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    Replaying the tape of life

14 Mar     When fitness is dangerous

21 Mar     Cooperators and cheaters stick together

28 Mar    (spring break)

04 Apr    Antibiotic game theories

11 Apr     Why sex is great

18 Apr     CRISPR conflict is inevitable

25 Apr     Jumping genes

02 May   Driving genes

09 May   Engineering: to design that which will eventually fail

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)











2018 Syllabus    (Remainder of 2019 syllabus under revision)


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. 


Optional:

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.


Optional:

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.


Optional:

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.


Optional:

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.


Optional:

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.