蛋白質通常與其他蛋白質進行複雜的相互作用,並且功能相關的蛋白質通常表現出類似的進化路徑[65][69]。 一個可能的解釋是共同適應[65]。 線粒體 DNA 和核 DNA 編碼的蛋白質之間的相互作用就是一個例子。線粒體 DNA 比核 DNA 具有更高的演化/突變率,特別是在特定編碼區域[68][69]。 然而,為了維持生理功能,選擇功能上會相互作用的蛋白質,亦即選擇共同適應的核 DNA 是更為有利的[68]。
線粒體 DNA 和核 DNA 序列之間的協同適應已在橈足類生物 Tigriopus californicus 中進行了研究[68] 。 該物種同種族群中 COII 編碼序列的線粒體 DNA 差異很大[68]。 當一個群體的線粒體 DNA 置於另一個群體的核背景中時,細胞色素c氧化酶活性顯著降低,表明存在共同適應。 結果顯示線粒體 DNA 的變異與環境因素之間不太可能存在關係。 更可能的解釋是線粒體 DNA 的中性演化,以及由線粒體 DNA 的中性演化驅動的核 DNA 的補償性變化(孤立群體中隨時間推移的隨機突變)[68]。
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