Category Archives: Humor

Optimizing the product of the wow factor and the beneficial mutation supply rate

This post follows up on my post from yesterday, which was about choosing a dilution factor in a microbial evolution experiment that avoids the loss of too many beneficial mutations during the transfer bottleneck.

If we only want to maximize the cumulative supply of beneficial mutations that survive dilution, then following the reasoning in yesterday’s post, we would choose the dilution factor (D) to maximize g Ne = (g2) Nmin = (g2) Nmax / (2g), where Nmax is a constant (the final population size) and D = 1 / (2g). Thus, we want to maximize (g2) / (2g) for g > 0, which gives g = ~2.885 and D = ~0.1354, which is in agreement with the result of Wahl et al. (2002, Genetics), as noted in a tweet by Danna Gifford.

The populations would therefore be diluted and regrow by ~7.4-fold each transfer cycle. But as discussed in my previous post, this approach does not account for the effects of clonal interference, diminishing-returns epistasis, and perhaps other important factors. And if I had maximized this quantity, the LTEE would only now be approaching a measly 29,000 generations!

So let’s not be purists about maximizing the supply of beneficial mutations that survive bottlenecks. There’s clearly also a “wow” factor associated with having lots and lots of generations.  This wow factor should naturally and powerfully reflect the increasing pleasure associated with more and more generations.  So let’s define wow = ge, which is both natural and powerful.  Therefore, we should maximize wow (g2) / (2g), which provides the perfect balance between the pleasure of having lots of generations and the pain of losing beneficial mutations during the transfer bottlenecks.

It turns out that the 100-fold dilution regime for the LTEE is almost perfect!  It gives a value for wow (g2) / (2g) of 75.93.  You can do a tiny bit better, though, with the optimal ~112-fold dilution regime, which gives a value of 76.03.

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What Was I Thinking?

The LTEE has run for over 10,000 days and almost 67,000 generations. It’s time to shut it down, as of today.

It’s been a hell of a lot of work, and we have almost nothing to show for it. As some astute commentators have noted around the web, the creatures in the flasks are still just bacteria—creatures, just as they were created.

If you read the first LTEE paper*, you’ll see we predicted the bacteria should become yeast by about 5,000 generations, nematodes at 15,000 generations or so, and fruit flies by 30,000 generations, maybe 35,000 at the outside.

After that, we’d have to stop the experiment anyhow, because we wouldn’t be able to freeze and bring them back alive any longer.

Plus, we’d have to get IRB approval for human experimentation if we ran it much past 50,000 generations.

Well, we’ve given the LTEE all this time, and still … they ’re just bacteria. I guess we’ve proven that Charles Darwin was wrong after all.

As an astute reviewer pointed out when we submitted that first paper, “I feel like a professor giving a poor grade to a good student.”  I should’ve listened and quit way back then. It would’ve saved everyone a lot of time and effort.

Now it’s going to be a hell of a lot of work next week emptying the freezers and autoclaving all those samples.

* Lenski, R. E., M. R. Rose, S. C. Simpson, and S. C. Tadler. 1991. Long-term experimental evolution in Escherichia coli. I. Adaptation and divergence during 2,000 generations. American Naturalist 138: 1315-1341.

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A Birthday Sonnet

This past weekend, I celebrated my 60th birthday with friends and family from all over. One of the roasters was Ben “The Bard” Kerr, a professor at the University of Washington and colleague in the BEACON Center for the Study of Evolution in Action.

Borrowing from another bard, Ben waxed poetic about one of the lineages in the long-term evolution experiment and raised a toast with this Shakespearean flask.

 

Ben Kerr's Skakespearean flask

ODE TO AN LTEE LINEAGE

Shall I compare Ara-3 to a summer’s day?

Thou start more humbly, but sure potentiate.

Rough spins do shake the darling bugs of Rich’s gaze,

And latecomer’s “fleece” hath all to port citrate.

One line’s long-shot passed by eleven lines,

And how was its controlled complex “skin” pinned?

Promoter capture, over some time refined.

By chance, with nature’s arranging force, trimmed.

But thy Cit-minus partner shall not fade

Nor gain possession of the flair of most

C4 shall Cit snag, now spawned by carbon trade

Then on it turns ‘til lines will species now boast

     So long these cells can achieve, so wise to see,

     So long lives this work- and awe is rife, Lenski.

 

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Another Birthday Haiku

As I said in my last post, I just celebrated my 60th birthday with lots of friends and family. Several folks produced new artistic works, including two lovely haikus that celebrate the E. coli long-term evolution experiment.

Here’s one from Mike Wiser, who did his doctoral research on the long-term lines. A highlight of his work was a paper showing that fitness trajectories in these populations tend to follow a power law, which has no upper bound, rather than an asymptotic rectangular, as I had previously assumed.

Living things adapt.
Evolution keeps going.
No peak yet in sight.

 

Power law prediction, 2013

[The power-law model (blue) predicts future fitness gains much more accurately than does the hyperbolic model (red).  Image modified from Wiser et al. (2013, Science 342: 1364-1367) and shown here under the doctrine of fair use.]

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Birthday Haiku

This past weekend I had my 60th birthday. I was delighted to celebrate it with wonderful colleagues, students, friends, and family.

At a dinner roast and toast, everyone sang When We’re Sixty Four (Thousand), a tribute from the E. coli in the LTEE to the People of the Lab. And several friends came up with new contributions at the intersection of science and culture.

This beauty is from Andy Ellington, a professor in the Center for Systems and Synthetic Biology at the University of Texas and a member of the BEACON Center. As background, Andy coauthored a recent paper that helps to elucidate how one LTEE population evolved the novel ability to use citrate.

Without further ado, here’s his haiku …

Citrate just beyond.

Acetate potentiates.

Glucose is all gone.

 

Citrate

[Image of citrate molecule from Wikimedia Commons]

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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?

 

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Bacterial Niche Finally Defined

The following scholarly contribution comes from my wife Madeleine Lenski after conversing with her “sister” (my former postdoc) Valeria Souza.

For those with an itch for criteria,

Scratch this: What’s a niche for bacteria?

Don’t take me to task

If I answer “a flask” –

It’s a bitch from warm broth to Siberia.

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January 19, 2016 · 9:08 pm