Overfishing not only drastically reduces the number of fish in an exploited population but is often selective for body size removing the largest individuals from a population. Here, we study experimentally the evolutionary effects of size-selective harvesting using whole genome sequencing on a model organism; the zebrafish, which also allows us to quantify gene ontology terms due to the high-resolution reference genome. We demonstrate genomic shifts in the populations exposed to size-selective harvesting for five generations and show reduced genetic diversity in all harvested lines, including control line (non-size-selected). We also determine differences in gene ontogeny, with enrichment in nervous system related genes. Our results illuminate the biological processes underlying fisheries-induced genetic changes, hence contribute towards the understanding of the changes potentially associated with the vulnerability of an exploited population to future stressors.