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To maintain normal physiological functions, different tissues may have different developmental constraints on expressed genes. Consequently, the evolutionary tolerance for genomic evolution varies among tissues. Here, we formulate this argument as a “tissue-driven hypothesis” based on the stabilizing selection model. Moreover, several predicted genomic correlations are tested by the human–mouse microarray data. Our results are as follows. First, between the human and mouse, we have elaborated the among-tissue covariation between tissue expression distance (E_ti) and tissue sequence distance (D_ti). This highly significant E_ti − D_ti correlation emerges when the expression divergence and protein sequence divergence are under the same tissue constraints. Second, the tissue-driven hypothesis further explains the observed significant correlation between the tissue expression distance (between the human …