Evolution: Natural and Directed (MAS S61)

W 12:30-3pm in E15-341

Units: 3-0-6 (3-0-9 optional intensive option)

Catalog entry

Graduate subject in molecular evolution. Topics include mutation, recombination, evolvability, sexual reproduction and substitutes, experimental and directed evolution, genomic conflict, and gene drive. Classes will feature discussion-based critical analyses of the primary literature. At the end of the course, students will prepare short research proposals emphasizing research strategy, experimental design, presentation, and writing. 

For 12 units, students may undertake additional readings and write a full-length grant proposal or manuscript intended for publication.

K. Esvelt

No required or recommended textbooks. May be cross-listed under Course 7 in future iterations.

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. 


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.

Willem Stemmer (1994). Rapid evolution of a protein in vitro by DNA shuffling.

14 Feb     (no seminar)

21 Feb     How a landscape can be fit, and fitness dangerous

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.

Primary literature:

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

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

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


Gong and Bloom (2013). Stability-mediated epistasis constrains the evolution of an influenza protein.

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.

Peabody and Kao (2017). Sexual recombination and increased mutation rate expedite evolution of E. coli in varied fitness landscapes.

Vignuzzi and Andino (2006). Quasispecies diversity determines pathogenesis through cooperative interactions within a viral population.


Wang and Church (2009). Programming cells by multiplex genome engineering and accelerated evolution.

7 Mar      Running with the Red Queen

Primary literature:

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

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

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

14 Mar     Replaying the tape of life

Primary literature:

Weinreich and Hartl (2006). Darwinian evolution can follow only very few mutation paths to fitter proteins.

Blount and Lenski (2012). Genomic analysis of a key innovation in an experimental population of E. coli.

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


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

21 Mar     Why sex is great

Secondary literature:

Anderson and Phillips (2010). Outcrossing and the maintenance of males within C. elegans populations.

Primary literature:

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

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

Good and Desai (2014). Genetic diversity in the interference selection limit.


Good and Desai (2012). Distribution of fixed beneficial mutations and the rate of adaptation in asexual populations.

28 Mar     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.

4 Apr      CRISPR critters and controversial tricks

Primary literature:

Barrangou and Horvath (2007). CRISPR provides acquired resistance against viruses in prokaryotes.

Levin and Barrangou (2013). The population and evolutionary dynamics of phage and bacteria with CRISPR-mediated immunity.

Roth and Andersson (2004). Adaptive mutation: how growth under selection stimulates Lac+ reversion by increasing target copy number

Morreall and Doetsch (2015). Evidence for retromutagenesis as a mechanism for adaptive mutation in E. coli.

11 Apr     Antibiotic game theories

Primary literature:

Kirkup and Riley (2004). Antibiotic-mediated antagonism leads to a bacterial game of rock-paper-scissors in vivo.

Nahum and Kerr (2011). Evolution of restraint in a structured rock-paper-scissors community.

Yurtsev and Gore (2013). Bacterial cheating drives the population dynamics of cooperative antibiotic resistance plasmids.

18 Apr     Conflict is inevitable

Background reading:

Haig (1996). Gestational drive and the green-bearded placenta.

Primary literature:

Maynard and Karumanchi (2003). Excess placental sFlt1 may contribute to endothelial dysfunction hypertension and proteinuria in preeclampsia.

LePage and Bordenstein (2017). Prophage WO genes recapitulate and enhance Wolbachia-induced cytoplasmic incompatibility.


Stouthamer and Hurst (1999) Wolbachia pipientis: Microbial manipulator of arthropod reproduction.

Hoffmann and O'Neill (2011). Successful establishment of Wolbachia in Aedes populations to suppress dengue transmission.

25 Apr     Jumping genes

Background reading:

Fedoroff (2012). McClintock's challenge to the 21st century.

Haig (2016). Transposable elements: self-seekers of the germline, team players of the soma.

Litman and Fugmann (2010). The origins of vertebrate adaptive immunity.

Primary literature:

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

2 May      Driving genes

Primary literature:

Burt (2003). Site-specific selfish genes as tools for the control and genetic engineering of natural populations.

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.

9 May      Engineering: designing that which will eventually fail

Primary literature:

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

Noble, Min, and Esvelt (2017). Daisy drive systems for the alteration of local populations.

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

Rovner and Isaacs (2015). Recoded organisms engineered to depend on synthetic amino acids.

Optional reading:

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

16 May

Final presentations of research proposals.