====== Evolution of molecular phenotypes: from gene regulation to immune system  ======

[[http://scholar.princeton.edu/armitan/home|Armita Nourmohammad]]

Lewis-Sigler Institute for Integrative Genomics, Princeton University

===== Summary =====

Molecular phenotypes, such as gene expression or protein binding affinities are important targets of natural selection, and are often subject to time-dependent pressure form the environment. However, the map between encoding DNA sequences and molecular phenotypes is often too difficult to quantify. In these lectures, I will show that universality is an emerging property of complex phenotypes, which are encoded by multiple genomic loci. I will introduce a non-equilibrium framework for adaptive dynamics of such phenotypes in time-dependent environments, and between co-evolving populations. In time-dependent environments, changes in the environment drive the evolution of the species, but not vice versa. As an example, I will present strong evidence that adaptation dominates the evolution of gene expression levels in Drosophila. Co-evolving populations reciprocally affect the fitness of each other, acting as time-dependent environments with feedback. As an example, I will show evidence of co-adaptation between interacting cellular populations of HIV viruses and the antibody repertoire of a patient over the course of an infection. In particular, I discuss the conditions for emergence of broadly neutralizing antibodies, which are recognized as critical for designing an effective vaccine against HIV.


**References:**

//i. Phenotype evolution under stabilizing selection//

{{:2017:courses:nourmohammad:phenotype_stabilizingselection.pdf|}}

//ii. Adaptive evolution of molecular phenotypes//

{{:2017:courses:nourmohammad:phenotype_adaptation.pdf|}}

//iii. Coevolution of phenotypes: antibody-viral interaction//

main: {{:2017:courses:nourmohammad:coevolution.pdf|}}
SI: {{:2017:courses:nourmohammad:coevolution_si.pdf|}}