Happy 27th birthday to the LTEE!

The title says it all:  today is the 27^th birthday of the long-term evolution experiment (LTEE) with E. coli.

Well, the title doesn’t really say everything. I also want to give thanks to the many people—not to mention the trillions of bacteria—who have made it possible for the LTEE to keep on going and giving.

So thank you to all of the students, postdocs, and colleagues with whom I’ve collaborated on this project. There are too many to list here, but you will find their names on the papers that have come from the LTEE. I’ll call out just two, on this occasion, for special thanks. Dom Schneider has been an amazingly talented and generous collaborator for so many years—in fact, our first co-authored paper on the LTEE dates back to 1999. And Neerja Hajela has worked with me for 20 years now, and she is the most organized, dedicated, and all-around wonderful technician and lab manager that one could ever have.

Special thanks, too, to Madeleine Lenski, who has tolerated my long-term affair with the LTEE, and who wisely advised me to keep it going on one or two occasions when I was looking in other directions.

[The image below shows the abstract from the first paper on the LTEE, which appeared in The American Naturalist in 1991. It is reproduced here under the doctrine of fair use.  Some of the conclusions have changed a bit as the LTEE has had more time and we’ve gathered more data—that’s science!]

Questions from Jeremy Fox about the LTEE, part 2

EDIT (23 June 2015): PLOS Biology has published a condensed version of this blog-conversation.

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This is part 2, I guess, of my response to Jeremy Fox from his questions about the LTEE over at the Dynamic Ecology blog.

It’s not an answer to his 2^nd question, but it’s a partial answer to the first part of his 3^rd question. (Have I got you confused already? Me, too.) Well anyhow, Jeremy asked:

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• Did the LTEE have any hypotheses initially, and if so, how were you going to test them? This question probably just reflects laziness on my part, not having gone back and read the first publications arising from the LTEE, sorry. 🙂 I ask because, with just one treatment and no quantitative a priori model of how the experiment should turn out, it’s not clear to me how it initially could’ve been framed as a hypothesis test. For instance, I don’t see how to frame it as a test of any hypothesis about the interplay of chance and determinism in evolution. It’s hard to imagine getting any result besides some mixture of the two, and there’s no “control” or a priori theoretical expectation to compare that mixture to. Am I being dense here? (in addition to being lazy…)

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Short answer: Yes, the LTEE had many hypotheses, some pretty clear and explicit, some less so. (What, did you think I was swimming completely naked?)

Medium answer that will be fleshed out in later responses: Before we get to specific hypotheses—those formal, testable suppositions and predictions—I like to begin with general questions about how and why things are they way they are. So, what were the questions the LTEE originally set out to answer? (I emphasize “originally” because new or substantially refined questions have arisen over the course of the project, as we’ve answered some questions, made new observations, framed new questions, etc.)

What follows below are three overarching sets of questions that I hoped, long ago, the LTEE could answer, at least in the context of the simple flask-world that it encompassed. I present all three sets of questions  in some of my talks about the LTEE. However, in my talks to broad public audiences – like my Darwin Day talk at the University of Calgary next week – I focus especially on the third set of questions – about the repeatability of evolution – because I think it is the most interesting to people who are not necessarily evolutionary biologists or even scientists, but who are curious about the world in which we live.

A few more thoughts: The first set of questions, about the dynamics of adaptation, include ones where I had clear  expectations that were testable in a fairly standard hypothesis-driven framework. For example, I was pretty sure we would see the rate of fitness improvement decelerate over time (and it has), and I was also pretty sure we’d see a quasi-step-like dynamic to the early fitness increases (and we did). Nonetheless, these analyses have yielded surprises as well, including evidence (and my new strong conviction) that fitness can increase indefinitely, and essentially without limit, even in a constant environment. In regards to the second set of questions, about the dynamics of genome evolution and their coupling to phenotypic changes–I’m sure these were part of my original thinking, but I will readily admit that I had almost no idea how I would answer them. Hope sprung eternal, I guess; fortunately, wonderful collaborators—like the molecular microbiologist Dom Schneider—and brand new technologies—wow, sequencing entire genomes—saved the LTEE.

 

An Absence of Posts, an Abundance of Talks, and More

Dear Reader:  No, I have not given up on this blog.  But I’ve been busy, busy, busy!

In the last four weeks alone, I have traveled to the University of Arizona, Harvard University, Duquesne University, and Princeton University.  Besides giving talks at each place (two public lectures and two academic seminars, with cumulative audiences of well over a thousand people), I have met with dozens and dozens of amazing scientists, from graduate students and postdocs to faculty both young and old.  It’s been a blast:  an exhausting blast, but a blast all the same!

And next week?  I’m hosting four terrific colleagues from two continents who will work with me to begin making sense of hundreds of newly sequenced genomes from the LTEE.

Oh, and we have some more job searches starting next week.

And did I mention?  We just had a fascinating (if I may so myself) and complex paper come out today in Science (on-line express for now) on the most deeply divergent (i.e., oldest sustained polymorphism) of the 12 LTEE populations.  And no, it’s not about the citrate eaters from population Ara–3.

Plucain, J., T. Hindré, M. Le Gac, O. Tenaillon, S. Cruveiller, C. Médigue, N. Leiby, W. R. Harcombe, C. J. Marx, R. E. Lenski, D. Schneider.  2014.  Epistasis and allele specificity in the emergence of a stable polymorphism in Escherichia coli.  Science.

It’s population Ara–2 instead, where two lineages—dubbed the Larges (L) and Smalls (S)—have coexisted for several tens of thousands of generations.  In superb research led by Dr. Jessica Plucain that she did in the lab of my long-time collaborator (and dear friend!) Prof. Dom Schneider (Grenoble, France), Jessica led the work to identify—out of hundreds of mutations—three that are sufficient to allow a “constructed” S ecotype (i.e., the ancestor plus three derived alleles) to invade and stably coexist with the evolved L ecotype.  Ecological context and specific genetic interactions are key to establishing this “half” of the polymorphism … and the other “half” of the story— what makes the L ecotype special—might well turn out to be just as complex, or perhaps even more so.

The S and L types are especially challenging (even painful!) to work with because this population became a mutator very early on—before the two lineages diverged—and so there are many, many mutations to contend with; moreover, they make colonies on agar plates that are quite challenging to score and count.  So congratulations to Jessica, Dom, and other members of Dom’s lab for their perseverance in studying this extremely interesting population.

Also on the list of authors are Prof. Chris Marx and two members of his lab.  They performed metabolic analyses showing how the carbon fluxes through the central metabolism of the S ecotype have diverged from both the ancestor and the L ecotype.  Chris was a postdoc in my lab almost a decade ago, but most of his work (then and since) has been on experimental evolution using Methylobacterium, and so this is the first paper we’ve co-authored.

There was a production error, though, in the on-line version of our paper; the final sentence of the abstract was dropped (except for one word).  The abstract, in total, should read as follows:

“Ecological opportunities promote population divergence into coexisting lineages. However, the genetic mechanisms that enable new lineages to exploit these opportunities are poorly understood except in cases of single mutations. We examined how two Escherichia coli lineages diverged from their common ancestor at the outset of a long-term coexistence. By sequencing genomes and reconstructing the genetic history of one lineage, we showed that three mutations together were sufficient to produce the frequency-dependent fitness effects that allowed this lineage to invade and stably coexist with the other. These mutations all affected regulatory genes and collectively caused substantial metabolic changes. Moreover, the particular derived alleles were critical for the initial divergence and invasion, indicating that the establishment of this polymorphism depended on specific epistatic interactions.”

[Edited on 07-Mar-2014:  The on-line PDF at Science Express now has the complete abstract.]

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The picture below shows Dom Schneider and Richard Lenski in Paris in 2013.  They are holding a petri dish that Jessica Plucain made to celebrate the 25th birthday of the LTEE.