Abstract
Hypocretin system is composed of hypocretins (hcrts) and their receptors (hcrtrs), which has multiple vital functions. Hypocretins work via hypocretin receptors and it is reported that functional differentiation occurred in hcrtrs. It is necessary to figure out the evolution process of hypocretin receptors. In our study, we adopt a comprehensive approach and various bioinformatics tools to analyse the evolution process of HCRTR gene family. It turns out that the second round of whole genome duplication in early vertebrate ancestry and the independent round in fish ancestry may contribute to the diversity of HCRTR gene family. HCRTR1 of fishes and mammals are not the same receptor, which means that there are three members in the family. HCRTR2 is proved to be the most ancient one in HCRTR gene family. After duplication events, the structure of HCRTR1 diverged from HCRTR2 owing to relaxed selective pressure. Negative selection is the predominant evolutionary force acting on the HCRTR gene family but HCRTR1 of mammals is found to be subjected to positive selection. Our study gains insight into the molecular evolution process of HCRTR gene family, which contributes to the further study of the system.
Highlights
IntroductionHypocretin system is composed of hypocretins (hcrts) and their receptors (hcrtrs)
Hypocretin system is composed of hypocretins and their receptors
It was universally believed that HCRTR1 was specific to mammals while HCRTR2 existed in all the vertebrates
Summary
Hypocretin system is composed of hypocretins (hcrts) and their receptors (hcrtrs). There are two hypocretins, hcrta and hcrtb. Both of them are derived by proteolytic processing from a common precursor preproorexin coded by HCRT [1]. There are two types of receptors found in vertebrates, named hcrtr and hcrtr. Hcrtr has similar affinity for both hypocretins, whereas hcrtr favors hcrta [2]. Studies on knockout or neuron-depleted animal models indicate hypocretin system is important in maintaining normal vital signs such as basal blood pressure [14], respiratory rate [15], and energy expenditure [16,17,18]
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