Translation at CSH

 
My co-author, Marc Perry, is at the Cold Spring Harbor Laboratories on Long Island (NY, USA). He sent me this photograph. I think it may be a Henry Moore.

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This Book Don't Need Reviews

 
Book Description (from Dembski at Uncommon Descent):

Although atheism might have been logically tenable before Darwin, writes Richard Dawkins, Darwin made it possible to be an intellectually fulfilled atheist. This little book shows that atheism must seek intellectual fulfillment elsewhere decisively demonstrating the need for intelligence in explaining life’s origin. This is the best overview of why traditional origin-of-life research has crashed and burned and why intelligent design is necessary to explain the high-tech engineering inside the cell.

Author William A. Dembski worked closely as an advisor with the producers of the Spring 2008 documentary Expelled: No Intelligence Allowed starring Ben Stein. How to Be an Intellectually Fulfilled Atheist (Or Not) is the intellectual argument that helped inform significant elements of the movie. This controversial feature-length documentary film about researchers, professors, and academics who claim to have been marginalized, silenced, or threatened with academic expulsion because of their challenges to some or all parts of Darwin’s theory of evolution is one of the top twelve highest grossing documentary’s of all time. It has attracted both praise and controversy in its challenge against Darwinism.

If you liked the previous books by Jonathan Wells and William Dembski then you'll love this one. If you didn't, then you won't.

Did he really say "Ben Stein" and "intellectual argument" in the same sentence?

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Junk DNA Opponents Are at It Again

 
Nils Reinton has just posted a provocative piece on Sciphu entitled Hammering nails in the “junk-DNA” coffin. Here's what he says,

Below you will find a list of references that I hope will contribute to the fall of the term “junk-DNA“, - some of it may (currently) lack a known function, but it is not junk !!!

Disclaimer: This is a list of useful references when arguing against the common overestimation of the amount of “junk”-DNA. By listing these I am not claiming anything beyond what I have already posted on this blog or in a comment somewhere. Also and importantly, I have not myself had the time to review these articles as thoroughly as I would have wanted to, - some have been read carefully, others lightly and yet others just skimmed through. Thus, you are more than welcome to comment on these references if you have opinions on any of them, or find them unsuited for this list.

You are more than welcome to visit Sciphu and make comments. I can't be bothered.

The articles are just the same-old, same-old, litany of occasional discoveries of functional bits of DNA coupled with a fanatical belief in the biological significance of every single transcript that has ever been reported in the literature.

Oh yes, I almost forgot. Nils also throws in some papers about the number of binding sites for transcription factors. I guess he hasn't read any of my postings on the importance of non-specific binding [see Transcription Factors Bind Thousands of Active and Inactive Regions in the Drosophila Blastoderm].

THEME

Genomes & Junk DNA

Total Junk so far

    54%
I think there's good reason to assume that up to 90% of our genomes consist of junk DNA where the word "junk" means that it does not have a biological function. I haven't been able to keep up my series of postings analyzing the human genome but so far there's very good reason to believe that more than half is junk.

I've never seen an anti-junkie address the genetic load argument. Has anyone else? I wonder how they think we can survive if a substantial amount of our DNA is essential?

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Schizophyllum commune Has 28,000 Distinct Sexes

 
This is the Botany Photo of the Day from The University of British Columbia Botanical Garden and Centre for Plant Research. The organism is the fungus Schizophyllum commune which is reported to have 28,000 sexes according to Tom Volk's Fungus of the Month for February 2000. Check out the Botany Photo of the Day blog for a much better picture.

In some parts of the world sex is legally restricted to arrangements involving single members of specified gender. I wonder which sexes of Schizophyllum commune would qualify? Personally, I think that members of sex 408 should be allowed to marry members of sex 12,105 but all other marriages are immoral and should be illegal.

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Definitions Matter: Negative Selection and Postive Selection

 
In recent issues of the Proceedings of the National Academy of Sciences (USA) we have an interesting example of misuse of a key term in evolution.

The paper in question is by Sun et al. (2008a) of the University of California, San Francisco. The title of the paper is important: "Experimental evidence for negative selection in the evolution of a Yersinia pestis pseudogene." Here's how they describe this negative selection in the abstract,

Yersinia pestis, the agent of bubonic plague, evolved from the enteric pathogen Yersinia pseudotuberculosis within the past 20,000 years. Because ancestor and descendant both exist, it is possible to infer steps in molecular evolution by direct experimental approaches. The Y. pestis life cycle includes establishment of a biofilm within its vector, the flea. Although Y. pseudotuberculosis makes biofilms in other environments, it fails to do so in the insect. We show that rcsA, a negative regulator of biofilms that is functional in Y. pseudotuberculosis, is a pseudogene in Y. pestis. Replacement of the pseudogene with the functional Y. pseudotuberculosis rcsA allele strongly represses biofilm formation and essentially abolishes flea biofilms. The conversion of rcsA to a pseudogene during Y. pestis evolution, therefore, was a case of negative selection rather than neutral genetic drift.

Hmmm ... something about this form of "negative selection" seems puzzling. Does anyone see what it is?

The article was published online on June 3, 2008 and appeared in the June 10, 2008 issue of PNAS. It was communicated by National Academy member Stanley Falkow of Stanford University.

In this week's issue (Oct. 21, 2008) we see a letter from Jianzhi Zhang of the Department of Ecology and Evolutionary Biology, University of Michigan (Zhang, 2008).

There are two types of natural selection in biological evolution: Positive (Darwinian) selection promotes the spread of beneficial alleles, and negative (or purifying) selection hinders the spread of deleterious alleles (1). Pseudogenization is normally detrimental and prevented by negative selection. However, changes in genetic background or environment may render a formerly useful gene worthless, leading to the relaxation of the negative selection. Consequently, mutations disrupting the gene are fixed by genetic drift, and the gene becomes a pseudogene. This is the common type of pseudogenization by neutral evolution. Sometimes, however, a previously useful gene may become harmful to an organism. In this case, mutations destroying the gene would be beneficial and would be fixed by positive selection. Thus, pseudogenization can be adaptive (2). Recently, Sun et al. (3) reported an excellent example of adaptive pseudogenization, convincingly demonstrating that gene loss can also serve as an “engine” of evolution (4). Nevertheless, instead of calling it “positive selection,” they mistakenly used “negative selection.” The case involves Yersinia pestis, the agent of bubonic plague that is frequently transmitted by fleas. The authors found that the rcsA gene of Y. pestis became a pseudogene in the last 20,000 years (3). Replacing the rcsA pseudogene with its functional version represses the formation of biofilms in fleas (3), which would reduce the transmission rate of the bacteria. That is, the pseudogenization of rcsA allowed the formation of Y. pestis biofilms, which enhances the transmission of the bacteria, and hence was likely driven by positive selection.

That looks like a pretty devastating criticism to me. I'm convinced that the title of the paper was inaccurate. They were publishing an example of positive selection and not negative selection as claimed.

The authors replied in the same issue (Sun et al., 2008b).

In our article (1) we used “negative selection” to succinctly convey that a previously functional allele became deleterious and therefore was removed by natural selection. However, Zhang (2) is correct that our usage was contrary to the usual meaning. Olson's term, “adaptive gene loss” (3), would have been more appropriate. We are gratified that Zhang agrees with our conclusion that the pseudogenization of rcsA was adaptive.

Translation: "We really screwed up."

How did this happen? Normally, before a paper is published the work is presented at meetings and in lab group meetings. Was there nobody who recognized that the authors were using the wrong term? Clearly the authors themselves (all three) never questioned what they were putting into the title. Clearly the person who communicated the article didn't either, and neither did any of the reviewers.

What's happening to science these days? Now, don't get me wrong. These sorts of things happened in the "olden days" as well but I'm convinced that the problem is much more serious today. There is too much stuff being published that should never have made it past the lab group, let alone past reviewers.

Here's a question for everyone who has read this far. What should be done with the original paper? The title is wrong. How do we alert people to the fact that the authors have agreed that they made an error?

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Sun, Y-C., Hinnebusch, J.B. and Darby, C. (2008a) Experimental evidence for negative selection in the evolution of a Yersinia pestis pseudogene. Proc. Natl. Acad. Sci. (USA) 105:8097-8101. [DOI: 10.1073/pnas.0803525105]

Sun, Y-C., Hinnebusch, J.B. and Darby, C. (2008b) Reply to Zhang: Adaptive gene loss in Yersinia pestis rcsA pseudogenization. Proc. Natl. Acad. Sci. (USA) 105:E70; published ahead of print October 15, 2008. [doi:10.1073/pnas.0807434105]

Zhang, J. (2008) Positive selection, not negative selection, in the pseudogenization of rcsA in Yersinia pestis. Proc. Natl. Acad. Sci. (USA) 105:E69; published ahead of print October 15, 2008 [doi:10.1073/pnas.0806419105]

Guns and Kids Don't Mix

 
From an Associated Press report: Boy, 8, shoots himself to death at Mass. gun show.

WESTFIELD, Mass. (AP) — With an instructor watching, an 8-year-old boy at a gun fair aimed an Uzi at a pumpkin and pulled the trigger as his dad reached for a camera.

It was his first time shooting a fully automatic machine gun, and the recoil of the weapon was too much for him. He lost control and fatally shooting himself in the head.

I'm mostly interested in the comment further down in the press release.

"This accident was truly a mystery to me," said Bizilj, director of emergency medicine at Johnson Memorial Hospital in Stafford, Conn. "This is a horrible event, a horrible travesty, and I really don't know why it happened."

Canadian Cynic says exactly what we all must be thinking.

Yeah, it's a puzzler, all right. A real stumper. Children and fully automatic weapons -- what could possibly go wrong?

This is why I love Canadian Cynic!

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A Rainy Day in Toronto

 
The large white building is part of the MaRS complex of research buildings. It houses the labs of my colleagues who are based in the Hospital Research Institutes. Many of them are in my Department. I wonder if a pot of gold has appeared in one of their offices?

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Gene Genie #39

 
The 39th edition of Gene Genie has been posted at Genetics & Health [Gene Genie #39: Personal genomics, health and evolution].

Welcome to the 39th edition of Gene Genie, the carnival of clinical genetics and personalized medicine.

Personalized genomics are all over the news lately, so let’s jump right and see what’s going on.

The beautiful logo was created by Ricardo at My Biotech Life.

The purpose of this carnival is to highlight the genetics of one particular species, Homo sapiens.

Here are all the previous editions .....

1. Scienceroll
2. Sciencesque
3. Genetics and Health
4. Sandwalk
5. Neurophilosophy
6. Scienceroll
7. Gene Sherpa
8. Eye on DNA
9. DNA Direct Talk
10. Genomicron
11. Med Journal Watch
12. My Biotech Life
13. The Genetic Genealogist
14. MicrobiologyBytes
15. Cancer Genetics
16. Neurophilosophy
17. The Gene Sherpa
18. Eye on DNA
19. Scienceroll
20. Bitesize Bio
21. BabyLab
22. Sandwalk
23. Scienceroll
24. biomarker-driven mental health 2.0
25. The Gene Sherpa
26. Sciencebase
27. DNA Direct Talk
28. Greg Laden’s Blog
29. My Biotech Life
30. Gene Expression
31. Adaptive Complexity
32. Highlight Health
33. Neurophilosophy
34. ScienceRoll
35. Microbiology Bytes
36. Human Genetic Disordrs
37. The Genetic Genealogist
38. ScienceRoll
39. Genetics & Health

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The Spaghetti Harvest

 
The Spaghetti Harvest in Switzerland was first broadcast by the BBC on April 1, 1957. I'm old enough to have seen it on television in 1957—it was on the The Tonight Show with Jack Parr [On This Day].



I'm not sure that you could broadcast something like this today in North America. Most people wouldn't understand. New Scientist lists it as one of Seven of the greatest scientific hoaxes.

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Monday's Molecule #94

 
Most of you should recognize this molecule. You must describe both parts of the molecule, making sure to state clearly what you are seeing. As an extra challenge, you have to specifically mention something that is not shown even though it might be normally considered part of the complex.

It's a short step from there to this week's Nobel Laureate(s) but you need to be careful. There are two possible answers and one of them has already been chosen. You have to pick the other one.

The first one to correctly identify the molecule and name the Nobel Laureate(s), wins a free lunch at the Faculty Club. Previous winners are ineligible for one month from the time they first collected the prize. There are three ineligible candidates for this week's reward: Alex Ling of the University of Toronto, Haruhiko Ishii, and Bill Chaney of the University of Nebraska.

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 and names the Nobel Laureate(s). Note that I'm not going to repeat Nobel Laureate(s) 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. I reserve the right to select multiple winners if several people get it right.

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

UPDATE: Several people recognized that the molecule is a nucleosome. The figure on the left show the conformation of the histone core consisting of histones H2A, H2B, H3 and H4. The figure on the right shows the same protein core (rotated) with DNA wrapped around it to form the nucleosome core particle. The fifth histone, H1, is part of the linker region and it isn't shown.

Nobody guessed the Noel Laureate. It is Albrecht Kossel. There is no winner this week.

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Final Notice: PZ Myers in Toronto and Guelph

 
The Center for Inquiry, Toronto and The University of Toronto Secular Alliance are sponsoring a lecture by PZ Myers this Friday evening (Halloween). Contact me if you want to meet PZ.

From the CFI press release ...

Fri, Oct 31, 2008, 7:30pm at University of Toronto, J.J.R. MacLeod Auditorium. A catered reception with PZ exclusively for Friends of the Centre will take place from 6:00 - 7:00 pm at the Centre For Inquiry.

Partnered with the University of Toronto Secular Alliance the Centre for Inquiry - Ontario presents the popular biologist and author of the stimulating blog Pharyngula. Dr. Myers is an associate professor of biology at the University of Minnesota, Morris. He obtained his B.S in zoology from the university of Washington and his Ph.D. in biology from the Institute of Neuroscience, University of Oregon. His blog is the most widely read science blog on the internet with topics ranging from octopus, religion and getting kicked out of Expelled.

Note:  On Sat, Nov 1, 2008, 2-4pm Guelph Campus Skeptics will host a more informal interactive discussion with PZ Myers at the University of Guelph, A.A. Thornbrough Building, Rm. 1200 (click THRN on the map). There will be refreshments available from 1 - 2pm. The cost is $3 and free for members of CFI.

PZ Myers Presents: Science Education: caught in the middle of the war between science and religion

Friday, October 31, 7:30 pm - 9:30 pm
MacLeod Auditorium
2158-1 King's College Circle,
Room 2158, Toronto, ON, M5S1A8

See the PZ Myers Visit website for more information, including how to get tickets and how to get to the MacLeod Auditorium.

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Chris Nedin Enters the Blogosphere

 
Chris Nedin is an interrupted paleontologist who studied Ediacaran and Early Cambrian palaeontology, palaeoecology and taphonomy. He was one of the early regulars on the newsgroup talk.origins and he even came to a Howlerfest in Toronto a few years ago (1997).¹ (Chris lives in Australia.)

Chris Nedin has now become a blogger. Visit Ediacaran and read his first posting: The Spandrels of San Marco and the Anomalocaris Paradigm. Here's a teaser ..

The Spandrels of San Marco and the Panglossian Paradigm is one of my favourite science papers. As someone who accepts natural selection as a powerful evolutionary mechanism, but who considers that there are other, equally, or perhaps more, powerful mechanism out there, such as genetic drift, this paper resonated a lot with me. To summarise the paper (if you haven’t read it, please do), not everything that happens in evolution occurs because it was selected for. Like spandrels, things can happen as a consequence of other events. To summarise the summary, sh*t happens.

Here I’d like to develop that theme using Anomalocarus.

Welcome to the blogosphere, Chris. With an opening like that, we expect big things in the future.

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1. I still remember how excited he and Saint Andrew (Andrew MacRae) were when the curators at the Royal Ontario Museum pulled out their famous fossil of Anomalocarus to look at. Chris and Andrew, being paleontologists, were the only ones allowed to touch it. Chris was also thrilled to see the trilobites with bite marks. Read his posting to see why.

What Does Marcus Antonius Tell Us about Evolution?

 
Meet my (probably mythical)¹ ancestor, Marcus Antonius (83 BC - 30 BC), better known as Mark Antony. (Color photo not available.)

Mark Antony was a friend, and cousin, of Gaius Julius Caesar, although after Caesar's assassination he stopped praising Caesar. Mark Antony had a falling out with Octavian (Augustus) after the Second Triumvirate split up and he ended up in Egypt. The history is kind of interesting but not very relevant.

We're mostly concerned about Mark Antony's genes. Near the end of his life he had three children by Cleopatra, Queen of Egypt; the twins Alexander Helios & Cleopatra Selene II and Ptolemy Philadelphus. This led to gene flow between the Italians and subpopulations in the Middle East. (There were other liaisons that contributed to gene flow in both directions between the Middle East and Europe.)

Before moving to Egypt, Mark had several wives in Rome. One of them was Octavia Major and they had a daughter, Antonia Minor. Antonia married Nero Claudius Drusus Germanicus and one of her sons was Claudius Cæsar (Tiberius Claudius Nero Germanicus), Emperor of Rome. At the time Antonia and Drusus were living in Lugdunum (Lyon, France).

Claudius married Valeria Messalina (granddaughter of Octavia) and their daughter was Genvissa (Venus Julia). Claudius then married Julia Agripina and had more children, including Emperor Nero. We aren't interested in Julia Agripina except to note her scientific contribution to the understanding of eukarotic transcription [Mushrooms for Dinner].

Genvisa married Arviragus, King of Siluria, in 45 AD. Siluria was a kingdom in the south of Wales and at the time they were resisting Roman occupation. Arviragus became King of the Britons. Their son was Meric (Marius) , King of the Britons. Do you see where this is headed?

Meric married Penardun and their son was Coel I "Old King", King of Siluria. Coel had a SON who in turn had an unnamed GRANDSON who had a daughter named Alofe (Aife).

Alofe married Fiachadh III Streabhruine, 120th Ard Righ of Ireland, and their son was Muirreadhach Tireach , King of Connought, 122nd Ard Righ of Ireland.

Muirreadhach married Murien and their son was Eochaidh Moihmeodhain (Echu Mugmedón), 124th Ard Righ of Ireland.

Eochaidh married Carthan Casduff and their son was Niall Nóigiallach - Niall of the Nine Hostages, my ancestor and the ancestor of about 100 million other people.

Thus, Marcus Antonius is also my ancestor.

The figure below show that the various subpopulations within Europe are genetically distinct (Novembre et al. 2008). See my recent posting, Genes and Geography with a link to Razib's explanation of the structure of populations at Gene Expression [Genetic map of Europe; genes vary as a function of distance].

This data represents only a small percentage of the genetic variation in Europeans. Much of the remaining variation does not show a geographic distribution like the one in the figure because the variants arose much earlier. They have had time to spread to all subpopulations, or perhaps they pre-date the founding of the European population.

Novembre et al. also had to restrict their analysis to those 1,387 individuals who had both sets of grandparents from the same region. Many of the remaining group of 1,805 individuals did not know where their grandparents were born but a substantial number had grandparents from two different regions. What this means is that there is substantial ongoing gene flow between the various subpopulations

What does this have to do with Mark Antony? Quite a bit, actually. Looking at the figure from the Nature paper one can't help but be struck by what it says about population structure and gene flow in the past. The pink individuals in the upper left-hand have clearly been partially isolated from the rest of the European population for quite some time—equivalent to about 40-60 generations.

We know that this group has received alleles from Italy via Mark Antony and Niall of the Nine Hostages and probably from a great many other Italians who were living in Roman Britain. This level of gene flow amounts to just a trickle and the foreign alleles might easily be diluted out by random genetic drift.

We can think of gene flow in the opposite direction by considering what might have happened if a favorable allele had arisen in the Irish population about 1500 years ago. While it might have spread rapidly in Ireland, chance are it would not have made much impression in the rest of the European subpopulations until very recently. All bets are off now that humans have become so mobile but it is worth keeping in mind that the populations of most other species probably look a lot like ours did only a few centuries ago.

New beneficial alleles will not make much headway in 2000 years because gene flow between subpopulations is very low. There's no reason to assume that it was any different in the ancient past—it may even have been worse. Think about that the next time you hear about some hypothetical allele that arose 50,000 years ago and became fixed in the entire species. That's not very likely.

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1. See comments. It looks like Genvissa, the presumed daughter of Claudius, is a mythical character made up many centuries after her presumed marriage to the King of the Siluria.

Novembre J, Johnson T, Bryc K, Kutalik Z, Boyko AR, Auton A, Indap A, King KS, Bergmann S, Nelson MR, Stephens M, Bustamante CD (2008) Genes mirror geography within Europe. Nature, Published online 31 August 2008 [doi:10.1038/nature07331]

Niall Nóigiallach - Niall of the Nine Hostages

 
Niall Nóigiallach is a very famous man (Nóigiallach is Gaelic for "having Nine Hostages"). He was an Irish King who lived from about 350 to 405 AD. The "nine hostages" refers to hostages that he kept from each of the places that owed him allegiance.

Niall was fond of raiding the coast of Roman Britain and on one of those raids he captured a man named Maewyn Succat, who became a slave in Ireland. Succat eventually escaped, returned to Britain, and became a Christian missionary. He then went back to Ireland to convert the Irish heathens to Christianity. We know Maewyn Succat by his Christian name, Patrick, or Saint Patrick.

The reason Niall Nóigiallach is famous is because he is associated with the List of High Kings of Ireland, one of the oldest well-established genealogies in all of Europe. Anybody who connects to the lineage can trace ancestors back to about 100 AD.

Niall is also famous for another reason. DNA studies indicate that one in twelve Irish men carry a Y chromosome haplotype that traces back to Niall. The haplotype is also common in Scotland and England, and on the continent. This makes Niall one of only a handful of men who have millions of direct male descendants. (Genghis Khan was another [Genghis Khan a Prolific Lover, DNA Data Implies].)

Families that trace their ancestry back to Niall of the Nine Hostages include: (O')Neill, (O')Gallagher, (O')Boyle, (O')Doherty, O'Donnell, Connor, Cannon, Bradley, O'Reilly, Flynn, (Mc)Kee, Campbell, Devlin, Donnelly, Egan, Gormley, Hynes, McCaul, McGovern, McLoughlin, McManus, McMenamin, Molloy, O'Kane, O'Rourke and Quinn.

My mother's maiden name is Doherty. We are descendants of the O'Dochartaigh's of Donegal in the north-west part Ireland. Donegal is in the Republic of Ireland not in the part of Ulster that became what is now called "Northern Ireland", which is part of the United Kingdom. Donegal is near where the most intense spot on the DNA map is located.

My mother was hoping to establish the direct connection between her ancestors and the ancient lineage leading to Niall but it hasn't been possible. That was a big disappointment because I thought it would be fun to have a known ancestor from 400 AD.

Recently I discovered that my ancestors connect to the Niall lineage through English and through Scottish lines that are completely unrelated to the Doherty's. This shows, once again, that most people in England, Scotland, and Ireland are related if you go back far enough. The fact that so many lineages connect to the Niall lineage is not as significant as you might think. It's mostly because that ancient lineage is so well known.

In my case, the connections come through Isabel de Clare, grandmother of Robert the Bruce of Scotland, and through Isabel Mar, the wife of Robert the Bruce. Niall Nóigiallach is one of my ancestors.

If your ancestors are from the British Isles, chances are pretty high that we are related if we go back 60 generations. We all have about a trillion potential ancestors back then but that's five orders of magnitude more than all the people who lived in the British Isles at that time.

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Happy Mole Day!

 
Today is "Mole Day," celebrated as part of National Chemistry Week. You can read all about it on Adventures in Ethics and Science [Happy Mole Day! (What's a mole?)].

What do you mean, "it's not that kind of mole?"¹

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1. What would you call 6.02 × 10²³ Cindy Crawford moles?