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Since 1959, initially in conjunction with Dmitri Belyaev, Trut launched a program of experimental domestication of mammals. Trut and Belyaev showed that a few generations of selection for tameness led to a set of seemingly unrelated morphological and physiological traits. After Belyaev’s 1986 death, Trut studied diverse biological changes caused by selection for domestication. Recently this work has acquired a genomic dimension. For 33 years, Trut has led this program, which is generating widespread interest in domestication as a biological and experimental system. Her work has been crucial in showing the power of selection and diverse unanticipated consequences.