No abstract

In most species daily rhythms are synchronized by the photoperiodic cycle. They are generated by the circadian system, which is made of a pacemaker, an entrainment pathway to this clock, and one or more output signals. In vertebrates, melatonin produced by the pineal organ is one of these outputs. The production of this time-keeping hormone is high at night and low during the day. Despite the fact that this is a well-preserved pattern, the pathways through which the photoperiodic information controls the rhythm have been profoundly modified from early vertebrates to mammals. The photoperiodic control is direct in fish and frogs and indirect in mammals. In the former, full circadian systems are found in photoreceptor cells of the pineal organ, retina, and possibly brain, thus forming a network where melatonin could be a hormonal synchronizer. In the latter, the three elements of a circadian system are scattered: the photoreceptive units are in the eyes, the clocks are in the suprachiasmatic nuclei of the hypothalamus, and the melatonin-producing units are in the pineal cells. Intermediate situations are observed in sauropsids. Differences are also seen at the level of the arylalkylamine N-acetyltransferase (AANAT), the enzyme responsible for the daily variations in melatonin production. In contrast to tetrapods, teleost fish AANATs are duplicated and display tissue-specific expression; also, pineal AANAT is special--it responds to temperature in a species-specific manner, which reflects the fish ecophysiological preferences. This review summarizes anatomical, structural, and molecular aspects of the evolution of the melatonin-producing system in vertebrates.

Melatonin (N-acetyl-5-methoxytrypamine) is the vertebrate hormone of the night: circulating levels at night are markedly higher than day levels. This increase is driven by precisely regulated increases in acetylation of serotonin in the pineal gland by arylalkylamine N-acetyltransferase (AANAT), the penultimate enzyme in the synthesis of melatonin. This unique essential role of AANAT in vertebrate timekeeping is recognized by the moniker the timezyme. AANAT is also found in the retina, where melatonin is thought to play a paracrine role. Here, we focused on the evolution of AANAT in early vertebrates. AANATs from Agnathans (lamprey) and Chondrichthyes (catshark and elephant shark) were cloned, and it was found that pineal glands and retinas from these groups express a form of AANAT that is compositionally, biochemically, and kinetically similar to AANATs found in bony vertebrates (VT-AANAT). Examination of the available genomes indicates that VT-AANAT is absent from other forms of life, including the Cephalochordate amphioxus. Phylogenetic analysis and evolutionary rate estimation indicate that VT-AANAT evolved from the nonvertebrate form of AANAT after the Cephalochordate-Vertebrate split over one-half billion years ago. The emergence of VT-AANAT apparently involved a dramatic acceleration of evolution that accompanied neofunctionalization after a duplication of the nonvertebrate AANAT gene. This scenario is consistent with the hypotheses that the advent of VT-AANAT contributed to the evolution of the pineal gland and lateral eyes from a common ancestral photodetector and that it was not a posthoc recruitment.E yes have evolved in all animals to facilitate interactions with the photic environment (1, 2). However, among animals, vertebrates are unique in that they also possess a photoneuroendocrine structure, the pineal gland (3). It converts the 24-h rhythm in environmental lighting into a 24-h rhythm in circulating melatonin, thereby providing a unique and valuable signal of the photic environment. The details of pineal evolution are not clear (4, 5). However, it has been posited that an essential element was arylalkylamine N-acetyltransferase (AANAT; E.C. 2.3.1.87), the penultimate enzyme in the melatonin biosynthesis pathway (6-8); this scenario is referred to as the AANAT hypothesis of pineal evolution (7,8).AANAT catalyzes the N-acetylation of arylalkylamines using acetyl CoA (AcCoA) as the acetyl group donor. The AANAT family, which belongs to the GCN5 superfamily (9, 10), is composed of two subfamilies termed vertebrate (VT) AANAT and nonvertebrate (NV) AANAT. † This nomenclature reflects the phylogenetic distribution of the family members (13-17). The most striking differences between VT-and NV-AANAT are found in regulatory and catalytic regions of the encoded proteins (Fig. 1), consistent with different metabolic roles (7,8).The NV-AANAT is thought to perform a detoxification function through acetylation of a broad range of endogenous and exogenous arylalkylamines and polyamines (13-16). It has been fo...