Armita Nourmohammad

Lewis-Sigler Institute for Integrative Genomics, Princeton University

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

phenotype_stabilizingselection.pdf

ii. Adaptive evolution of molecular phenotypes

phenotype_adaptation.pdf

iii. Coevolution of phenotypes: antibody-viral interaction

main: coevolution.pdf SI: coevolution_si.pdf