Heart rate (HR) is a reflection of cardiac function as well as of the lifespan and energy metabolism among mammals. In comparison with most terrestrial mammals, the extraordinary reduction of cetacean HR rarely has been explored. It has been shown that the decreased HR contributes to an increase of lifespan, and high efficiency of energy utilization which provides many advantages for cetacean adaptation into aquatic habitats. However, the molecular mechanisms leading to the reduced HR in cetaceans remains unresolved until now. Branch models and branch-site models combined with analysis of protein functional differentiation, based on the maximum likelihood method have been used in the present research to test the molecular evolution acting on cetacean exchange proteins directly activated by cAMP (Epac1 and Epac2), two vital molecules in the cAMP signal that controls HR. Our results show an accelerated evolution of Epac1 at the combined branch of Baleen whales and sperm whale (Physeter macrocephalus). Branch-site models have determined remarkable positive selection at the ancestor node of baleen whales with positively selected sites located in the protein catalytic domain. Furthermore, functional modification of Epac1 also has been detected in cetaceans.  In addition, strong positive selection of Epac2 in the bowhead whale (Balaena mysticetus) with a lifespan of up to 200 years has been discovered as was seen for Epac1. These results suggest adaptive evolution of Epac1 and Epac2 in cetaceans, which might not only result in reduced HR, but also may contribute to extended lifespans and high effective energy utilization.

心率即心脏跳动的速度，不仅反映了心脏的功能,还与寿命的长短及能量代谢有关。与大多数陆生哺乳动物相比，鲸类心率显著降低。降低的心率有助于鲸类寿命的延长及能量的高效利用，便于其适应极端的海洋环境，而这一适应的分子机制尚不清楚。鉴于此，本研究采用基于最大似然法的枝模型、枝位点模型结合蛋白质功能差异分析等方法，对控制心率的环状腺苷酸结合蛋白（Epac1 和Epac2）基因进行适应性探究。分析结果表明，Epac1在长寿鲸类即须鲸类和抹香鲸（Physeter macrocephalus）组合进化支中检测到加速进化过程，且枝位点模型在须鲸类祖先支中检测到的强烈的正选择位点均位于功能重要的催化区；另外，该蛋白质在鲸类中还发生了显著的功能修饰（θ=0.5296 ± 0.1300；P<0.001）。对Epac2进行相同的分析发现，该基因在寿命长达200年之久的弓头鲸（Balaena mysticetus）中检测到的正选择位点同样位于功能重要的催化区。上述结果提示Epac1和Epac2在鲸类中均产生了适应性进化，这一方面可能有助于鲸类心率降低，另一方面也可能与其较长的寿命及高效的能量利用有关。