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In Other News

Today is the 34th birthday of the LTEE, which I started on February 24, 1988. 

With the invasion of Ukraine, however, it’s not a day to celebrate.

 The LTEE will move to the capable lab and hands of Jeff Barrick this Spring, after all 12 lines have reached 75,000 generations.

Over the decades, several lines fell behind others due to cross-contamination (or concerns about the possibility), which we detected by examining the alternating Arabinose marker and seeing the resulting colony colors on TA plates. Those lines were then restarted from whole-population samples, but they would be 500 generations behind the others (or a multiple of 500 generations behind in some cases).

The picture above shows red and white colonies growing on TA agar in a Petri dish. The red colonies cannot grow on the sugar arabinose that is part of the TA medium, while the white ones can use arabinose. Half of the LTEE lines started from red colonies (Ara–1 to Ara–6), and half started from white colonies (Ara+1 to Ara+6). We alternate the red and white lines each day during their propagation. That way, if cross-contamination occurs, we can detect it by the presence of bacteria that make colonies that are the wrong color. We check colonies before every periodic freeze of the LTEE. These days, with DNA sequencing, we can also use derived mutations that are unique to each lineage to check whether a putative contamination event is real or not. (Indeed, in some populations, especially those that evolved hypermutability, the colony markers don’t work like they did when the LTEE started.) If we confirm that a cross-contamination event has occurred, we restart the affected population from the last frozen sample of that population.

So today, Devin Lake will propagate the last two lagging populations. Our lab will continue to propagate them until they, too, reach 75,000 generations. The last one should reach that goal in late May.

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New Beginnings

Greetings on this winter solstice!  The winter solstice marks a sort of new beginning, as the days become longer for the next half year, before then becoming shorter until the cycle is repeated. 

Every day, the E. coli populations in the long-term evolution experiment (LTEE) experience a cycle of renewed resources and growth followed by depletion of their food and then waiting for the next transfer event. 

On a much longer timescale, the LTEE also experiences cycles as it is passed from one scientific generation to the next. With that in mind, we’ve made a new website that reflects the beginning of the second scientific generation of the LTEE, as the populations and responsibility for their sustenance will soon pass from my lab to that of the new director, Jeff Barrick.

On this website, you can get an introduction and quick overview of the LTEE including how it works, its goals, some of the key findings, and plans for its future.  You can see a timeline of the experiment with some of the milestones and key events in its history.  You can read, watch, and listen to a few of the news stories about the LTEE.  You can find resources including protocols and links to important datasets.  You can search and find links to the publications that report findings from the LTEE itself as well as descendant experiments that have used the LTEE lines. And last, but not least, you can see the talented people who’ve done and are doing the work behind the LTEE, including propagating the populations, performing analyses, analyzing data, and reporting the findings.

We’ve probably missed some papers, and we know that we’re still missing photos for some participants. We’ve also only scratched the surface of reporting past news.  So please let one of us know if you find someone or something LTEE-related that you’d like to see included on this website.  For now, enjoy the new beginnings as seasons and generations continue onward!

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Vinyl

Who remembers the old LP record albums?  They were made of vinyl, and music was recorded by etching tiny variations along a spiral groove. You put an LP onto a turntable, and you set the stylus with a fine needle into the groove. As the turntable rotated, the needle vibrated according to those tiny variations along the groove. And by amplifying that analog signal, music emanated from your speakers.    

The LP replaced an earlier format that used shellac instead of vinyl. The older format rotated on the turntable at 78 rpm, and a 12-inch diameter record allowed for only about 5 minutes of music per side. The vinyl LP allowed finer etching along a narrower groove, and these albums turned at 33 and 1/3 rpm. This technology allowed over 20 minutes of music to be recorded on each side of the disc. Hence the acronym LP, which stands for “long play.”

Why am I telling you this? I started the LTEE on February 24, 1988. A year on our planet is about 365.25 days, and so a century is 36,525 days. There have been 12,175 days from February 24, 1988, until today. That’s exactly one third of a century.

The LTEE has now revolved around our sun 33 and 1/3 times!  I think that qualifies as an LP.

An old LP album cover …
even older than the LTEE
.

Writing in the lab notebook on the occasion of the LTEE circling the sun 33 and 1/3 times.

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How NOT to Write a Response to Reviewers

Last year I outlined my strategy for writing a response to reviewers.  It was intended primarily for early-career scientists, and the strategy I outlined was most relevant for a paper that had generally positive reviews.

One piece of my advice was to try to view every comment as constructive, even if you disagree with it. Reviewers are often mistaken on some points; indeed, one of the major benefits of the review process is that it calls attention to where we, as authors, have not explained ourselves clearly to the reader.

In my experience as an author and editor, it is pretty rare for a reviewer to say things that are truly hostile or otherwise inappropriate. However, it does occasionally happen that reviewers are unfair. 

I’ve blogged previously about one particularly aggressive and unconstructive review that my coauthors and I received. It was a harsh critique of the very first paper on the long-term evolution experiment with E. coli.  Fortunately, the other reviewer was very positive, and the editor requested a revision.

For some time I’ve thought about posting my response to that negative review. However, I thought the response was perhaps somewhat ill-tempered and overly long. Now, more than 30 years later, if I were advising a young scientist facing a similar review, I’d probably say: “Forget revising it for that journal. Just move on and try again elsewhere.”  But I didn’t do that myself, and I guess it worked out alright in the end.

Without further ado, here’s the response to that reviewer. (You can click on the image for each of the 4 pages to enlarge it.)


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Celebrating Black in STEM

I have been very fortunate to know and work with outstanding Black scientists throughout my career.  Here are a few of them.

I met Joe Graves when we were undergraduates at Oberlin College.  We took an evolution course together.  I remember discussing with Joe our mutual fascination with evolution and wondering how we might go about studying it.  I met up again with Joe at UC-Irvine, where we were both conducting evolution experiments—Joe using fruit flies, and me with bacteria.  Joe and I reconnected once more when he and I became founding members of the BEACON Center for the Study of Evolution in Action.  Joe now studies bacterial evolution, and we are becoming scientific collaborators as well.

JoAnn White was an ecologist at UNC, studying the life-history and population dynamics of periodical cicadas.  She served on my doctoral advisory committee and was a highly successful faculty member.  Unfortunately, she left academia, even though she had tenure, because it was too frustrating. I was honored that she asked me to write a reference letter when she moved to a new profession.  But it was a terrible loss for academia to lose such an outstanding scientist and role model as JoAnn White.

Paul Turner was one of my first graduate students.  He joined my lab in the Department of Ecology and Evolution at UC-Irvine, and he moved with me to MSU, receiving his Ph.D. in 1995.  Paul has impressed me in many ways, not only as a superb scientist and mentor, but also in his upbeat outlook on life.  Somehow he manages to smile and laugh about the challenges of being a departmental chair and interim dean, even while running a lab that conducts ground-breaking research.

Lynette Ekunwe was my lab manager and technician for seven years after I moved to MSU. She helped to sustain the long-term evolution experiment with E. coli after its move from UC-Irvine, and she helped run my lab group as it grew in size. Lynette moved to Jackson State University when her husband, the late Steve Ekunwe, took a faculty position there. After the move, Lynette earned a doctorate in public health, and she now works in the field of epidemiology.

I first met Scott Edwards when he was a graduate student at UC-Berkeley. I suspected that he was a rising star, and I was right.  Although Scott and I have not collaborated on actual science, we’ve worked together in other ways.  Scott and I served successive terms as Presidents of the Society for the Study of Evolution, and he has been a valued member of the External Advisory Board for the BEACON Center.

Shenandoah Oden was an undergraduate from Detroit when she joined my lab in the 1990s.  She worked with postdoc Santiago Elena on measuring the fitness effects of random insertion mutations in E. coli, leading to a paper in Genetica. What I remember best about Shenandoah is a question she asked me right after Brendan Bohannan presented his dissertation seminar: “How do scientists come up with the questions they ask?” I told her that was the best question that any student had ever asked me.  It reminded me of how Joe Graves and I, when we were undergrads, wondered how we might study evolution. To Shenandoah, I explained the importance of personal curiosity and mentors in finding questions that are both interesting and answerable.

Marwa AdewaMaia Rowles and Kiyana Weatherspoon were three excellent undergraduate researchers in my lab, all of whom were mentored by Zachary Blount. Maia and Kiyana were coauthors on a paper in the Proceedings of the Royal Society, London B, which reported the results of what we call the “all-hands project”—one in which a generation of lab members performed a set of parallel assays to measure the subtle changes in fitness in late generations of the long-term evolution experiment with E. coli. Marwa now works in the field of veterinary medical research, while Maia and Kiyana are pursuing careers with a biomedical focus.

Judi Brown Clarke was, until very recently, the Diversity Director for our BEACON Center. In that role she generated and managed many successful programs that introduced hundreds of students at all levels to evolution and provided them with opportunities to engage in scientific research. She also was a great listener and valuable source of advice for many of us when we faced personal challenges and setbacks. An Olympic medalist, Judi recently became the Chief Diversity Officer at Stony Brook University.

I met Jay Bundy in 2013, at the Evolution meeting in Snowbird, Utah.  Who was this student who was asking so many thoughtful, insightful questions of the speakers?  I ran into Jay as we rushed between talks, introduced myself, and learned that he was a masters student at Penn State.  He wasn’t sure if he was interested in microbes, but I encouraged him to think about joining BEACON.  Jay came to MSU, first as a BEACON staff member contributing to education and outreach activities, and then as a graduate student in the Department of Integrative Biology.  He also contributed to the all-hands project.  However, he switched from studying bacteria to digital organisms, and he’s now performing and analyzing experiments to quantify how the duration of history in an evolving lineage’s previous environment influences its subsequent evolution in a new environment. Stay tuned for Jay’s findings—he’s working on a huge paper. Jay is as deeply thoughtful about science and life as I imagined when I first heard his questions at the Evolution meeting.

I also met Nkrumah Grant in 2013, when he visited MSU while exploring possible graduate programs.  He immediately impressed me with his personal story of overcoming obstacles.  Nkrumah explained to me his love of science as a child, and how he had gotten discouraged and derailed before undertaking a concerted effort to pursue his dream of science and scholarship.  And pursue it he did … and continues to do.  From a G.E.D. to a Ph.D.  Co-author on the all-hands project, co-first-author on a paper just published in eLife, and three more papers posted to bioRxiv in the last few weeks.  He also just defended his dissertation, giving a beautiful public seminar followed by an engaging, collegial exam.  Nkrumah has done all this and more while being a dedicated father and working tirelessly to promote equity and inclusion in science.

Last but not least, Ali Abdel Magid and Jalin Jordan are two of the current generation of superb undergraduate researchers in the lab. Ali is working with Nkrumah on the evolution of bacterial cell size, while Jalin works with Kyle Card on the evolution of antibiotic resistance.  Both Ali and Jalin are also working toward future careers in medicine. This summer, they are reading work that integrates evolution and medicine including the landmark book, Why We Get Sick, by Nesse and Williams, and the path-breaking paper by Tami Lieberman et al. on the evolution of bacteria in the lungs of CF patients.

My science is better, and my life richer, because of all these people, and many more.  How much better science would be, and how much richer all of our lives would be, if we would open more doors, listen more carefully, and live, learn, and work together.

***

After reading a draft of this essay, Nkrumah Grant, Joe Graves, and Jay Bundy all asked me to say more about this:  How can we achieve the aspirations expressed in my closing sentence above? 

I plan to reflect more on their vital question.  In the meantime, I invite readers who have ideas to put them in the comments below.

EDIT: I should also acknowledge two other influences: A high-school teacher, Mrs. Clayton, who taught a Black History class that I took, and who introduced me to Frederick Douglass, whose autobiography I read with awe and admiration.

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Five More Years

The E. coli long-term evolution experiment (LTEE) began in 1988, and it has run for over 32 years with only occasional interruptions. The latest interruption, of course, reflects the temporary closure of my lab during the ongoing coronavirus pandemic. Fortunately, one of the advantages of working with bacteria is that we can freeze population samples and later revive them, which will allow us to resume their daily propagation when it is prudent to do so.  Indeed, we’ve frozen samples of all 12 populations throughout the LTEE’s history, allowing “time travel” to measure and analyze their fitness trajectories, genome evolution, historical contingencies, and more.

Even as the experiment is on ice, the lab team continues to analyze recently collected data, prepare papers that report their findings, and make plans for future work. Their analyses use data collected from the LTEE itself, as well as from various experiments spun off from the LTEE.  Nkrumah Grant is writing up analyses of genomic and phenotypic aspects of metabolic evolution in the LTEE populations.  Kyle Card is examining genome sequences for evidence of historical contingencies that influence the evolution of antibiotic resistance. Zachary Blount is comparing the evolution of new populations propagated in citrate-only versus citrate + glucose media. Minako Izutsu is examining the effects of population size on the genetic targets of selection, while Devin Lake is performing numerical simulations to understand the effects of population size on the dynamics of adaptive evolution.  So everyone remains busy and engaged in science, even with the lab temporarily closed.

Today, I’m excited to announce two new developments.  First, the National Science Foundation (NSF) has renewed the grant that supports the LTEE for the next 5 years. This grant enables the continued propagation of the LTEE lines, the storage of frozen samples, and some core analyses of the evolving populations. The grant is funded through the NSF’s Long Term Research in Environmental Biology (LTREB) Program, which “supports the generation of extended time series of data to address important questions in evolutionary biology, ecology, and ecosystem science.” Thank you to the reviewers and program officers for their endorsement of our research, and to the American public and policy-makers for supporting the NSF’s mission “to promote the progress of science.”

Second, Jeff Barrick joins me as co-PI on this grant for the next 5 years, and I expect he will be the lead PI after that period.  In fact, Jeff and his team will take over the daily propagation of the LTEE populations and storage of the sample collection even before then. I’m not planning to retire during the coming grant period. Instead, this transfer of responsibility is intended to ensure that the LTEE remains in good hands for decades to come. In the meantime, Jeff’s group will conduct some analyses of the LTEE lines even before they take over the daily responsibilities, while my team will continue working on the lines after the handoff occurs.

Several years ago I wrote about the qualifications of scientists who would lead the LTEE into the future: “My thinking is that each successive scientist responsible for the LTEE would, ideally, be young enough that he or she could direct the project for 25 years or so, but senior enough to have been promoted and tenured based on his or her independent achievements in a relevant field (evolutionary biology, genomics, microbiology, etc.). Thus, the LTEE would continue in parallel with that person’s other research, rather than requiring his or her full effort, just like my team has conducted other research in addition to the LTEE.”

Jeff is an outstanding young scientist with all of these attributes. Two years ago he was promoted to Associate Professor with tenure in the Department of Molecular Biosciences at the University of Texas at Austin.  He has expertise in multiple areas relevant to the LTEE including evolution, microbiology, genomics, bioinformatics, biochemistry, molecular biology, and synthetic biology. He directs a substantial team of technicians, postdocs, and graduate students, which will provide ample coverage for the daily LTEE transfers (including weekends and holidays). Last but not least, Jeff has participated in the LTEE and made many contributions to it including:

  • Participated in propagating the LTEE lines and related activities while he was a postdoc in my lab from 2006 to 2010.
  • Authored many papers using samples from the LTEE, including almost all of them that have analyzed genome sequences as well as several recent papers examining the genetic underpinnings of the ability to use citrate that evolved in one lineage.
  • Developed the open-source breseq computational pipeline for comprehensively identifying mutations that distinguish ancestral and evolved genomes.

Someone might reasonably ask if the LTEE will work in the same way when it is moved to another site. The answer is yes: the environment is simple and defined, so it is readily reproduced. Indeed, I moved the LTEE from UC-Irvine to MSU many years ago, the lab has moved between buildings here at MSU, and we’ve shared strains with scientists at many other institutions, where measurements and inferences have been satisfactorily reproducible. As an additional check, Jeff’s team at UT-Austin ran a set of the competition assays that we use to measure the relative fitness of evolved and ancestral bacteria, and we compared the new data to data that we had previously obtained here at MSU. The two datasets agreed well, in line with the inherent measurement noise in assessing relative fitness. Fitness is the most integrative measure of performance of the LTEE populations, and it is potentially sensitive to subtle differences in conditions. These results provide further evidence that, when the time comes, the LTEE can continue its journey of adaptation and innovation in its new home.

Evolve, LTEE, evolve!

LTEE flasks repeating

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We Interrupt this Nasty Virus with Some Good News about Bacteria

Today is the 32nd birthday of the E. coli long-term evolution experiment (LTEE).  I started it on February 24th, 1988, when I was at the University of Califonia, Irvine.

Notebook entry start of LTEEIt also happens to be daily transfer number 11,000 for the experiment.  But wait, you ask: Is 365 x 32 really equal to 11,000?  (Not to mention the complication of leap years.)

LTEE flasks repeating

No!  365 x 32 = 11,680.  We’re almost 2 years behind perfection!  Over the years, we missed daily transfers for various reasons including the fact the experiment was frozen for several months around the time of my move from Irvine to Michigan State University, as well as some missed transfers and various mishaps (including contamination) along the way that have led us to restart the experiment from frozen samples.

Luckily, we don’t have to go back to the beginning–the LTEE wouldn’t have survived if we did. We freeze whole-population samples every 75 days, and those provide the backups that keep us going when needed.

So the LTEE is 32 years old today.  The evolving bacteria lineages, though, are younger, at a little over 30 years (11,000 / 365).  I prefer to think of them as timeless, though … having survived in and adapted to their tiny flask worlds for more than 73,000 generations.

Here’s grad student and lab manager Devin Lake doing today’s transfer.

Devin LTEE 32 years

And here’s Devin & me with the lab notebook. Devin is pointing to today’s entries.

Devin and Rich with LTEE notebook for 32nd birthday

And here’s what we wrote:

LTEE notebook 32nd birthday

For those with pathogens on their mind (and that’s a lot of us, with the new coronavirus spreading), you might wonder: Aren’t E. coli dangerous?  The short answer is only rarely. All of us have harmless or even beneficial strains of E. coli and many other bacterial species in our GI tract. The LTEE uses one of these harmless strains, one that has been studied in many labs for close to a century without problems. There are some strains of E. coli, though, that are nasty, and which are usually acquired by eating contaminated foods.  So wash your raw fruits and vegetables, cook your meats, and don’t worry about the LTEE bacteria … Just wish them a happy birthday today, and many more years of scientific discovery.

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