In the morass of metagenomic sequence data on microbes, it is unclear what a unit should even be in a community. Ideally, one would want to uncover the core populations present: the set of strains that actually are exchanging genetic information and are reasonably cohesive, even in the presence of a degree of input from outside sources. The Polz lab has put forward a fantastic new method in Arevalo et al. “A reverse ecology approach based on a biological definition of microbial populations” (Cell, 2019. 178:820-834). for doing so that is based upon the simple concept that the length distribution of perfectly matching sequences can serve as a chronometer of separation. In the absence of exchange, two lineages emerging from the same genome sequence will ultimately accumulate random differences that will leave behind an exponential distribution of perfect sequence matches. If they continue to exchange, however, this will lead to an excess of longer sequence matches than expected. Indeed, this pattern is seen amongst strains previously identified as being of the same population. Furthermore, there is the substantial advantage that it identifies precisely which genes are being exchanged, thereby providing clues as to the success of one population versus each other, hence the concept of a “reverse” approach to ecology.
In our Preview – “Align to define: ecologically meaningful populations from genomes” (Cell, 2019. 178:767-768) – Sergey Stolyar, a Research Associate Professor working with my group, and I point out how these units defined upon exchange are actually narrower than “exact sequence variants” (ESVs), which have already been thought of as too narrow by some. We point out that the ecological distinctiveness of lineages in lab-based experimental evolution is often but one or a few mutations, so this seems quite consonant with their findings. It remains unclear whether these populations are equivalent to “species,” but this represents an exciting and refreshingly novel approach to letting genome sequences tell us what we should be paying attention to.
None of us are looking for extra work to do, but when invited to write a Perspective for this great paper out of the lab of Andreas Wagner, Jessica Lee (now at Global Viral) and I made time to make it happen. The Research Article from Zheng et al. – “Cryptic genetic variation accelerates evolution by opening access to diverse adaptive peaks” (Science, 2019. 365:347-353) – took advantage of the ability to select upon fluorescent proteins in a FACS machine to impose various selective pressures. They permitted cryptic variation to accumulate by imposing purifying selection upon yellow fluorescence for yfp variants. They then used this pool to begin selecting upon the upper range of green fluorescence. These diverse pools adapted faster and through a wider variety of paths than if they just began with the single ancestral yfp variant.
In our Perspective – “Tales from the cryp(ic)” (Science, 2019. 365:318-319) – we enjoyed pointing out comparisons to some awesome work of friends and colleagues that touched upon these questions: Jeremey Draghi‘s exploration of robustness, Eric Hayden‘s similar work with ribozymes, and Joe Thornton and Mike Harm‘s use of ancestral reconstruction to look at epistasis from a historical perspective.
What a wonderful surprise! I had no idea PNAS was doing a commentary on our paper, and then I found this excellent piece written by Jennifer Farrell and Sam Brown (Georgia Tech). They end their piece hoping that Will Harcombe (now at U. Minnesota) continued to evolve the two-species system described in this paper. Thankfully I know the answer is yes, and there will be more good stuff to come that he has carried forward in his own lab.
Eric Bruger and I penned a review (Bruger and Marx, 2018. Current Opinion in Microbiology) that seeks to address the manner in which sequencing technologies have opened the door to whole new questions in experimental evolution. It was a joy to highlight the incredible work our field has accomplished in such a short time. I knew sequencing would be coming when I started my lab in 2005, but the magnitude of change has been incredible.
In the past months we have had two papers on the E. coli–S. enterica system that Will Harcombe developed, and worked on when he was a postdoc in the lab.
One of these (Hynes et al., 2018. Biomedical Physics and Engineering Express) reports the ability to examine communities via bioprinting, and also represented a collaboration with two of my best friends Daniel Segrè and Nate Cady.
The second of these (Harcombe et al., 2018. PNAS) just came out a few weeks ago online in PNAS. It describes Will’s amazing finding of bidirectional costly mutualism evolving between species in the lab. Repeatedly E. coli evolved to break its own metabolism to excrete galactose to S. enterica during growth together on lactose (which S. enterica can’t use) in order to obtain methionine, which S. enterica had previously evolved to produce in return. I was excited to discover that, just a couple days ago, PNAS published a commentary on our paper penned by Jennifer Farrell and Sam Brown.
Back in 2013, I co-founded KnipBio with Larry Feinberg. KnipBio’s goal is to develop Methylobacterium as an aquaculture feed ingredient that can simultaneously reduce the need for fishmeal-derived protein and provide high-value components and properties. In the past two years, our first publications have come out describing the successful use of this single-cell protein with a variety of aquaculture species (Tlusty et al., 2017. PeerJ, Hardy et al., 2018. Aquaculture Research). It has been very exciting to see work move from the lab and translate to practical outcomes.
This past Tuesday, 11/13, Siavash Riazi presented his defense for a PhD in BCB entitled “Mathematical modeling and analysis of gene expression to understand phenotypic heterogeneity and the response of Methylobacterium extorquens to formaldehyde toxicity.” His work was co-advised by Chris Remien (Mathematics) and me, and represents his first PhD student, and my first to finish here at Idaho. Many thanks to committee members, Holly Wichman, Steve Krone, and Craig Miller. And most of all congrats to Dr. Riazi!