2006 NDP Convention. Does this mean that Jack Bauer is a commie?

Thank God for Etsy Wednesday

 
Ms. Sandwalk's birthday is coming up and I have no idea what to get her.¹ Along comes Eva and Etsy Wednesday with a great idea [Etsy Wednesday - Periodic Table Necklaces].


I'm thinking that one of these necklaces would be even better than diamonds or gold, right?

She'll be so happy.

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1. On the other hand, after 40-odd years I've accumulated a long list of things NOT to get her.

The advantages of being close to Canada

 
Razib Khan of Gene Expression has a list [States which do well educationally, blame Canada!].

Living in a state that's close to Canada confers a number of advantages on American citizens. They are smarter, wealthier, healthier, and more likely to have voted Democrat.

Oh yeah, one other thing, being close to Canada helps prevent murder.

Alaska is an exception.

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Education vs Job Training

There's always been a healthy debate about the role of an undergraduate education. Some view it as primarily a way of preparing for a job after graduation. At most universities we have undergraduate programs that do just that—engineering, and management studies are prime examples.

Some of us think this is misguided. We think that the primary goal of a university education should be to teach students how to think. This is especially true in the arts and science programs; like a biology major, for example.

According to one view, a proper education in biology would focus on basic concepts with a view to teaching students how life works and how it evolved. Along the way, they would be exposed to critical thinking and scientific conflicts in order to learn how to think like a scientist. This approach emphasizes learning and thinking in the context of biology but it doesn't exclude lab exercises and other practical applications of biology. Those are secondary goals, not primary ones.

A good biology education should prepare students for graduate school, if that's what they want to do, but it should also produce scientifically literate citizens who may choose many other careers.

The other view would focus more attention on preparing students for a job in biology. In this case, a lot of the courses would emphasize practical aspects of biology such as how to prepare buffers and how to use computers. Graduates of such a program should be well-equipped to take a job as a lab technician as soon as they graduate.

Some of these issues were discussed at a recent conference sponsored by the American Association for the Advancement of Science (AAAS) (see, Conference Mobilizes Educators to Transform Undergraduate Biology Education).

The CEO of AAAS, Alan I. Leshner, made the following statement.

Leshner said the goal of undergraduate education should be to give students a "fundamental knowledge of what science is, and what it is not, along with some key concepts." He also cautioned the conference participants not to fall into the trap of shifting the goal toward developing a scientific workforce, but, rather, remaining concerned with science for all undergraduates.

I agree with Leshner. We should not fall into the trap of turning a university education into a job training program.

Sandra Porter of Discovering Biology in a Digital World attended the conference. She takes issue with the statement by Leshner as quoted on the website. Read her blog at: How NOT to encourage diversity in the scientific community.

Sandra is especially upset with the idea that, "participants not to fall into the trap of shifting the goal toward developing a scientific workforce, but, rather, remaining concerned with science for all undergraduates." Here's how she puts in on her blog.

I know it's unfair to jump on one sentence, but after that point, all I could think about, is that the man must be completely clueless and out of touch with the reality of both the needs of students and the life science industry. Statements that imply that workforce doesn't matter and that biology educators should avoid "falling into the trap" also imply that biology is only for those wealthy students that won't need to find jobs after college.

I have heard this from other college faculty before. Apparently you shouldn't consider a college education, and certainly, not an education in life science to be some kind of ticket to employment. SCIENCE (all of you fall down on your hands and knees, okay?) is only for those with independent means or those who plan to go to medical school.

I mean, it must be nice to just go to school and not be concerned about learning any sort of marketable skill. Unfortunately, while Leshner compliments college biology teachers for ignoring notions about job preparation, students are the ones who will pay the price. Even those who go on to graduate school, eventually have to learn bench skills.

This seems way over the top to me. Of course a good biology education will expose students to lab skills and practical aspects of biology. That's not being questioned.

It's a question of emphasis. The primary goal is to graduate scientifically literate students who understand critical thinking. At the very least, if they graduate from a biology program they should understand evolution and why nothing in biology makes sense except in its light. If they can prepare buffers and do a BLAST search then that's a bonus.

It's Sandra, not Leshner, who's promoting the idea of two kinds of student—those who can learn how to think and those who are only interested in going to university to get a job. Perhaps she's thinking mostly of education at a community college while Leshner and I are thinking about education at university?

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Monday's Molecule #134: Winner

 
The technique is partition chromatography. The example shown below could be either thin layer chromatography or paper chromatography. The principle is the same. It is nicely explained by Bill Chaney of the University of Nebraska Medical Center. Unfortunately for him, there were others who responded faster, although not as eloquently.

The technique you are referring to is partition chromatography. The sample is spotted at one end of the immobile phase and a liquid mobile phase is allowed to adsorb along the phase, often in an enclosed container, which is an necessity if the mobile phase is a mixture of volatile liquid. Because different molecules have varying affinities for the solid and mobile phases (their partition coefficient) they are carried along the direction of the flow of the mobile phase at different rates giving their Rf value. The immobile phase can be paper, thin layers of different compounds like silica gel, or ion exchange resins. It is also used in Gas Liquid and Gas Solid chromatography as well where the mobile phase is a gas.

The Nobel Laureates are Martin and Synge for inventing partition chromatography. The winner is Maria Altshuler of the University of Toronto. Congratulations Maria, you beat out a dozen others who had the right answer!

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Today's "molecule" isn't a molecule. I'm looking for the technique that's illustrated by the example shown here. Describe the technique and identify the Nobel Laureates who discovered it.

The first person to identify the technique and the Nobel Laureates, wins a free lunch. Previous winners are ineligible for six weeks from the time they first won the prize.

There are only two ineligible candidates for this week's reward: Alex Ling of the University of Toronto, and Markus-Frederik Bohn of the Lehrstuhl für Biotechnik in Erlangen, Germany.

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.

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

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The image is taken from this website on paper chromatography.

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Did Life Arise 3.5 Billion Years Ago?

J. William Schopf is a paleontologist at the University of California, Los Angeles (USA). He became famous in the 1990s for his studies of the Apec chert—ancient rocks in the northern part of Western Australia near the town of Marble Bar. Parts of these rocks have been reliably dated to 3.465 billion years ago.

Schopf claimed to have discovered bacteria fossils in these rocks. He published his results in a highly cited Science paper back in 1993 (Schopf, 1993). The title of the paper "Microfossils of the Early Archean Apex chert: new evidence of the antiquity of life" establishes his claim.

It's worth quoting the abstract of the paper because it shows the confidence Schopf exuded. Not only did he claim that the 3.5 billion year old Apex chert contained bacterial fossils but, even more astonishingly, he identified eleven different species and clearly stated that they resembled cyanobacteria.

Eleven taxa (including eight heretofore undescribed species) of cellularly preserved filamentous microbes, among the oldest fossils known, have been discovered in a bedded chert unit of the Early Archean Apex Basalt of northwestern Western Australia. This prokaryotic assemblage establishes that trichomic cyanobacterium-like microorganisms were extant and morphologically diverse at least as early as approximately 3465 million years ago and suggests that oxygen-producing photoautotrophy may have already evolved by this early stage in biotic history.

The data were immediately challenged. There were two problems, First, many paleonotologists questioned whether the "fossils" were really fossils. They suggested that the structures could easily be inorganic in nature and not remnants of living organisms. Secondly, the presence of cyanobacteria—among the most complex bacteria—is inconsistent with molecular data. Even though the early tree of life is complicated, the available evidence indicates that cyanobacteria arose late in the evolution of bacterial taxa. It's very unlikely that the earliest forms of life could be cyanobacteria, or even photosynthetic bacteria.

The publicity associated with the presumed discovery of the earliest forms of life was too much to resist. In spite of the criticisms, the "fact" of these "fossils" made it into the textbooks within months of the discovery. The original figures have often been purged from more recent editions but the widespread claim that life originated 3.5 billion years ago persists.

Schopf defended and promoted his work in a trade book—The Cradle of Life— published in 1999. In that book he appeared to address most of his critics. He insisted that his "fossils" met all the rigorous tests of science.

The Fossils Aren't Fossils

Over the years, the challengers became more and more emboldened. In 2002 Martin Brasier published a re-analysis of Schopf's original fossils and noticed that the published images were not as complete as they could be. In the figure shown here, Brasier et al. (2002) compare Schopf's original images ("b" and "c") with a larger view of the same material.

The "fossils" look much more like inorganic inclusions that just happen to resemble strings of bacteria, according to Brasier. A debate between Martin Brasier and Bill Schopf took place in April 2002 and it was widely perceived to have resulted in victory for Brasier. The "fossils" aren't fossils.

A report in Nature presented the bottom line (Dalton, 2002).

The textbooks say that oxygen-producing microorganisms evolved some 3.5 billion years ago. But as that claim and its author come under attack, the history of life on Earth may have to be rewritten...

Supporters and critics of Schopf alike describe him as a driven and tenacious character — nicknamed 'Bull' Schopf by some — whose energy and enthusiasm has done much to raise the profile of micropalaeontology, and to draw funding into the field. "He has a driving ambition to be in the limelight, and he doesn't like to admit he's wrong," says one former colleague. But these traits have led Schopf into conflict with his collaborators on at least one previous occasion.

A similar piece in Science helps drive the point home (Kerr, 2002).

The search for fossils in rocks formed before the Cambrian explosion of life 540 million years ago "has been plagued by misinterpretation and questionable results," leading paleontologist William Schopf of the University of California, Los Angeles (UCLA), once noted. Now Schopf's own claim for the oldest known fossils--fossils that have entered textbooks as the oldest ever found--is under attack as a misinterpretation of intriguingly shaped but purely lifeless minerals.

A paper in this week's issue of Nature argues that the microscopic squiggles in a 3.5-billion-year-old Australian chert are not fossilized bacteria, as Schopf claimed in a 1993 Science paper (30 April 1993, p. 640), but the curiously formed dregs of ancient hot-spring chemistry. "There's a continuum [of putative microfossils] from the almost plausible to the completely ridiculous," says lead author Martin Brasier, a micropaleontologist at the University of Oxford, U.K. "Our explanation is that they are all abiogenic artifacts."

If true, the analysis calls into question the fossil record of life's first billion years. It would also raise doubts about the judgment of Schopf, the man chosen by NASA to set the standard for distinguishing signs of life from nonlife at the press conference unveiling martian meteorite ALH84001 (Science, 16 August 1996, p. 864). But Schopf says that such speculation is unwarranted. "I would beg to differ" with Brasier's interpretation, he says. "They're certainly good fossils."

The latest paper by Pinti et al. (2009) extends earlier observations of the Apex chert that re-interpret it as a hydrothermal vent. Temperatures reached 250° during formation of the vent and the alternation between molten and cooler forms of material was not conducive to life. Furthermore, deposits of iron oxides and clay minerals could be mistaken for microfossils .

Organic Traces of Early Life?

One of the early signatures of life is trace organic matter. In theory, it is possible to distinguish between organic molecules that form by chemical processes and organic molecule that are synthesized by living organisms. The key is the ratio of the two isotopes of carbon; ¹²C and ¹³C. The common isotope is ¹²C and living organisms preferentially incorporate ¹²C when they synthesize carbohydrates, lipids, and other molecules of life.

The result is that organic molecules made in cells have a smaller percentage of the heavy isotope, ¹³C. The presence of "lighter" organic molecules is evidence of life—or so the story goes.

Even this evidence of early life is being challenged. For example, a review of the evidence for life in the 3.7 billion year old rocks of western Greenland points out two potential problems (Fedo et al., 2006). First, the material has probably been misidentified—it is not what it was claimed to be. Recent evidence suggests that the rocks are igneous, not sedimentary. Secondly, the isotope ratios may not be accurate and/or they can be explained by non-biological processes. Isotope ratios are not an unambiguous indication of life.

These problems, and others, with the Akilia rocks of western Greenland have been known for many years. They were discussed in a hard-hitting Nature News and Views article by Stephen Moorbath in 2005. You may not understand the technical details (I don't) but there's no mistaking the tone when Moorbath says ...

This persuasive discovery seems an almost inevitable, yet highly problematic, consequence to the increasing scientific doubts about the original claim. We may well ask what exactly was the material originally analysed and reported? What was the apatite grain with supposed graphite inclusions that figured on the covers of learned and popular journals soon after the discovery? These questions must surely be answered and, if necessary, lessons learned for the more effective checking and duplication of spectacular scientific claims from the outset.

To my regret, the ancient Greenland rocks have not yet produced any compelling evidence for the existence of life by 3.8 billion years ago. The reader is reminded that another debate on early life is currently in progress on 3.5-billion-year-old rocks in Western Australia, where chains of cell-like structures, long identified as genuine fossils10, have recently been downgraded by some workers11 to the status of artefacts produced by entirely non-biological processes. To have a chance of success, it seems that the search for remnants of earliest life must be carried out on sedimentary rocks that are as old, unmetamorphosed, unmetasomatized and undeformed as possible. That remains easier said than done. For the time being, the many claims for life in the first 2.0–2.5 billion years of Earth's history are once again being vigorously debated: true consensus for life's existence seems to be reached only with the bacterial fossils of the 1.9-billion-year-old Gunflint Formation of Ontario12.

There's another, potentially more serious, problem with using isotope ratios as evidence of early life. Gérard et al. (2009) have recently documented the presence of modern bacteria in drillcore samples of rocks that are 2.7 billion years old. They detected trace amounts of ribosomal RNA that were sufficient to identify more that ten diverse species of bacteria living in these subsurface formations.

If modern bacteria can invade and colonize ancient rocks then it's highly likely that more ancient bacteria can also live in ancient rocks. Over the course of millions of years, these colonizers can leave traces of organic molecules. But those molecules do not show that life existed in those places at the time when the rocks were formed. In other words, just because you have "light" organic molecules in rocks that are billions of years old does not mean that the cells that created those molecules lived billions of years ago.

The conclusion of the Gérard et al. (2009) paper is worth quoting,

Our results strongly suggest that contemporary bacteria inhabit what are generally considered exceptionally well-preserved subsurface Archaean fossil stromatolites of the Hamersley Basin, Western Australia. They are possibly in very low numbers, their distribution confined to microfractures where water may circulate (perhaps only intermittently), and their metabolic activities might be extremely low. However, upon geological timescales spanning 2.7 Gy, even such low cell numbers must have contributed significantly to the pool of biogenic signatures associated to these rocks, including microfossils, biological isotopic fractionation and lipid biomarkers. Although our results do not necessarily invalidate previous analyses, they cautiously question the interpretation of ancient biomarkers or other life traces associated to old rocks, even pristine, as syngenetic biogenic remains when bulk analyses are carried out.

What does all this tell us about early life? It tells us that the evidence for life before 3 billion years ago is being challenged in the scientific literature. You can no longer assume that life existed that early in the history of Earth. It may have, but it would be irresponsible to put such a claim in the textbooks without a note of caution.

What else does this story tell us? It tells us something about how science is communicated to the general public. The claims of early life were widely reported in the media. Every new discovery of trace fossils and trace molecules was breathlessly reported in countless newspapers and magazines. Nobody hears about the follow-up studies that casts doubt on those claims. Nobody hears about the scientists who were heroes in the past but seem less-than-heroic today.

That's a shame because that's how science really works. That's why science is so much fun.

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Brasier, M.D., Green, O.R., Jephcoat, A.P., Kleppe, A.K., Van Kranendonk, M.J., Lindsay, J.F., Steele, A., and Grassineau, N.V. (2002) Questioning the evidence for Earth's oldest fossils. Nature 416::76-81. [PubMed]

Dalton, R. (2002) Microfossils: Squaring up over ancient life. Nature 417:782-784. [doi:10.1038/417782a]

Fedo, C.M., Whitehouse, M.J. and Kamber, B.S. (2006) Geological constraints on detecting the earliest life on Earth: a perspective from the Early Archaean (older than 3.7 Gyr) of southwest Greenland. Phil. Trans. R. Soc. B 361:851-867. [doi: 10.1098/rstb.2006.1836]

Gérard, E., Moreira, D., Philippot, P., Van Kranendonk, M.J., and López-García, P. (2009) Modern Subsurface Bacteria in Pristine 2.7 Ga-Old Fossil Stromatolite Drillcore Samples from the Fortescue Group, Western Australia. PLoS ONE 4: e5298. [doi:10.1371/journal.pone.0005298]

Pinti, F.L., Mineau, R., and Clement, V. (2009) Hydrothermal alteration and microfossil artefacts of the 3,465-million-year-old Apex chert. Nature Geoscience 2:640-643. [doi: 10.1038/ngeo601]

Schopf, J.W. (1993) Microfossils of the Early Archean Apex chert: new evidence of the antiquity of life. Science 260:640-646. [PubMed]

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Gérard, E., Moreira, D., Philippot, P., Van Kranendonk, M., & López-García, P. (2009). Modern Subsurface Bacteria in Pristine 2.7 Ga-Old Fossil Stromatolite Drillcore Samples from the Fortescue Group, Western Australia PLoS ONE, 4 (4) DOI: 10.1371/journal.pone.0005298

Pinti, D., Mineau, R., & Clement, V. (2009). Hydrothermal alteration and microfossil artefacts of the 3,465-million-year-old Apex chert Nature Geoscience, 2 (9), 640-643 DOI: 10.1038/ngeo601

Human Y Chromosome Mutation Rates

 
One thing men are really good at is making mistakes—just ask any woman. When it comes to mutations we are ten times better than women at ensuring the evolution of the species.

Knowing the actual rate of mutation in humans—or any other species—is important for many reasons. For one thing, it tells us about the maximum possible rate of evolution. For another, it gives us an important clue about the differences between beneficial, detrimental, and neutral alleles.

It's a lot more difficult to measure mutation rates than you might imagine. In theory, you could sequence the genomes of hundreds of parents and their offspring and identify mutations that must have occurred in the germ lines of the parents. In practice, this is far too expensive and time-consuming and, besides, it will miss any severely detrimental mutations.

But let's say you did the experiment in spite of the time and money. If the measured mutation rate turned out to be close to the calculated value, then you could assume that most of the mutations were neutral. A few might be beneficial.

Another possibility is to measure the number of differences between two individuals who are separated by a large number of generations. In this case you are measuring the combined effect of mutation and the fixation of alleles in a population. This is what we do whenever we compare gene sequences from different species.

Alleles can be fixed by natural selection or by random genetic drift. If most are fixed by natural selection (adaptation) then you'll learn very little about the overall mutation rate aside from a minimum estimate. That's because you don't know the fitness of every allele and how fast it became fixed in the population and you don't know how many mutations were detrimental or neutral, and what happened to them.

Calculating the rate of evolution in terms of nucleotide substitutions seems to give a value so high that many of the mutations must be neutral ones.

Motoo Kimura (1968)
However, you have a fighting chance if most mutations give rise to neutral alleles. In that case, the overall rate of fixation by random genetic drift is the same as the mutation rate [see: Random Genetic Drift and Population Size]. The data suggest that this is the correct scenario. When we compare individual genes from different species, the observed differences are consistent with the expected result if most of the differences are due to the fixation of neutral alleles by random genetic drift.

For the comparison between humans and chimpanzees, the estimated rates are remarkably consistent. They range from about 2 × 10^-8 to about 5 × 10^-8 mutations per nucleotide (base pair) per generation (Nachman, 2004; Britten, 2002). This agrees with the known error rate of DNA replication, which is about 10^-10 per nucleotide per replication. Since there are about 400 DNA replications between the male zygote and mature sperm, this translates to 4 × 10^-8 mutations per nucleotide per generation [see, Mutation Rates].

This is where men come in. There are many fewer cell divisions in the female line—about 30—so the egg contributes fewer mutations than the sperm. In fact, for most purposes we can ignore women in these calculations. Men have another big advantage. They have a Y chromosomes that's passed down directly from father to son and it doesn't recombine with any female chromosomes.¹ You don't need to worry about fixation.

If you sequence Y chromosomes from related men you can get a direct estimate of the mutation rate provided most of the alleles are neutral. It's best to choose men who are distantly related since there won't be many differences between closely related men. Two sons, for example, are likely to have identical Y chromosomes.

Xue et al. (2009) did the experiment [Human mutation rate revealed]. They sequenced the Y chromosomes of two men who were separated by 13 generations. After eliminating repetitive regions, the relevant region of comparison was 10.15 × 10⁶ nucleotides (base pairs, 10.15 Mb). The men differ at four confirmed sites. This gives a mutation rate of 3.0 × 10^-8 per generation or 0.75 × 10^-10 per nucleotide per DNA replication.

The agreement is remarkable. What this means is that we have a good handle on the mutation rate in humans and we have growing evidence that most mutations are neutral (i.e. most of our genome is junk).

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1. This isn't strictly correct but you can ignore the small regions where recombination is possible.

Britten, R.J. (2002) Divergence between samples of chimpanzee and human DNA sequences is 5%, counting indels. Proc. Nat. Acad. Sci. USA 99:13633-13635. [doi: 10.1073/pnas.172510699]

Nachman, M.W. (2004) Haldane and the first estimates of the human mutation rate. J Genet. 83:231-233. [PubMed]

Xue, Y., Wang, Q., Long, Q., Ng, B.L., Swerdlow, H., Burton, J., Skuce, C., Taylor, R., Abdellah, Z., Zhao, Y.; Asan, Macarthur, D.G., Quail, M.A., Carter, N.P., Yang, H., Tyler-Smith, C. (2009) Human Y Chromosome Base-Substitution Mutation Rate Measured by Direct Sequencing in a Deep-Rooting Pedigree. Curr Biol. Aug 26. [Epub ahead of print] [doi: 10.1016/j.cub.2009.07.032]

Xue, Y., Wang, Q., Long, Q., Ng, B., Swerdlow, H., Burton, J., Skuce, C., Taylor, R., Abdellah, Z., & Zhao, Y. (2009). Human Y Chromosome Base-Substitution Mutation Rate Measured by Direct Sequencing in a Deep-Rooting Pedigree Current Biology DOI: 10.1016/j.cub.2009.07.032

Proof of Special Creation

 
I'm sure many of you were troubled by the argument of Rev. William A. Williams who wrote The Evolution of Man Scientifically Disproved. As I explained in a previous posting, Rev. Williams has proved by mathematics that evolution cannot account for the current population of the Earth. There should be 2 × 10³⁷³ people if evolution is true [The Evolution of Man Scientifically Disproved].

We take comfort in the fact that this disproof is not widely known. But that's about to change. A reader¹ alerted me to a YouTube video where a renowned Mathematics Professor explains the disproof in a manner that any creationist idiot can understand.

Now that it's on YouTube, everyone's going to know about it. Evolution is in big trouble.

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1. Thank-you.

Monday's Molecule #134

 
Today's "molecule" isn't a molecule. I'm looking for the technique that's illustrated by the example shown here. Describe the technique and identify the Nobel Laureates who discovered it.

The first person to identify the technique and the Nobel Laureates, wins a free lunch. Previous winners are ineligible for six weeks from the time they first won the prize.

There are only two ineligible candidates for this week's reward: Alex Ling of the University of Toronto, and Markus-Frederik Bohn of the Lehrstuhl für Biotechnik in Erlangen, Germany.

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.

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

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The image is taken from this website on paper chromatography.

Get a Ph.D.!!!

 
I already have a degree but for those of you who don't, here's a golden opportunity.

Now you can get real degree just in 4-5 weeks on base of your professional experience

We will get your self a verifiable degree of:
Masters, Bachelors and PhD

Ring right now

1.305.460.5721

Leave your msg, with your full name and number and we will get back to you shortly.

I think it refers to science and engineering degrees. English doesn't seem likely to be one of the eligible categories for Ph.D. studies.

I don't know why it takes so long to get a Bachelor or a Masters degree. Surely you can do it in less time than it takes to get a Ph.D.? Maybe it's cheaper to get a B.Sc. or an M.Sc. The email message didn't mention anything about the cost of the degrees—I'm guessing it would be about 30,000 rubles.

The "personal experience" part is intriguing. Ms. Sandwalk wants to know if you can get a Ph.D. for 35 years of putting up with Ph.D.'s. And I want to know if you can get one for 35 years of putting up with ....... never mind.

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