The mitochondria is essential for cell physiology, having a direct impact in organismal fitness. Because mitochondrial function requires a close interaction with nuclear encoded proteins, the fast evolving mitochondrial genes are likely to elicit coevolution at nucelar genes. Hybridization can disrupt such coadaptation, resulting in mito-nuclear incompatibilities and hybrid breakdown at early stages of population divergence. In the copepod Tigriopus californicus, extreme rates of mitochondrial evolution have resulted in hybrid breakdown between multiple populations. Yet, it is unclear how many genomic regions are involved in mito-nuclear incompatibilities, and whether those genes are the same in independently evolving populations. To answer these questions, we generate replicated hybrid swarms characterized by similar nuclear composition but alternative mitochondrial backgrounds, and evolve these populations over 11 generations. Life history traits showed consistent fitness recovery to, or above, parental level, suggesting Darwinian evolution against mito-nuclear incompatibilities in both mitochondrial backgrounds. Whole genome re-sequencing has shown consistent allelic frequency changes across replicates evolving under the same mitochondrial background, identifying genomic regions likely affected by incompatibilities. Although some of these genomic regions are the same in alternative mitochondrial backgrounds, other regions only change in one background. Together, these results show that although mito-nuclear incompatibilities have a relatively simple genetic architecture, they are often asymmetric, as predicted by theoretical work.