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Tuesday, April 07, 2009

On the Evolution of Bacterial Chromosomes

 

This is a story about two cultures; the old biologists who grew up with the 'phage group and bacterial genetics, and the younger biologists who didn't.

It's also a story about science journalism and the reporting of science in the 21st century.

We've known about plasmids in bacteria for a very long time. Plasmids are small circular DNA molecules that carry a number of genes, such as those for antibiotic resistance, or sex. Some of them are present in multiple copies while others are present in only a single copy. In the case of single-copy plasmids, their replication is coupled to that of the chromosome and the daughter plasmids segregate to the daughter cells just like the newly replicated chromosomes do.

Genes can hop from chromosomes to plasmids and back again. This phenomenon was discovered in the 1950's by Jacob and Adelberg (1959). Several well-known plasmids carrying certain chromosomal genes were studied, including a famous one known as F-lac—an F plasmid containing the lac operon.

By the time the first E. coli Bible was published in 1987, there were dozens and dozens of examples of gene transfer between chromosomes and plasmids (Holloway and Low, 1987).

During the 1970s and 80s, the DNA contents of many difference species of bacteria were published. It soon became apparent that certain classes of bacteria (e.g. Rhizobiaceae) contained large plasmids called megaplasmids. Sometimes it was difficult to tell the difference between a plasmid and a chromosome (bacterial chromosomes are usually circular).

As a general rule, plasmids were dispensable. The bacteria could be "cured" of a plasmid and still survive. When the plasmid acquired essential genes, as they did from time to time, they became chromosomes. Some species of bacteria had two or more chromosomes. It was part of general knowledge that plasmids could evolve into chromosomes as described in a 1998 review by Moreno.
Animal intracellular Proteobacteria of the alpha subclass without plasmids and containing one or more chromosomes are phylogenetically entwined with opportunistic, plant-associated, chemoautotrophic and photosynthetic alpha Proteobacteria possessing one or more chromosomes and plasmids. Local variations in open environments, such as soil, water, manure, gut systems and the external surfaces of plants and animals, may have selected alpha Proteobacteria with extensive metabolic alternatives, broad genetic diversity, and more flexible and larger genomes with ability for horizontal gene flux. On the contrary, the constant and isolated animal cellular milieu selected heterotrophic alpha Proteobacteria with smaller genomes without plasmids and reduced genetic diversity as compared to their plant-associated and phototrophic relatives. The characteristics and genome sizes in the extant species suggest that a second chromosome could have evolved from megaplasmids which acquired housekeeping genes. Consequently, the genomes of the animal cell-associated Proteobacteria evolved through reductions of the larger genomes of chemoautotrophic ancestors and became rich in adenosine and thymidine, as compared to the genomes of their ancestors. Genome organisation and phylogenetic ancestor-descendent relationships between extant bacteria of closely related genera and within the same monophyletic genus and species suggest that some strains have undergone transition from two chromosomes to a single replicon. It is proposed that as long as the essential information is correctly expressed, the presence of one or more chromosomes within the same genus or species is the result of contingency. Genetic drift in clonal bacteria, such as animal cell-associated alpha Proteobacteria, would depend almost exclusively on mutation and internal genetic rearrangement processes. Alternatively, genomic variations in reticulate bacteria, such as many intestinal and plant cell-associated Proteobacteria, will depend not only on these processes, but also on their genetic interactions with other bacterial strains.
Given this context, I was interested in a recent press release: Evolutionary origin of bacterial chromosomes revealed. "Hmmm," I thought., "I wonder what new mechanism has been discovered?"

Imagine my surprise to read ...
Most bacteria have only one chromosome. The Rhizobiaceae is an unusual bacterial family in that all of its members have either two chromosomes or one chromosome and very large plasmids. Until this study, it was not clear how such multichromosomal architectures had evolved.

João Setubal, associate professor at the Virginia Bioinformatics Institute and the Department of Computer Science at Virginia Tech, commented: "Thanks to the efforts of the Agrobacterium Genome Sequence Consortium and the wider research community, we have sufficient sequence data available from different bacterial species to allow the inference of a general model for bacterial genome evolution. It appears that the transfer of genes from chromosomes to large plasmids mediates second chromosome formation."
That's not new. The idea that large megaplasmids in Rhizobiaceae could become plasmids by acquiring essential genes has been around for three decades, at least. Surely these workers known their history? The press release must be an exaggeration of what's in the paper.

So I looked up the paper (Slater et al., 2009). These workers sequenced the genomes of a number of related bacterial species containing chromosomes and plasmids. They announce the "surprising" discovery that genes can transfer between chromosomes and plasmids.
While it has long been known that gene transfer can occur between organisms, the picture that emerges from our study shows a group characterized by composite genomes in which genes of all classes are not only migrating between organisms, but also intracellularly among chromosomal and plasmid replicons.
It sounds like they never heard of F-lac or any of the other F′ or R′ plasmids. It sounds like they are completely unaware to the fact that transfer of genes from chromosomes to plasmids is an old established fact.

The authors propose a "general model for bacterial genome evolution" in which plasmids evolve into chromosomes.

This is not an isolated phenomenon. There seem to be lots of cases where today's scientists are unaware of the history of their field. A consequence of this ignorance is that the wheel is being constantly reinvented, with all the associated hype of a modern breakthrough.

Another example is the recent "discovery" of regulatory RNAs. Bacterial and 'phage examples have been known for forty years.

Why is this happening? Why do reviewers let it pass?


[Image Credit: Jessica Snyder Sachs]

Holloway, B. and Low, K.B. (1987) F-Prime and R-Prome Factors. in Escherichia coli and Salmonella typhimurium: Cellular and Molecular Biology. F.C. Neidhardt ed. vol.2.

Jacob, F. and Adelberg, E.A. (1959) Transfer of Genetic Characters by Incorporation in the Sex Factor of Escherichia coli. Comptes Rendus 249:189-191.

Moreno, E. (1998) Genome evolution within the alpha Proteobacteria: why do some bacteria not possess plasmids and others exhibit more than one different chromosome? FEMS Microbiol 22(4):255-275. [PubMed]

Slater, S.C., Goldman, B.S., Goodner, B., Setubal, J.C., Farrand, S.K., Nester, E.W., Burr, T.J., Banta, L., Dickerman, A.W., Paulsen, I., Otten, L., Suen, G., Welch, R., Almeida, N.F., Arnold, F., Burton, O.T., Du, Z., Ewing, A., Godsy, E., Heisel, S., Houmiel, K.L., Jhaveri, J., Lu, J., Miller, N.M., Norton, S., Chen, Q., Phoolcharoen, W., Ohlin, V., Ondrusek, D., Pride, N., Stricklin, S.L., Sun, J., Wheeler, C,, Wilson, L,, Zhu, H., and Wood, D.W. (2009) Genome Sequences of Three Agrobacterium Biovars Help Elucidate the Evolution of Multi-Chromosome Genomes in Bacteria. J. Bacteriol. 2009 Feb 27. [Epub ahead of print] [PubMed] [DOI: 10.1128/JB.01779-08]



How to Prevent Evolution in Mosquitos

 
A paper in PLoS Biology discusses How to Make Evolution-Proof Insecticides for Malaria Control. The idea is to develop drugs that only kill mosquitoes after they've reproduced. That way the population can't evolve resistance to the drug.

What's interesting about this paper is the response of two different bloggers. On adaptationist, Jerry Coyne's blog, guest writer Matthew Cobb thinks it's a great idea [Of mosquitoes and the menopause]. In fact he links his discussion of the paper to the well-known adaptationist explanation of menopause.

The pluralist, Ryan Gregory, is much more skeptical, pointing out that evolution is smarter than you are ["Evolution-proof"?].

Grab your popcorn and enjoy the fight. My money's on Gregory.


Monday's Molecule #116: Winners

 
UPDATE:The photographs of the mouse embryos are from a paper by Kothary et al. (1989). This was a study where a lacZ (β-galactosidase) gene under the control of a strong, ubiquitously competent promoter was introduced into mouse zygotes. When the gene was induced (right) the presence of β-galactosidase was detected by a blue color assay. The foreign gene is induced in almost every tissue.

These sorts of experiments in construction of transgenic mice were later extended by the work of Nobel Lauteates Mario Capecchi, Martin Evans, and Oliver Smithies who developed techniques for using embryonic stem cells.

Several people guessed the Nobel Laureates but only two people provided an explanation of the "molecule." Dima Klenchin, who is ineligible, was the only one to pick up on the hint and find the 1989 paper.

The winner is Shumona De of Dalhousie University.



If you look closely you'll realize that these mouse embryos aren't really "molecules" in any meaningful sense of the word "molecule." That doesn't matter 'cause I still want you to identify what's going on here. This is the first time that I've resorted to using photographs from my previous life—shows you how desperate I'm getting!

The images are supposed to remind you of the work of some Nobel Laureates. See if you can guess who they are.

The first person to identify the photographs and the Nobel Laureates wins a free lunch at the Faculty Club. Previous winners are ineligible for one month from the time they first won the prize.

There are eight ineligible candidates for this week's reward: David Schuller of Cornell University, Adam Santoro of the University of Toronto, Dima Klenchin from the university of Wisconsin, Alex Ling from the University of Toronto, Bill Chaney of the University of Nebraska, Elvis Cela from the University of Toronto, Peter Horwich from Dalhousie University, and Devin Trudeau from the University of Toronto.

Dima and Bill have donated their free lunch to a deserving undergraduate so I'm going to continue to award an additional free lunch 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 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.


Kothary, R., Clapoff, S., Darling, S., Perry, M.D., Moran, L.A., Rossant, J. (1989) Inducible expression of an hsp68-lacZ hybrid gene in transgenic mice. Development. 105:707-14. [PDF]

Applying to NSERC? Everyone gets a grant!

 
According to a study done by Richard Gordon and Bryan J. Poulin, Cost of the NSERC Science Grant Peer Review System Exceeds the Cost of Giving Every Qualified Researcher a Baseline Grant. (NSERC is Canada's funding agency for non-medical science research.)
Using Natural Science and Engineering Research Council Canada (NSERC) statistics, we show that the $40,000 (Canadian) cost of preparation for a grant application and rejection by peer review in 2007 exceeded that of giving every qualified investigator a direct baseline discovery grant of $30,000 (average grant). This means the Canadian Federal Government could institute direct grants for 100% of qualified applicants for the same money. We anticipate that the net result would be more and better research since more research would be conducted at the critical idea or discovery stage. Control of quality is assured through university hiring, promotion and tenure proceedings, journal reviews of submitted work, and the patent process, whose collective scrutiny far exceeds that of grant peer review. The greater efficiency in use of grant funds and increased innovation with baseline funding would provide a means of achieving the goals of the recent Canadian Value for Money and Accountability Review. We suggest that developing countries could leapfrog ahead by adopting from the start science grant systems that encourage innovation.
This sounds like a good idea to me. Thanks to Bora Zivkovic of A Blog Around the Clock for finding the paper.


Royal Protocol

 
Ever country has a protocol officer and part of their job is to specify how one is supposed to treat the Head of State. In America, for example, you must always refer to the President as Mr. President and unelected cabinet ministers are addressed as Mr./Madam Secretary [Office of the Chief of Protocol].

Visiting Heads of State are expected to conform to American protocol and when the President visits another country he is expected to conform to their rules of protocol. That's how international diplomacy works. It's a system that has evolved over several centuries to try and makes things easier when two different countries communicate. The idea is for countries to respect each other.

Postdiluvian at The Unexamined Life doesn't think that Americans need to respect the protocols and traditions of a foreign country [Is it OK to hug the Queen?]. Now, as it turns out, Michelle's hug was a breach of protocol but not that big a deal, even in England. It would be comparable to someone forgetting to say "Mr. President" when addressing Barack Obama.

That doesn't justify this kind of response ....
Now here’s the bottom line: you can have your “Queen” as a powerless (and utterly pointless) figurehead if you like. She can even keep her massive wealth that somehow came into her family’s possession over the centuries. But if you ever start this bullshit about “Royal Protocol” again, or whether or not it’s okay for people to touch her, you will be removing yourself from the realm of the Serious and joining the realm of Laughingstock, much like the concept of Monarchy did ages ago.
Americans often wonder why they have so much trouble making friends in "foreign" countries. I can't imagine why.


Monday, April 06, 2009

Five Against One

 
It's sounds so unfair. Four Christians against one lone atheist. If you add in the moderator it's five against one.

But the atheist is Christopher Hitchens so they didn't have a chance.1

Next time they should try half a dozen Christians—and they should look for ones that are smart.2

Christian Book Expo 2009



1. Actually, if you watch the "debate" you'll realize that Hitchens didn't need to do or say anything. Every single one of their arguments for the existence of God has been refuted dozens of times. It's like a kindergarten class in Christian apologetics. Most of the time I wish Hitchens had kept his mouth shut.

2. Assuming that ....

[Hat Tip: Friendly Atheist]

What Is Epigenetics?

 
Berger et al. (2009) attempt to define epigenetics.
"An epigenetic trait is a stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence."
Sounds good to me. Just about anything wold be better than the kitchem sink definition proposed by Eva Jablonka [Epigenetics at SEED].

The main examples are "DNA methylation, histone modifications, histone variants, and nucleosome positioning." These are chromosomal alterations that are passed on to daughter cells following cell division by mitosis or meiosis.

Although the Berger et al. don't mention it, these epigenetic signals are all reversible. I still don't find the term useful. It's far more accurate to refer to each of the individual examples by name and the field is "regulation of gene expression."


Berger, S.L., Kouzarides, T., Shiekhattar, R., and Shilatifard, A. (2009) An operational definition of epigenetics. Genes & Dev. 23:781-783. [DOI: 10.1101/gad.1787609]

[Hat Tip: Hopeful Monster]

Monday's Molecule #116

 
If you look closely you'll realize that these mouse embryos aren't really "molecules" in any meaningful sense of the word "molecule." That doesn't matter 'cause I still want you to identify what's going on here. This is the first time that I've resorted to using photographs from my previous life—shows you how desperate I'm getting!

The images are supposed to remind you of the work of some Nobel Laureates. See if you can guess who they are.

The first person to identify the photographs and the Nobel Laureates wins a free lunch at the Faculty Club. Previous winners are ineligible for one month from the time they first won the prize.

There are eight ineligible candidates for this week's reward: David Schuller of Cornell University, Adam Santoro of the University of Toronto, Dima Klenchin from the university of Wisconsin, Alex Ling from the University of Toronto, Bill Chaney of the University of Nebraska, Elvis Cela from the University of Toronto, Paul Horwich from Dalhousie University, and Devin Trudeau from the University of Toronto.

Dima and Bill have donated their free lunch to a deserving undergraduate so I'm going to continue to award an additional free lunch 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 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.


Sunday, April 05, 2009

Religion Wars: Linux and Mac vs. Rationalism

 
Greg Linux is disappointed that the Confliker virus didn't do more damage on April 1st [Did Conflicker Flop? Yes. Why? Nobody knows].

I wasn't worried because I checked all five of my computers and not one them were infected. If they had been, it was very easy to get rid of the worm. My Linux machine didn't have the worm either.

That doesn't stop Greg from offering this advice ...
Experts expect that the worm is going to re-awaken at some time in the future and possibly actually do something. In the mean time, you may want to get rid of it if is on your system.

If you run Windows, the best way to get rid of the computer is to get a Mac or a Linux computer. There are probably other ways to do this but I don't really care. If you are running Linux, this worm can't directly affect you.
Sheesh, those religious nuts sure can be silly.


The End of Christian America?

 
The number of Americans who don't identify with a religion has increased from 8% in 1990 to 15% today. This is encouraging but it doesn't quite mean that the battle between rationalism and superstition has been won.

Nevertheless, the fact that a national magazine could publish an article like "The End of Christian America" is an indication that the debate is on.

If North American societies become much less religious—like those in Europe—then most of the major problems with creationism will go away. Maybe then we can concentrate on promoting good science education. That's why some of us would rather put our efforts into promoting rationalism over superstition rather than defending specific creationist attacks on schools.

Both approaches are needed but those who advocate the compatibility of science and superstition are not helping.


[Hat Tip: Hemant Mehta who has some interesting comment.]

Last Week's Scientific Breakthroughs

 
This are stories from the past week that would make good topics for discussion. I don't have time so I'll leave it up to you.
Scientists Find 'Baffling' Link between Autism and Vinyl Flooring

Masturbation could bring hay fever relief for men

New research shows lower educational outcomes for survivors of childhood cancer

6 out of every 10 university students present mathematical anxiety or fear of this subject

Humanoid Robot Helps Scientists To Understand Intelligence

Omega-3 kills cancer cells

How probiotics can prevent disease

UBC study first to show evolution's impact on ecosystems

UT Southwestern researchers reveal how the brain processes important information

Your oral health is connected to your overall health

Penn researchers demonstrate a new model for drug discovery with a fluorescent anesthetic

Humans May Be Losers If Technological Nature Replaces The Real Thing, Psychologists Warn

Milkshakes Are Medicine For Anorexic Teens In Family-based Outpatient Therapy

Hermit Arthropods 500 Million Years Ago?

Alzheimer's Disease Linked To Mitochondrial Damage

Robot Scientist Becomes First Machine To Discover New Scientific Knowledge

Virus-built Battery Could Power Cars, Electronic Devices

Athletic Ability May Lie in a Single Gene


Washington D.C.

 
In a few days I'll be on my way to Washington (Bethesda, actually) to attend the Center for Inquiry World Congress 2009. Let me know if you'll be there and we can meet up.

Here are the main events ....

Thursday April 9, evening: Panel: The Influence of Darwin

Friday April 10, afternoon: Science and Public Policy

Friday April 10, 5:45pm: James Randi: Search for the Chimera

Saturday April 11, morning: Skepticism and Science

Saturday April 11, 5pm: Special Feature: Separation of Church and State

Sunday April 12, morning: Secularism Around the World