Saturday, October 24, 2015

Intelligent design needs to clean up its act if it expects to be taken seriously

Jonathan McLatchie tried to make the case that ID is different from creationism in two recent videos on a Christian apologetics podcast [see Jonathan McLatchie says that intelligent design is a science and Jonathan McLatchie explains the difference between intelligent design and creationism].

I think there's some serious attempts to do science among ID proponents but I also think it's bad science. It's fun, informative, and challenging to debate real science with knowledgeable, informed members of the ID community.

However, that same community embraces many, many advocates who are not knowledgeable about evolution and not informed about how science works. They are not scientists by any stretch of the imagination but they pretend to be scientific. Many of them are Young Earth Creationists who seriously think that the universe was created pretty much as it is only 6000 years ago. While it's true that every ID proponent is a creationist (i.e believes in the existence of a supernatural creator) there are some versions of creationism that are more irrational than others.

The theistic evolution version of creationism rejects the views of their anti-science YEC friends but Intelligent Design Creationism embraces all comers as long as they are vehemently opposed to materialism and evolution. That's fine, but then ID can't claim to be scientific. You can't have your cake and eat it too. Either you try to act like scientists, in which case you have to oppose the kooks and YECs in your movement, or you admit that you are a religious and social movement, in which case you stop pretending to be a science.

I hope that the knowledgeable, informed, members of the ID community will abandon the ridiculous path they've taken where they try to make a scientific case for ID knowing full well that the majority of their supporters disagree strongly with their premises (e.g. common descent). That's an untenable position.

We've seen recently that some ID proponents are attempting to do this. I'm thinking of Jonathan McLatchie and Vincent Torley right now but there are others. How is it working out? Look at the Torley post on Uncommon Descent where he's trying to explain evolution to IDiots: Human and chimp DNA: They really are about 98% similar. It's an uphill battle. The kooks are accusing him of becoming a Darwinist.

But that's exactly what the ID community needs to do in order to gain credibility. They need to shed the kooks and the IDiots who make them look silly. When they do that, they may find that more of us are willing to have a serious discussion about science.

David Klinghoffer is one of the names I mentioned in an earlier post when I identified leading ID proponents who have no clue about the science they are opposing. Others are Denyse O'Leary, Barry Arrington, Phillip Johnson, Casey Luskin,1 David Klinghoffer, Paul Nelson, John West, and William Lane Craig. These people represent the face of the ID movement and that's how we're going to judge Intelligent Design Creationism unless they clean up their act. (We also judge it by the people who post comments on blogs and Facebook and by those politicians who support it in the public sphere.)

Klinghoffer posts on Evolution News & Views (sic)—a site that doesn't allow comments. His latest post is a classic example of the problems that the ID movement faces: Here's Why We Answer Some of Our Less Cogent Critics.

As you can see, he avoids the issue I raised in favor of an ad hominem attack. Wouldn't it be nice to see a scientific debate between Michael Behe and David Klinghoffer on the meaning of evolution? Not going to happen as long as ID is primarily a religious movement.


1. Casey Luskin can't decide how old the universe is but he leans toward Young Earth Creationism. Yet he's a leading spokesman for the "science" of intelligent design.

Friday, October 23, 2015

Nature publishes a misleading history of the discovery of DNA repair

The history of DNA repair is well-known. Here's a quote from "Early days of DNA repair: discovery of nucleotide excision repair and homology-dependent recombinational repair" by W.D. Rupp in 2013 (Rupp, 2013).
This article describes events related to the first papers published in the 1960s describing nucleotide excision repair (NER) and homology-dependent recombinational repair.
Here's are the relevant papers.
Setlow, R.B., and Carrier, W.L. (1964) The disappearance of thymine dimers from DNA: An error-correcting mechanism. Proc. Natl. Acad. Sci. (USA) 51:226–231. [Full Text]

Boyce, R.P., Howard-Flanders, P. (1964) Release of ultraviolet light-induced thymine dimers from DNA in E. coli K-12. Proc. Natl. Acad. Sci. (USA) 51:293–300. [Full Text]

Pettijohn, D, and Hanawalt, P. (1964) Evidence for repair-replication of ultraviolet damaged DNA in bacteria. J. Mol. Biol. 9:395–410. [PubMed]

Thursday, October 22, 2015

Jonathan McLatchie says that intelligent design is a science

Here's another short podcast on a Christian apologetics show. Jonathan McLatchie is being asked whether intelligent design is a science.


Café Scientifique in Mississauga

Some of you might recall that I gave a presentation at a Café Scientifique in Mississauga (Ontario, Canada) [Café Scientifique]. It was a lot of fun and there were many interesting people at the meeting.

The new season continues on Monday, October 26h with a meeting at 7 pm at The Franklin House, 263 Queen St S., in Streetsville, Mississauga (Ontario Canada) [see Meetup]. Come and join us for a discussion about teaching critical thinking in Ontario schools. My friend Chris DiCarlo is the speaker.

Come hear TVO 2008 Best Lecturer winner Christopher DiCarlo talk about “Introducing Standard Critical Thinking Skills to Ontario High Schools”.

The topic follows Dr. DiCarlo's efforts over the last five years or so to personally lobby the Ministry of Education and various School Boards in an effort to start a pilot project which introduces both teachers and students to the value of basic Critical Thinking skills. The Pilot Project began in September, 2014 with the Upper Grand District School Board. The first year of the project was a great success. It is now entering its 2nd phase which involves the development of video footage and written materials for Learning Modules which will be made available to all teachers throughout Ontario and eventually, Canada. These modules can be used for any grades, though they are intended for grades 9 and 10 in order to introduce these skills as early as possible in High School. The eventual plan also includes the development of a stand-alone course for Grade 12.

Dr. Christopher DiCarlo is a philosopher, educator, and author. He currently teaches in the Faculties of Philosophy at the University of Toronto and Ryerson University. He is also a lifetime member of Humanist Canada and an Expert Advisor for the Centre for Inquiry Canada.

He has been invited to speak at numerous national and international conferences and written many scholarly papers ranging from bioethics to cognitive evolution. His latest book entitled: How to Become a Really Good Pain in the Ass: A Critical Thinker’s Guide to Asking the Right Questions was released worldwide by Prometheus Press in August, 2011 and is currently in its fifth printing and is a best-seller in the U.S.

He is currently working on his latest book tentatively entitled: Flying Without A Pilot: A Determined Look at the Future of Ethics, Law, and the Value of Human Behavior.

In April, 2008 he was awarded TV Ontario’s Big Ideas Best Lecturer in Ontario Award for his lecture “The Relations of Natural Systems”.

In August, 2008, he was honoured with the Canadian Humanist of the Year Award from the Humanist Association of Canada.

Dr. DiCarlo is the Director of Critical Thinking Solutions, a consulting business for individuals, corporations, and not-for-profits in both the private and public sectors. He is also the developer of the first Pilot Project in Canada to introduce Standardized Critical Thinking skills into the Ontario Public High School curriculum which has begun in the Upper Grand District School Board.


Wednesday, October 21, 2015

The quality of the modern scientific literature leaves much to be desired

Lately I've been reading a lot of papers on genomes and I've discovered some really exceptional papers that discuss the existing scientific literature and put their studies in proper context. Unfortunately, these are the exceptions, not the rule.

I've discovered many more authors who seem to be ignorant of the scientific literature and far too willing to rely of the opinions of others instead of investigating for themselves. Many of these authors seem to be completely unaware of controversy and debate in the fields they are writing about. They act, and write, as if there was only one point of view worth considering, theirs.

How does this happen? It seems to me that it can only happen if they find themselves in an environment where skepticism and critical thinking are suppressed. Otherwise, how do you explain the way they write their papers? Are there no colleagues, post-docs, or graduate students who looked at the manuscript and pointed out the problems? Are there no referees who raised questions?

Tuesday, October 20, 2015

Jonathan McLatchie explains irreducible complexity

Listen to Jonathan McLatchie's explanation of irreducible complexity and why it represents a problem for the "neo-Darwinian paradigm." Keep in mind that he has been asked to do this by a Christian pastor on an Christian apologetics podcast. I wonder why?

McLatchie claims that an irreducibly complex system consist of a number of subfunctions where the removal of one subfunction renders the whole system nonfunctional. He implies that such systems can't be explained by evolution. Do all ID proponents agree? If we can show you a reasonable evolutionary explanation of the evolution of a single irreducibly complex system, using McLatchie's definition, would that refute his claim that such systems present a challenge to evolution? How about if we show you two examples? Three?



Vincent Torley and the genetic fallacy

Vincent Torley didn't like my post on Jonathan McLatchie's defense of ID [Jonathan McLatchie explains the difference between intelligent design and creationism]. Torley says that I have committed the sin of genetic fallacy [Larry Moran commits the genetic fallacy].

How terrible! Let's see if I can fix the problem.

To start, Vincent Torley says,
Because science is defined by its methodology, any attempt to discredit a field such as Intelligent Design by casting aspersions on the motives of its leading practitioners completely misses the point. No matter what their motives might be, the only question which is germane in this context is: do Intelligent Design researchers follow a proper scientific methodology, and do ID proponents support their arguments by appealing to that methodology? The answer to this question should be obvious to anyone who has read works such as Darwin’s Black Box, The Edge of Evolution, Signature in the Cell and Darwin’s Doubt. Intelligent Design researchers and advocates commonly appeal to empirical probabilities (which can be measured in the laboratory), mathematical calculations (about what chance and/or necessity can accomplish), and abductive reasoning about historical events (such as the Cambrian explosion) which bear the hallmarks of design.

Jonathan McLatchie explains the difference between intelligent design and creationism

This is a video from One Minute Apologist. Really, I'm not kidding. There actually is a man called Bobby Conway who is the One Minute Apologist.

He became a devout Christian when he was 19 and subsequently went off to Bible school then got a Doctorate of Ministry in Apologetics from Southern Evangelical Seminary. He's now a Ph.D. candidate in the Philosophy of Religion department at the University of Birmingham (UK). I'd love to be on his thesis committee but I'm not a philosopher. Maybe they'll invite John Wilkins to serve as external reviewer at the thesis defense?

The theme of his videos and website is ...
We provide quick, credible answers to apologetic questions that resource people with a hunger to defend their Christian faith.

Here's an interview with Jonathan McLatchie where McLatchie tires to pretend that ID is a legitimate scientific investigation that has nothing to do with creationism. Keep in mind that he's doing this while being interviewed by a Christian Pastor in a Christian apologetics video. Watch the video, it's only one minute.


Monday, October 19, 2015

Election Day in Canada: seat projections

The CBC poll-tracker website shows the Liberal Party in the lead with 37% of the vote. The Conservative Party is polling at 31% and the New Democratic Party trails at 22%.

In close elections it is extremely difficult to project those numbers into seats because there are many close races and the number of people sampled in each riding is quite small. Nevertheless, ThreeHundredEight and CBC have been making seat projections since the campaign began.

Here's the latest seat projections as of yesterday ...


If these projections are accurate then the Liberals will win the most seats but will be far short of a majority. Justin Trudeau will become the next Prime Minister of Canada and Stephen Harper will be gone.

The main uncertainty is voter turnout. A lot of Liberal voters are uncertain about who to vote for and many of them will be first-time voters, if they vote. The Conservative vote, on the other hand, is pretty solid and Conservative voters are very likely to vote today. Most of the Conservative vote is concentrated in rural ridings that are guaranteed wins for the Conservatives. It is still possible for the Conservatives to win enough close races to finish on top with the most seats.1

The NDP vote is soft and dropping. The biggest change in the past few days is the seat projections in Quebec where the NDP won 59 seats in the last election. (A big surprise.) As of today, CBC is projecting that they will only win 34 seats. All three of the other parties are projected to gain seats but the Liberals gain the most. The battle in Ontario was reduced several weeks ago to mainly a fight between Liberals and Conservatives. (There are a few ridings where the Liberals and NDP are neck-and-neck.)

It's interesting that the three-way race in British Columbia hasn't changed very much in a long time. The latest projections have the Conservatives slightly ahead with 16 seats to 13 for the Liberals and 12 for the NDP. (Plus one seat for the Green Party.) There are several scenarios where the overall winner will be decided by the vote in British Columbia. It could be a long night.

The result in the Greater Toronto Area (GTA) was decided weeks ago. The Liberals are going to capture almost all of the seats. The only secure victory for the Conservatives is Thornhill, and the only projected victory for the NDP is Toronto-Danforth. [See the interactive map at: ThreeHundredEight.] Olivia Chou is trailing badly in Spadina-Fort York.

In my area, Mississauga-Brampton, every seat is projected to go Liberal and many Conservative MPs are going down to defeat, including my own MP Bob Dechert. The NDP is not a factor in any of these ridings.


1. This does not mean that Harper will be able to hold on to power but it makes things complicated.

Election Day in Canada: popular vote predictions

The CBC poll-tracker website tracks a number of public opinion polls and calculates a weighted average. The latest numbers have the Liberal Party winning the most votes with the Conservative Party (current government) in second place.


This is a close election so normally you would have to take these numbers with a large grain of salt but the trend over the past month is pretty obvious.


There has been a steady decline in support for the New Democratic Party (NDP) and a steady increase in Liberal support. The percentage of people who say they will vote Conservative has not changed much. It would be truly astonishing if the actual results tonight are much different than the poll results in terms of total votes. (There could be a total collapse of the NDP vote but not a reversal of fortune.)


Friday, October 16, 2015

Human mutation rates

I was excited when I saw the cover of the Sept. 25th (2015) issue of Science because I'm very interested in human mutation rates. I figured there would have to be an article that discussed current views on the number of new mutations per generation even though I was certain that the focus would be on the medical relevance of mutations. I was right. There was one article that discussed germline mutations and the overall mutation rate.

The article by Shendure and Akay (2015) is the only one that addresses human mutation rates in any meaningful way. They begin their review with ...
Despite the exquisite molecular mechanisms that have evolved to replicate and repair DNA with high fidelity, mutations happen. Each human is estimated to carry on average ~60 de novo point mutations (with considerable variability among individuals) that arose in the germline of their parents (1–4). Consequently, across all seven billion humans, about 1011 germline mutations—well in excess of the number of nucleotides in the human genome—occurred in just the last generation (5). Furthermore, the number of somatic mutations that arise during development and throughout the lifetime of each individual human is potentially staggering, with proliferative tissues such as the intestinal epithelium expected to harbor a mutation at nearly every genomic site in at least one cell by the time an individual reaches the age of 60 (6).

Wednesday, October 14, 2015

"#For the King" nears the end of its Kickstarter campaign - add a Darwin statue!

My son's new game, For The King (#ForTheKing), is doing well on Kickstarter. So far they have over 3000 backers and over $120,000 [Kickstarter: For The King]. They met their launch goal within 24 hours and now they're closing in on the last defined stretch goal at $125,000 (balloons and highlands).

There's less than two days to go and the team [IronOak Games] has provided some incentive. Every time you post or tweet about For The King using the #ForTheKing hashtag your name will be put in a draw and the winning name will get a statue of him/her in the game.

If my name is chosen I'm going to ask for a statue of Charles Darwin. Help me get a stature of Darwin into the game by tweeting and posting #ForTheKing and promising to substitute Darwin for your own statue if you win.

video


Friday, October 09, 2015

Brace yourselves, a new "Icons" is coming

Having narrowly escaped one catastrophe—the end of the world on October 7th—there's another looming on the horizon. Denyse O'Leary tells us that Jonathan Wells is preparing an "update" of his book Icons of Evolution [What’s happened since Icons of Evolution (2002)?].

You know what's going to happen next year if she is right? We are going to deluged with pre-publication publicity promoting the book that we can't see. We'll be told that it refutes evolution and builds on the outstanding success of the first book. We'll be told that Jonathan Wells addresses and refutes all of the criticisms of his first book and adds some more devastating proofs that the Rev. Sun Myung Moon is right.

None of this will be true, of course, but that's why the IDiots will get in their licks before we can prove it by reading the book. This is the standard ploy taken by the Discovery Institute over the past few years.

I know a lot about Icons of Evolution because for seven years it was required reading in my course on critical thinking. All my students had to write essays on one of the chapters. They had to analyze the arguments that Wells was making and decide whether they were valid or not.

Some of you may have forgotten about Icons of Evolution so you may have to refresh your memory by reading the short summary and reviews on the Wikipedia site [Icons of Evolution]. You can see that Wells has his work cut out for him if he's going to reply to all of the criticism.

Here's a few posts that I have done over the years to show that Icons of Evolution is seriously flawed. Some of them show that Jonathan Wells is dishonest—something that my students usually discovered on their own.1
I'm hoping to get a response in his new book but I'm not holding my breath. I spent a lot of time showing that his last book, The Myth of Junk DNA was flawed but here's how Jonathan Wells responded [see Jonathan Wells Sends His Regrets] ...
Oh, one last thing: “paulmc” referred to an online review of my book by University of Toronto professor Larry Moran—a review that “paulmc” called both extensive and thorough. Well, saturation bombing is extensive and thorough, too. Although “paulmc” admitted to not having read more than the Preface to The Myth of Junk DNA, I have read Mr. Moran’s review, which is so driven by confused thinking and malicious misrepresentations of my work—not to mention personal insults—that addressing it would be like trying to reason with a lynch mob.
Denyse O'Leary warns us that there may be more "icons" in the next book. She quotes someone named Stephen Batzer who claims that there are three new "show stoppers."
  1. That Darwin’s finches are simply races of the same bird. There has been no speciation.
  2. That the tree of life is not viable. “It’s a bush!” they respond. Well, then Darwin was wrong, and the model is wrong. If it’s a *bush* it isn’t a *tree*. The Darwinian model is common descent and gradual differentiation. That has been shown to be false, because of #3.
  3. ORFAN (Orphan) genes. Where do novel genes come from? If common genes mean common descent, then novel genes mean intervention and an innovator.
I wish I were still teaching my course. These are so easy to refute that all my students would have gotten A's on their essays. It shows you that the level of biology expected by Denyse O'Leary and the IDiots is nowhere near as elevated as second year university.


1. Every year I would have students setting up an appointment to see me in my office to discuss a problem they were having with their essay. They had discovered that some things in Icons seemed inconsistent with the truth and they wondered where they were going wrong.

Wednesday, October 07, 2015

Nobel Prize for DNA repair

Tomas Lindahl, Paul Modrich, and Aziz Sancar shared the 2015 Nobel Prize in Chemistry for "for mechanistic studies of DNA repair" [Nobel Prize, Chemistry 2015].

Here's some of the press release.
In the early 1970s, scientists believed that DNA was an extremely stable molecule, but Tomas Lindahl demonstrated that DNA decays at a rate that ought to have made the development of life on Earth impossible. This insight led him to discover a molecular machinery, base excision repair, which constantly counteracts the collapse of our DNA.

Aziz Sancar has mapped nucleotide excision repair, the mechanism that cells use to repair UV damage to DNA. People born with defects in this repair system will develop skin cancer if they are exposed to sunlight. The cell also utilises nucleotide excision repair to correct defects caused by mutagenic substances, among other things.

Paul Modrich has demonstrated how the cell corrects errors that occur when DNA is replicated during cell division. This mechanism, mismatch repair, reduces the error frequency during DNA replication by about a thousandfold. Congenital defects in mismatch repair are known, for example, to cause a hereditary variant of colon cancer.
What about Phil Hanawalt?

Meanwhile, in other news: Discovery and Characterization of DNA Excision Repair Pathways: the Work of Philip Courtland Hanawalt ...
In 1963, Hanawalt and his first graduate student, David Pettijohn, observed an unusual density distribution of newly synthesized DNA during labeling with 5-bromouracil in UV-irradiated E. coli. These studies, along with the discovery of CPD excision by the Setlow and Paul Howard-Flanders groups, represented the co-discovery of nucleotide excision repair.
And Wikipedia [Philip Hanawalt] says,
Philip C. Hanawalt (born in Akron, Ohio in 1931) is an American biologist who discovered the process of repair replication of damaged DNA in 1963. He is also considered the co-discoverer of the ubiquitous process of DNA excision repair along with his mentor, Richard Setlow, and Paul Howard-Flanders. He holds the Dr. Morris Herzstein Professorship in the Department of Biology at Stanford University,[1] with a joint appointment in the Dermatology Department in Stanford University School of Medicine.
Here's what Hanawalt himself says about discovering DNA excision repair [The Awakening of DNA Repair at Yale] ...
Upon joining the faculty at Stanford University in late 1961 as Research Biophysicist and Lecturer, I returned to the problem of what UV did to DNA replication, now that we knew the principal photoproducts. I wanted to understand the behavior of replication forks upon encountering pyrimidine dimers, and I was hoping to catch a blocked replication fork at a dimer. Using density labeling with 5-bromouracil and radioactive labeling of newly-synthesized DNA, we were able to observe partially replicated DNA fragments in E. coli [13]. However, in samples from UV irradiated bacterial cultures, the density patterns of nascent DNA indicated that much of the observed synthesis was in very short stretches, too short to appreciably shift the density of the DNA fragments containing them [14]. I communicated these results to Setlow by phone and learned that he had just discovered that pyrimidine dimers in wild type cells, but not in Ruth Hill’s UV sensitive mutant, were released from the DNA into an acid soluble fraction. We speculated in discussion that my student, David Pettijohn, and I were detecting a patching step by which a process of repair replication might use the complementary DNA strand as template to fill the single-strand gaps remaining after the pyrimidine dimers had been removed. At about the same time, Paul Howard-Flanders in the Department of Therapeutic Radiology at Yale had isolated a number of UV-sensitive mutants from E. coli K12 strains, and he was able to show that these mutants were also deficient in removing pyrimidine dimers from their DNA. The seminal discovery of dimer excision was published by the Setlow and Howard-Flanders groups, as the first indication of an excision repair pathway [15,16]. Of course, the excision per se is not a repair event but only the first step, since it generates another lesion, the gap in one strand of the DNA. We carried out more controls, to then claim that we had discovered a non-conservative mode of repair replication, constituting the presumed patching step in the postulated excision-repair pathway [17]. I later showed that DNA containing the repair patches could undergo semiconservative replication with no remaining blockage [18].

Richard Boyce and Howard-Flanders at Yale also documented excision of lesions induced by mitomycin C in E. coli K12 strains, indicating some versatility of excision repair [19]. In a collaboration with Robert Haynes, I found a similar pattern of repair replication after nitrogen mustard exposure to that following UV, and we concluded that “it is not the precise nature of the base damage that is recognized, but rather some associated secondary structural alteration …” We speculated that “[s]uch a mechanism might even be able to detect accidental mispairing of bases after normal replication,” thus predicting the existence of a mismatch repair pathway [20]. Mismatch repair was reported by Wagner and Meselson a decade later [21] and yet another excision repair mode, termed base excision repair, was discovered by Tomas Lindahl [22].
One of Hanawalt's students was Jonathan Eisen [Tree of Life]. I'll be interested in hearing what he has to say about this Nobel Prize. It seems unfair to me.


Ten years after Dover - an excellent decade for Intelligent Design Creationism?

This month marks the tenth anniversary of the Kitzmiller v. Dover case in Pennsylvania [Tammy Kitzmiller, et al. v. Dover Area School District, et al.]. The legal victory will be celebrated by NCSE and Panda's Thumb and by many other supporters of science and evolution. If American law is your thing, then please join in the celebration of a legal victory.

It's much more interesting to evaluate whether the legal victory in Pennsylvania had any significant effect on the general public. Did it cause people to change their minds and abandon Intelligent Design Creationism to embrace science? Has America moved closer to the time when real science can be taught in the schools without interference from religion? Have politicians stopped trying to water down evolution in the public schools because of Judge Jones' decision in Kitzmiller v Dover? Have politicians stopped opposing evolution and has the public stopped voting for those who do?

Monday, October 05, 2015

Get a Job! - Department of Biochemistry, University of Toronto

This is my department [Department of Biochemistry]. Apply now!

Don't be fooled by the ad. Cutting edge biochemists can also apply.
Applications are invited for two Tenure-Stream Positions

The Department of Biochemistry at the University of Toronto invites applications for two tenure-stream appointments, at the rank of Assistant Professor. The appointments will commence on 1 July, 2016.

We seek candidates undertaking cutting edge research in cell, systems, molecular, or chemical biology. Technical knowledge including but not limited to metabolomics, synthetic biology, and structural biology (particularly, cryo-electron microscopy) that will complement our existing strengths would also be an asset.

Candidates must have a Ph.D. or equivalent in Biochemistry, Biophysics, Molecular Biology, Genetics, or a related discipline and have postdoctoral experience with an established record of excellence in research as demonstrated through a strong track record in publication. The successful candidates will be expected to mount an original and independently-funded research program at the highest international level and to publish articles in internationally recognized journals. The successful candidates must also demonstrate teaching excellence at the undergraduate and graduate levels through letters of reference. Salary will be commensurate with qualifications and experience.

The Department is one of the premier academic life sciences departments in North America, with 67 full-time faculty members and more than 200 graduate students and postdoctoral fellows.

All qualified candidates are invited to apply online by clicking on the link below. All application materials should be submitted online and include: 1) a detailed curriculum vitae; 2) a 3-5 page statement detailing research interests and objectives as well as potential teaching interests. We recommend combining documents into one or two files in PDF/MS Word format. Applicants should also arrange for three letters of reference commenting specifically on the applicant’s experience in teaching and research, to be sent directly to the department at chair.biochemistry@utoronto.ca by November 16, 2015.

Review of applications will begin on November 16, 2015, and applications will be accepted until the position is filled. Submission guidelines can be found at: http://uoft.me/how-to-apply. If you have questions about this position, please contact us at chair.biochemistry@utoronto.ca. For more information about the Department of Biochemistry, please visit http://biochemistry.utoronto.ca/.

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.

For further details and to apply online please visit https://utoronto.taleo.net/careersection/10050/jobdetail.ftl?job=1501211


Sunday, October 04, 2015

Genetic variation in human populations

The Human Genome Project produced a high quality reference genome that serves as a standard to measure genetic variation. Every new human genome that's sequenced can be compared with the reference genome to detect differences due to mutation. It's possible to build large databases of genetic variation by sequencing genomes from different populations. Genetic variation can be used to infer evolutionary history and to test theories of population genetics. Detailed maps of genetic variation can also be used to infer selection (genetic sweeps) and distinguish it from random genetic drift.

In addition to this basic science, the analysis of multiple human genomes can be used to map genetic disease loci through association of various haplotypes with disease. The technique is called genome wide association studies (GWAS). The same technology can be used to map other phenotypes to identify the genes responsible.

The 1000 Genomes Project Consortium has just published their latest efforts in a recent issue of Nature (Oct. 1, 2015) (The 1000 Genomes Project Consortium, 2015; Studmant et al., 2015). They looked at the genomes of 2,504 individuals from 26 different populations in Africa, East Asia, South Asia, Europe, and the Americas.


The idea is to identify variants that are segregating in humans. Single nucleotide polymorphisms (SNPS) are difficult to identify because the error rate of sequencing is significant. When comparing a new genome sequence to the reference genome you don't know whether a single base change is due to sequencing error or a genuine variant unless you have a high quality sequence. Most of the 2,504 genome sequences are not of sufficiently high quality to be certain that the false positive rate is low but by sequencing multiple genomes it becomes feasible to identify variants that are shared by more that one individual within a population.

Recall that every human genome has about 100 new mutations so that even brothers and sisters will differ at 200 sites. The 1000 Genomes Consortium looks at the frequency of alleles in a population to determine whether the genetic variation is significant. They use a preliminary cutoff of 0.5%, which means that a variant (mutation) has to be present in 5 out of 1000 genomes in order to count as a variant that's segregating within the population. They estimate that 95% of SNPs meeting this threshold are true variants. For small insertions and deletions the accuracy is about 80%.

For variants at lower frequency, additional sequencing to a depth of >30X coverage was done and the putative variant was compared against other databases of genetic variation. The predicted accuracy of variants at 0.1% frequency is about 75%.

Given those limitations, the results of the studies are very informative. Looking at single base pair changes and small indels (insertions and deletions), the typical human genome (yours and mine) differs from the standard reference genome at about 4.5 million sites. That's about 0.14% of our genomes. Humans and chimpanzees differ by about 1.4% or ten times more.

SNPs and small indels account for 99.9% of variants. The others are "structural variants" consisting of; large deletions, copy number variants, Alu insertions, LINE L1 insertions, other transposon insertions, mitochondrial DNA insertions (NUMTS), and inversions. The typical human genome has about 2,300 of these structural variants of which about 1000 are large deletions.

Most of these variants are in junk DNA regions but the typical human genome carries about 10-12,000 variants that affect the sequence of a protein. Many of these will be neutral and some of the ones that have a detrimental effects will be heterozygous and recessive. The average person has 24-30 variants that are associated with genetic disease. (These are known detrimental alleles. If you get your genome sequenced, you will learn that you carry about 30 harmful alleles that you can pass on to your children.)

The Consortium reports that the the typical genome has variants at about 500,000 sites mapping to untranslated regions of mRNA (UTRs), insulators, enhancers, and transcription factor binding sites. I assume they are using the ENCODE data here so we need to take it with a large grain of salt. Most of these sites are not biologically relevant.

As expected, common variants are distributed in populations all over the world. These are the result of mutations that arose several hundred thousand years ago and reached significant frequencies before the present-day populations separated. However, 86% of all variants are restricted to a single continental group. These are the result of mutations that occurred after the present-day populations split.

The African populations contain more genetic variation than the Asian and European populations. Again, this is is expected since the European and Asian groups split from within the African group after Africans had been evolving on that continent for thousands of years. The differences are not great—Africans differ at about 4.3 million SNPs while the typical Europeans and Asian differ at only 3.5 million SNPs.

Only a small number of loci show evidence of selective sweeps, or recent selection (adaptation). It indicates that most of the differences between local ethnic groups are not associated with adaptation. The exceptions are SLC24A5 (skin pigmentation), HERC2 (eye color), LCT (lactose tolerance), and FADS (fat metabolism).


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The Genomes Project Consortium (2015) A global reference for human genetic variation. Nature, 526(7571), 68-74. [doi: 10.1038/nature15393]

Thursday, October 01, 2015

How many RNA molecules per cell are needed for function?

One of the issues in the junk DNA wars is the importance of all those RNAs that are detected in sensitive assays. About 90% of the human genome is complementary to RNAs that are made at some time in some tissue or other. Does this pervasive transcription mean that most of the genome is functional or are most of these transcripts just background noise due to accidental transcription?