Some Good News to Start the Year

With two weeks remaining in winter, the season about to end has been actually been pretty good to us with the exception of the record-breaking 28″ dump last month.  I can start by congratulating Josh Michener for landing an NRSA postdoctoral fellowship (and for his PNAS paper that emerged from his graduate work with Christina Smolke).  It has also been quite nice to see four more papers surface from the lab in the last two months.  The first one came out in  Molecular Biology and Evolution and describes work by my former postdoc, Deepa Agashe (now running her own lab at the National Centre for Biological Sciences in Bangalore, India), who looked at the selective pressures acting upon codon bias.  She systematically varied codon throughout a highly-expressed methylotrophy gene in Methylobacterium extorquens AM1, generating seven synonymous variants to compare to the wild-type coding sequence.  Remarkably, the selective effects we report were massive, including that the “perfect gene” comprised of exclusively the most frequently-used codons expressed very little protein and led to extremely low fitness.  Thanks to our collaborators Allan Drummond (now at University of Chicago) and Ceci Martinez-Gomez (Lidstrom lab, U. Washington) for their great help.  The second was a project from the lab of Chuck Davis (Harvard) in PLoS Genetics that I contributed to in terms of thinking about the parallels between horizontal gene transfer in bacteria and what they have observed between the mitochondrial DNA of a parasitic plant and its host.  The third is a Primer I wrote for PLoS Biology that discusses just how much of ecology or evolution can be detected from metagenomic sequencing.  A major goal of the paper was to frame an excellent paper in the same issue from Matt Herron and Michael Doebeli that examined adaptive diversification in a two resource environment.  Finally, the fourth just came out today as a Highlighted Paper in this month’s issue of Genetics.  This describes work by my former graduate student, Miki Lee (now a postdoc in the lab of Jiandong Huang at the University of Hong Kong).  Early in her thesis she discovered that a surprising kind of beneficial mutation – the integration of an introduced plasmid into the host genome – occurred many times in each of eight evolving populations.  During a five month post-defense mini-postdoc, one of the things she did (besides co-develop FREQ-Seq) was to follow-up on her old results and put together a fascinating story of clonal interference between simultaneous versions of this type of mutation (not to mention everything else going on).  She detected waves of up to 17 similar (but distinguishable) alleles all rising and falling in the same population, only sometimes ( 3 of 8 ) being fortunate enough to give rise to the eventual winning lineage.  Adaptation is not simple, but it is undoubtedly amazing in the outcome and the process.

Advertisements is a Go!

Today – Darwin’s 204th birthday – we are happy to “launch” in a more public way  Thanks to the excellent work of Chris Engles, the site has been up and running, and I have finally managed to take the time to gather enough material from pestering a few colleagues that the point of the site will hopefully be somewhat clear.  We have recently added some new syllabi (from Jonathan ArnoldJohn McCutcheonPaul Turner, and Joshua Weitz) and a project designed by Joshua to use a models to study population dynamics that ensue due to CRISPR-mediated host-phage interactions.  We have also begun to expand our list of “Investigators” that we hope will give interested students (and PIs) a clearer view of who is in the field.  If you are missing please let us know; we have only made it part way through our list from an initial brainstorming.  So I hope you enjoy seeing what your other colleagues have put into place, and please consider sharing some of your own.  Cheers,

Latest News:

Remarkably, three more months have gone by since my last post.  We have crowned a new Ph.D. from the lab, Dr. Nigel Delaney, back on 30 October.  He gave a fantastic presentation concentrating on his new work estimating the distribution of fitness effects of successful mutations for one of our strains of Methylobacterium.  He has now gotten started at his new position at the Broad Institute working with Vamsi Mootha
We’ve also seen two new papers come out, both including Nigel, in fact.  The first of these describes ‘Clarity‘, an open-source program to manage lab automation that he worked on with Jose Rojas Echenique.  We’ve used this to run our automated, robotic growth analysis system, but it could be applied to any given automation challenge.
Second, we have published a paper describing ‘FREQ-Seq’, a new method to rapidly determine allele frequencies directly from mixed populations.  Developed by Lon Chubiz and Miki Lee, this is an efficient way to barcode samples and shine the light of Illumina sequencing on just known sites of interest, thereby generating phenomenal depth of coverage (~150,000x for 100 samples in 3% of a lane) and avoiding any typical Illumina library prep.  The bridging primers with barcodes for this can be regenerated from a panel of plasmids available through the non-profit plasmid distribution organization,  Nigel developed a software program, ‘FREQout‘, that allows users to rapidly extract frequency information from the Illumina data.  We sent this to Yousif Shamoo’s lab for testing and they’ve completed all the data they needed for part of their paper in press at PNAS in the very first go.

End of Summer Update.

In the past month and a half we’ve had four new papers come out. First is one led by myself and Stephane Vuilleumier in Journal of Bacteriology announcing the genome sequences of six strains of Methylobacterium. Second, Hsuan-Chao Chiu, his then-mentor Daniel Segre and I have a follow-up to last year’s Science paper in Proceedings of the Royal Society B that extends some general theory that considers how epistasis arises from the dependence of fitness upon underlying traits. Third, David Robinson and Miki Lee (former undergrad and grad student, respectively) led a paper that came out in Nucleic Acids Research describing a new program (OASIS) for automated annotation of transposable elements from genome sequences and some surprising findings regarding their distribution. Finally, Nick Leiby and Will Harcombe worked to report in BMC Evolutionary Biology that a few of the Lenski long-term E. colipopulations have become dependent upon citrate for growth on glucose.

Comings and Goings, Grants, and Publications.

In the midst of a busy summer, we have had some comings, goings, new grant, and a new paper. We welcome Sherif Gerges as a visiting summer undergrad and Josh Michener as a new postdoc, fresh off his Caltech Ph.D. Unfortunately we had to give our best wishes to a few departing lab members: postdocs Jessi Purswani (headed back to Valencia for a postdoc) and Alex Bradley (starting off his new lab at Wash. U.), and lab manager/technician extraordinaire Maryska Kaczmarek (heading off to study Evolution for her Ph.D. at UT Austin). Speaking of UT Austin, a proposal led by Claus Wilke to the Army Research Office there has been awarded. His lab, ours, and six others are looking to see if we can make a statistical association between growth conditions and cellular composition. Should be a fun challenge! Finally, a new paper of mine has been accepted that describes an accidental, surprising finding of mine a few years ago. Some of the replicate populations I initiated didn’t grow to full density from single colonies that I used to start each one, and they started to crash. Most of them recovered after a few cycles but one population remained alive but >100 times lower density than the others. It turns out that it specifically adapted to life at low density and lost fitness at standard densities.

Publication: “Diminishing Returns Epistasis Among Beneficial Mutations Decelerates Adaptation.”

 3 June, 2011 – Our paper uncovering a generic trend for diminishing returns between beneficial mutations was published in today’s issue of Science.  Besides an excellent perspective in the same issue by Kryazhimskiy et al. on our paper and that of our colleague, Tim Cooper (U. Houston), reporting the same finding in E. coli, stories were also written in Science NewsGenomeWeb Daily NewsHarvard Gazette, and University of Houston.

New Website, New Publications.

At long last, we have done a make-over of our website.  In terms of scientific output, since the Science paper last mentioned as news nearly a year ago, we’ve had publications in Cell (a Preview about a great paper from the group of Sander Tans), Cell Reports (David Chou uncovered a remarkable diversity of genetic pathways to parallel optimization of gene expression), and two papers in PLoS Genetics (one led by Nigel Delaney describing the incredibly fast evolution of Mycoplasma following a host shift, and a second by Miki Lee describing the repeated, advantageous loss of massive chunks of the Methylobacterium genome).  Furthermore, the Cell Reports paper was featured in a podcast by Cell Press (starting ~18 minutes in).  Finally, Chris conceived of and hosted a rather entertaining outreach activity: a Microbial Sciences Initiative-hosted seminar/beer tasting by Sam Calagione, founder of Dogfish Head Craft Brewery in Milton, DE.  Thanks to the hard work of Karen Lachmayr in organizing it for MSI, Sam’s presentation and kegs of four outstanding beers that were served to 300 people in the packed house it was a most excellent evening in celebration of the powers of microbes.  The video is available online; beer must be provided separately.