ESI MIRA Project Summary – Seth Rudman Project Summary A comprehensive mechanistic understanding of the process of adaptation that is predictive of outcomes is a fundamental goal in evolutionary biology and advances towards this goal have profound implications for human health. Adaptation, particularly in animal populations, is primarily studied retrospectively through the patterns it produces. Yet, decades of research have demonstrated that adaptation in natural populations occurs quickly. A growing number of field experiments, including much of my recent work, have demonstrated key insight into the process of adaptation by observing as it occurs. With advances in sequencing and bioinformatics it is now tractable to use forward-in-time experimental approaches to directly observe the process of adaptation in sexually reproducing diploid animals by studying repeated changes across independent populations, which is amongst the strongest evidence of adaptation. Combining a forward-in-time experimental approach with manipulations of aspects of genetic diversity, the selective landscape, or demography can directly test hypotheses about the genomic architecture, constraint, and pace of adaptation providing key insight into the process of rapid adaptation. I propose experiments united by an approach that leverages existing molecular and population genetics tools in Drosophila melanogaster for replicated field experiments that directly test key hypotheses about the relationship between genetic variation, adaptation, and the predictability of evolution in animal populations. The primary questions are: 1) Are genotype-phenotype relationships of complex traits predictive of the outcomes of adaptation; 2) Are large effect loci essential for rapid adaptation from standing genetic variation; 3) What is the relationship between the amount of genetic diversity and the pace and parallelism of adaptation; and 4) Does gene flow into locally adapted but declining populations promote or constrain adaptation and population persistence and does this depend on the amount of genetic diversity in the recipient population. In addition to directly answering these questions, these experiments will provide data on the pace, predictability, and importance of adaptation in shaping both genomic diversity and the persistence of populations inhabiting rapidly changing environments. The work I propose here is part of building a research program that tests fundamental questions in evolutionary biology by manipulating factors hypothesized to influence adaptation and directly observing their effects with the ultimate aim of building a mechanistic understanding of adaptation.