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.

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!

Happy birthday, Charles and Abe

Charles Darwin was born into wealth and privilege in England 210 years ago, while across the ocean on the same day Abraham Lincoln was born to a poor family in Kentucky.

Besides the coincidence of their birthdays, there are other interesting connections. Lincoln is known, of course, for preserving the Union and freeing slaves through the Emancipation Proclamation. But Lincoln also signed the law that established the National Academy of Sciences, which provides pro bono scientific advice to the federal government. And while Darwin is known for his work on evolution, he was also a prominent overseas voice in the abolitionist movement. During the voyage of HMS Beagle, Darwin had a heated argument with the captain, Robert FitzRoy, who defended the institution of slavery.

Darwin was onboard the ship as a gentleman naturalist, but the voyage was far from easy. Planned as a 2-year expedition, it was almost 5 years before 27-year-old Darwin returned to England in 1836. He was frequently seasick and, back home, often ill. Nevertheless, his observations, specimens, and notes laid the groundwork for his thinking that culminated with On the Origin of Species in 1859. That book presented Darwin’s evidence for descent with modification (what we now call evolution), and it put forward a mechanism—natural selection—that explains how species acquire traits that fit them to their environments.

Many of us first encounter the idea of evolution as children, when we see pictures or fossils of dinosaurs and other long-ago creatures. But evolution isn’t confined to the past; it continues to occur all around us. Some ongoing evolution causes problems for our health and wellbeing, such as pathogenic microbes evolving resistance to antibiotics. In many cases, though, evolution is used to solve problems in agriculture, biotechnology, and engineering. For example, Frances Arnold won a 2018 Nobel Prize in Chemistry for her work using evolution to generate valuable enzymes with improved and even new functions.

In my lab, we study evolution in action using bacteria, taking advantage of their rapid generations. We can freeze and later revive living cells, allowing us to compare organisms from different generations—in essence, time travel! In an ongoing experiment I started in 1988, we’ve watched 12 populations of E. coli evolve for over 70,000 generations. We can quantify the Darwinian process of adaptation by natural selection, and we’ve sequenced the bacteria’s genomes to understand the coupling between adaptation and genotypic evolution. We’ve even seen the emergence of a new metabolic function that transcends the usual definition of E. coli as a species.

It’s amazing just how much evolution has taken place during a few decades in these small flasks. It leaves me with awe at what evolution has achieved over the last four billion years on our planet … and with wonder about what more will unfold in the fullness of time.

This post was written for the National Academy of Sciences Facebook page, where it also appears.

When We’re Sixty Four (Thousand)

From the E. coli in the LTEE to the People of the Lab

[To be sung along to this Beatles classic]

 

When we get older, losing our fimbriae,

Many years from now,

Will you still be sending us our thiamine,

Birthday greetings, Erlenmeyer wine?

If we were mutants, crazy and fit,

Would that make you snore?

Will you still feed us, will you still freeze us,

When we’re sixty-four?

 

You’ll be older too,

And if you say the word,

We’ll evolve with you.

 

We could be handy, helping your pubs,

When your grants are gone.

You can write a paper by the fireside,

Weekend days give no time to hide.

Colonies growing, dotting the plates,

Who could ask for more?

Will you still feed us, will you still freeze us,

When we’re sixty-four?

 

Every summer you can buy a freezer when the space gets tight,

If it’s not too dear.

Save our clonal mix,

Plus and minus progeny,

Ara One to Six.

 

Keeping the notebook, pipetting each drop,

Track trajectories.

Indicate precisely what you think will change.

Hypothesize, test, unlimited range.

Give us your data, sequence and store,

Evolving evermore.

Will you still feed us, will you still freeze us,

When we’re sixty-four?

 

Thirty Years

No, the LTEE did not suddenly jump forward by almost 3 years. That milestone will be reached on February 24, 2018.

Next Friday is the end of the semester at MSU and, for me, it will mark 30 years that I’ve been on the faculty: six at UC-Irvine, and 24 here at MSU. (I also taught for one semester at Dartmouth as a sabbatical replacement, while I was doing a postdoc at UMass.)

Holy cow: 30 years. Where did all that time go?

Well, a lot of it was spent advising, supervising, and mentoring graduate students. And those have been some of the most interesting, enjoyable, and rewarding professional experiences that I can imagine.

In fact, this afternoon Caroline Turner defended her dissertation – congratulations Dr. Turner! Her dissertation is titled “Experimental evolution and ecological consequences: new niches and changing stoichiometry.” It contains four fascinating and meaty chapters, two on the interplay between evolutionary and ecological processes in the LTEE population that evolved the ability to grow on citrate, and two on evolved changes in the elemental stoichiometry of bacterial cells over experimental time scales.

Caroline is the 20th student to complete her Ph.D. with me serving as the advisor or co-advisor. Here they all are, with links to their professional pages or related sites.

1. Felisa Smith, Ph.D. in 1991 from UC-Irvine.
2. John Mittler, Ph.D. in 1992 from UC-Irvine.
3. Mike Travisano, Ph.D. in 1993 from MSU.
4. Paul Turner, Ph.D. in 1995 from MSU.
5. Greg Velicer, Ph.D. in 1997 from MSU.
6. Brendan Bohannan, Ph.D. in 1997 from MSU.
7. Phil Gerrish, Ph.D. in 1998 from MSU.
8. Farida Vasi, Ph.D. in 2000 from MSU.
9. Vaughn Cooper, Ph.D. in 2000 from MSU.
10. Danny Rozen, Ph.D. in 2000 from MSU.
11. Kristina Hillesland, Ph.D. in 2004 from MSU.
12. Elizabeth Ostrowski, Ph.D. in 2005 from MSU.
13. Bob Woods, Ph.D. in 2005 from MSU.
14. Dule Misevic, Ph.D. in 2006 from MSU.
15. Gabe Yedid, Ph.D. in 2007 from MSU.
16. Sean Sleight, Ph.D. in 2007 from MSU.
17. Zack Blount, Ph.D. in 2011 from MSU.
18. Justin Meyer, Ph.D. in 2012 from MSU.
19. Luis Zaman, Ph.D. in 2014 from MSU. (Charles Ofria was the primary advisor.)
20. Caroline Turner, Ph.D. in 2015 from MSU.

There are also 8 doctoral students at various stages currently in my group at MSU including Brian Wade (Ph.D. candidate), Mike Wiser (Ph.D. candidate), Rohan Maddamsetti (Ph.D. candidate), Alita Burmeister (Ph.D. candidate), Elizabeth Baird, Jay Bundy, Nkrumah Grant, and Kyle Card.

My own advisor – the late, great Nelson Hairston, Sr. – said that he expected his graduate students to shed sweat and maybe even occasional tears, but not blood. I would imagine the same has been true for my students.

Thirty years, holy cow. Time flies when you’re working hard and having fun!

Added November 4, 2015:  And now #21 in my 31st year, as  Mike Wiser successfully defended his dissertation today!

Window Dressing

The window to the lab has been updated, courtesy of Zack Blount.