UC San Diego

Genetic adaptation is central to shaping phenotype diversity among populations. If there was not any genetic adaptation, Homo sapiens was not able to migrate out of their original habitat, east of Africa, to colonize the planet. Interestingly, adaptation has enabled us to occupy a wider range of adverse environments such as, arctic, high-altitude, and highly pathogenic (e.g. areas with high rates of transmission of Malaria) regions. Other phenotypes such as skin pigmentation, size of stature, lactose intolerance and several disease susceptibility are directly linked to genetic adaptation.

Adaptation also play an important role in global burden of disease and mortality. One every three deaths worldwide is attributed to the evolution of large asexual cell populations. Adaptation provide pathogens to ability to persist to the immune system or exogenous drug to avoid recovery of the host. It also enables them to revive and relapse the disease after obtaining the drug resistance allele, that is the case for Cancer, HIV, Malaria and many other lethal disease. Moreover, some of the ethnic populations also have a significantly lower susceptibility to an specific disease, such as pulmonary hypertension, Malaria, cardiovascular disease, etc.

In all the cases, better understanding of mechanisms of adaptation and the genomic targets of the selection can provide actionable information. For instance, the tedious and expensive process of drug discovery can be facilitated by taking into account of disease susceptibility targets. Better therapy drugs can be made by targeting the adapted loci on the pathogen. Finally, mapping the targets of adaptation provides insights into cryptic biological processes.

While human biology is the center of attention, model organisms provide convenient, inexpensive, and salable (to populations) framework to test evolutionary hypotheses. This owes to the fact that the molecular mechanisms of evolution are predominantly similar between any living organism.

Here in this dissertation, I utilize experimental evolution of \dmel to test multiple evolutionary hypotheses regarding the mechanisms, targets, modes and tempo of adaptation. To answer these questions, I develop genomic time-series models to describe data and find targets of selection. Using the evolutionary models I analyzed an ethnic population to find disease susceptibility genes.