AbstractAs the largest European herbivore, the wisent (Bison bonasus) is emblematic of the continent wildlife but has unclear origins. Here, we infer its demographic and adaptive histories from two individual whole genome sequences via a detailed comparative analysis with bovine genomes. We estimate that the wisent and bovine species diverged from 1.7×106to 850,000 YBP through a speciation process involving an extended period of limited gene flow. Our data further support the occurrence of more recent secondary contacts, posterior to theBos taurusandBos indicusdivergence (ca. 150,000 YBP), between the wisent and (European) taurine cattle lineages. Although the wisent and bovine population sizes experienced a similar sharp decline since the Last Glacial Maximum, we find that the wisent demography remained more fluctuating during the Pleistocene. This is in agreement with a scenario in which wisents responded to successive glaciations by habitat fragmentation rather than southward and eastward migration as for the bovine ancestors.We finally detect 423 genes under positive selection between the wisent and bovine lineages, which shed a new light on the genome response to different living conditions (temperature, available food resource and pathogen exposure) and on the key gene functions altered by the domestication process.