The past month and a half have seen several pieces of good news:
1. Will Harcombe’s paper just came out in PLoS Computational Biology. We are both extremely relieved and proud to have gotten this out, as it represents the first direct test ever as to whether central metabolic fluxes actually evolve to become optimal, as proposed by flux balance analysis. The answer is yes and no; strains that were already close to the optimum (for yield) actually evolved to be slightly further away from optimal than their ancestor. On the other hand, sub-optimal strains evolved to be closer. As Will very nicely put it, “FBA can either predict how you are or what you’ll become, but not both”.
2. We’ve been on a roll with Faculty of 1000! Lon and Miki’s PLoS One paper on FREQ-Seq to quantify allele frequencies cheaply and easily was kindly recommended by Andreas Wagner and Kathleen Sprouffske. Furthermore, our full FREQ-Seq kit is now available from Addgene.com, and they kindly wrote us up in their Summer Hot Articles newsletter.
3. I was very honored to have been nominated for a Star Family Prize for Excellence in Advising Harvard College undergraduates.
4. Finally, we have said goodbye and well wishes to Alex Betts, who visited us as an Erasmus Mundus visiting Master’s student (now on his way to a Ph.D. program at Oxford), and have welcomed Tim Scott, an visiting undergraduate student from University of Florida who joins us for the summer.
Less than two weeks after the last post, there is more happy news to report.
1. Nigel Delaney
‘s PLoS One paper
came out yesterday that describes the end result of an extended effort to push Methylobacterium
culturing as far as possible. It reports a new optimized medium, new strain lacking cellulose synthesis that caused clumping, and conditions and methods for high-throuput, robotic culturing that takes advantage of our earlier JALA paper
describing software to run automated lab systems.
3. Best of all, I am so thrilled to pass on that my PhD advisor, Mary Lidstrom
, was just elected yesterday
to the National Academy of Sciences. What a tremendously well-deserved selection for an incredible person. If nothing else, I have done well in choosing stupendous mentors: undergraduate work with Penny Chisholm
, PhD with Mary, and then postdoctoral work with Rich Lenski
. And now all three are in the NAS!
The last two weeks have seen much good news. First, Sean’s PLoS Genetics paper came out which describes analyses of global gene expression that occurred immediately after metabolic engineering of formaldehyde metabolism in Methylobacterium (i.e., acclimation to the new pathway) and after eight populations evolved to grow on methanol using a new pathway (i.e., adaptation). Remarkably, although there were massive transcriptional changes that were highly parallel across the evolved populations, nearly all of these simply reversed the immediate perturbations caused by swapping out the methanopterin pathway for a glutathione one. Second, in addition to the other kind press Miki’s Genetics paper on clonal interference that I mentioned before, undergraduate Lauren Claus wrote a very nice piece about it for the Harvard Crimson. Third, I am very thrilled to pass on that my graduate advisor, Mary Lidstrom (U. Washington), was named the laureate for the 2013 Procter & Gamble Award in Applied and Environmental Microbiology by ASM. Extremely well-earned! Fourth, I am extremely excited to say that our lab’s own Will Harcombe has had a successful job search, ending in an excruciating decision. He will be starting off 2014 as an Assistant Professor in the BioTechnology Institute at the University of Minnesota as a member of the Department of Ecology, Evolution and Behavior.
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.
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.
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.
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 News, GenomeWeb Daily News, Harvard Gazette, and University of Houston.