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To detect the genomic mechanisms underlying evolutionary dynamics of adaptation in sexually reproducing organisms, we analyze multigenerational whole genome sequences of  Drosophila melanogaster  adapting to extreme O 2  conditions over an experiment conducted for nearly two decades. We develop methods to analyze time-series genomics data and predict adaptive mechanisms. Here, we report a remarkable level of synchronicity in both hard and soft selective sweeps in replicate populations as well as the arrival of favorable de novo mutations that constitute a few asynchronized sweeps. We additionally make direct experimental observations of rare recombination events that combine multiple alleles on to a single, better-adapted haplotype. Based on the analyses of the genes in genomic intervals, we provide a deeper insight into the mechanisms of genome adaptation that allow complex organisms to survive harsh environments.

Multiple mechanisms drive genomic adaptation to extreme O2 levels in Drosophila melanogaster