Evolution: Natural and Directed (MAS.841)

Th 1:00-2:30pm in E15-466

Units: 3-0-9

Evolution is cleverer than we are. Even though it knows nothing about its subject – or indeed anything – “the blind watchmaker” solves problems in ways that we would never have imagined. It has shaped everything alive, and most of the interesting phenomena that are not. Our cultures, beliefs, institutions, and identities are all governed by evolution, for what are they but collections of imperfectly replicating patterns of information?

Harness evolution effectively, and we can accomplish feats far beyond the capabilities of rational design. But evolved systems don’t just start off as black boxes – they’re written in spaghetti code. As a rule, there are many more interactions between evolved components than for human-designed systems, which prioritize simplicity and modularity. That makes evolved systems more difficult to engineer, but potentially easier to further evolve.

Moreover, evolution can’t think ahead. It doesn’t know when it’s going down a blind alley, because it doesn’t know anything. And it's slippery: it can perfectly solve problems of our selection, but unbeknownst to us, those may not be the problems we meant to specify. You get what you select for, which is not necessarily what you want. There are obvious parallels between the directed evolution of biomolecules and machine learning, and the lessons of one system are often highly relevant to working with the other.

In this reading-intensive course, we will seek to understand evolution at its most comprehensible by examining its effects on molecules encoded by nucleic acids. We’ll read and discuss select recent and classical papers on biological evolution, including computational simulations thereof, as well as attempts to direct evolution and prevent it from breaking our designs. We’ll look at game theory and gene drives, sex and mutation, evolvability and design. Meetings will be analogous to journal club sessions, with focused deep dives into the primary literature and discussions of implications for science, engineering, and even philosophy. A semester-long project will focus on something relevant to evolution yet productive outside of the course, be it a grant proposal for submission or a manuscript for publication.

Interested students with a primary focus in fields other than biology are encouraged to attend.


07 Feb     Molecular sex for fun and profit

14 Feb     How a landscape can be fit

21 Feb     Running with the Red Queen

28 Feb     When diversity is strength - and weakness

07 Mar    Better Than Nature 1: Ecology and Energy

14 Mar    Better Than Nature 2: Evolutionary Hazards

21 Mar    Engineering: To design that which will eventually fail

28 Mar    (spring break)

04 Apr    Driving genes

11 Apr     Why sex is great

18 Apr     Cooperators and cheaters stick together

25 Apr     Jumping genes

02 May   tbd

09 May   tbd

16 May   Group selections and wild ideas

23 May   Presentations



Catalog entry

Units: 3-0-9

Graduate subject in molecular evolution. Topics include mutation, recombination, evolvability, sexual reproduction and substitutes, experimental and directed evolution, genomic conflict, and gene drive. Meetings will feature discussion-based critical analyses of the primary literature. Students will write either a short grant proposal or a manuscript intended for publication.

K. Esvelt

No required or recommended textbooks. Check with graduate program administrators concerning elective credit.


Why a graduate-level course on molecular evolution at MIT?

Graduate-level courses should be interesting and relevant. Evolution is arguably the most interesting explanatory phenomenon that exists, so that should take care of itself. Reading the primary literature on the current state of the art, identifying flaws, and clearly summarizing for others is a vital skill for just about everyone interested in science and technology. As such, the course is intended to be an exploration of how evolution works as glimpsed through the literature. 

Why evolution?

Because just about everything humans care about is composed of informational patterns, understanding the ways they evolve and change - primarily through the simplified case of biological nucleic acids - has broad implications for biological and cultural evolution, morality, and the future of society. 

2019 Syllabus    


7 Feb      Molecular sex for fun and profit

Background reading:

Arnold (1999). Unnatural selection: molecular sex for fun and profit.

Primary literature:

Bartel and Szostak (1993). Isolation of new ribozymes from a large pool of random sequences.


14 Feb      How a landscape can be fit

Historical primary literature:

Wright (1932). The roles of mutation, inbreeding, crossbreeding, and selection in evolution.

Background review:

Romero and Arnold (2009). Exploring protein fitness landscapes by directed evolution.

Pigliucci (2006). High-dimensional fitness landscapes and speciation. (book chapter 3, PDF)


Primary literature:

Kashtan and Alon (2007). Varying environments can speed up evolution.


21 Feb        Running with the Red Queen

Primary literature:

Mills and Spiegelman (1967). An extracellular Darwinian experiment with a self-duplicating nucleic acid molecule. (PDF)

Wright and Joyce (1997). Continuous in vitro evolution of catalytic function. (PDF)

Esvelt and Liu (2011). A system for the continuous directed evolution of biomolecules. (PDF)


28 Feb     Diversity is strength (and weakness)

Primary literature:

Doulatov and Miller (2004). Tropism switching in Bordetella bacteriophage defines a family of diversity-generating retroelements. (PDF)

Ravikumar and Liu (2018). Scalable, continuous evolution of genes at mutation rates above genomic error thresholds. (PDF)

Wilke and Adami (2001). Evolution of digital organisms at high mutation rates leads to survival of the flattest. (PDF)


7 Mar      Better Than Nature 1: Ecology and Energy

Background reading:

Steiner and Fitzsimmons (2017). Rescue of American chestnut with extraspecific genes following its destruction by a naturalized pathogen. (PDF)

Primary literature:

Newhouse and Powell (2014). Transgenic American chestnuts show enhanced blight resistance and transmit the trait to T1 progeny. (PDF)

South and Ort (2019). Synthetic glycolate metabolism pathways stimulate crop growth and productivity in the field. (PDF)

Recommended book:

DarwinianAgriculture


14 Mar      Better Than Nature 2: Evolutionary Hazards

Primary literature:

Imai and Kawaoka (2012). Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets.

Meyer, Dobias, Weitz, Barrick, Quick, and Lenski (2012). Repeatability and contingency in the evolution of a key innovation in phage lambda.

Lajoie and Isaacs (2013). Genomically recoded organisms expand biological functions.

Optional:

Dickinson and Liu (2013). Experimental interrogation of the path dependence and stochasticity of protein evolution using phage-assisted continuous evolution.


21 Mar      Engineering: to design that which will eventually fail

Primary literature:

Tanner and Kierkegaard (2014). Dominant drug targets suppress the emergence of antiviral resistance.

Mandell and Church (2015). Biocontainment of genetically modified organisms by synthetic protein design.

Agmon and Boeke (2017). Low escape-rate genome safeguards with minimal molecular perturbation of Saccharomyces cerevisiae.


4 Apr      Driving Genes

Historical literature:

Curtis (1968). Possible use of translocations to fix desirable genes in pest populations. (PDF)

Primary literature:

Akbari and Hay (2013). A synthetic gene drive system for local, reversible modification and suppression of insect populations.

Esvelt, Smidler, Catteruccia, Church (2014). RNA-guided gene drives for the alteration of wild populations.

Optional:

Noble, Min, and Esvelt (2016). Daisy drive systems for the alteration of local populations.

Recommended book:

Burt and Trivers (2008) Genes in Conflict.


11 Apr Why sex is great

Historical primary literature:

Maynard Smith, J. (1971). What use is sex? J. Theor. Biol. 30, 319. (PDF)

Primary literature:

Colegrave, N. (2002). Sex releases the speed limit on evolution. (PDF)

Gladyshev and Meselson (2008). Extreme resistance of bdelloid rotifers to ionizing radiation.

Becks and Agrawal (2012). The evolution of sex is favoured during adaptation to new environments.


18 Apr Jumping genes and enablement

Longo and Kauffman (2012). No entailing laws, but enablement, in the evolution of the biosphere. (PDF)


Lynch and Wagner (2011). Transposon-mediated rewiring of gene regulatory networks contributed to the evolution of pregnancy.

Ivancevic and Adelson (2019). Horizontal transfer of BovB and L1 retrotransposons in eukaryotes.


25 Apr Cooperators and cheaters stick together

Primary literature:

Ratcliff and Travisano (2015). Origins of multicellular evolvability in snowflake yeast.

Koschwanez and Murray (2013). Improved use of a public good selects for the evolution of undifferentiated multicellularity.

Diard and Hardt (2013). Stabilization of cooperative virulence by the expression of an avirulent phenotype.

Waite and Shou (2012). Adaptation to a new environment allows cooperators to purge cheaters stochastically.


2 May Entropy, chemical space, and evolution (guest lecture: Jeremy England)

Literature: TBD