Fundamental issues related to the origin of melatonin and melatonin isomers during evolution: relation to their biological functions

Abstract

Melatonin and melatonin isomers exist and/or coexist in living organisms including yeasts, bacteria and plants. The levels of melatonin isomers are significantly higher than that of melatonin in some plants and in several fermented products such as in wine and bread. Currently, there are no reports documenting the presence of melatonin isomers in vertebrates. From an evolutionary point of view, it is unlikely that melatonin isomers do not exist in vertebrates. On the other hand, large quantities of the microbial flora exist in the gut of the vertebrates. These microorganisms frequently exchange materials with the host. Melatonin isomers, which are produced by these organisms inevitably enter the host's system. The origins of melatonin and its isomers can be traced back to photosynthetic bacteria and other primitive unicellular organisms. Since some of these bacteria are believed to be the precursors of mitochondria and chloroplasts these cellular organelles may be the primary sites of melatonin production in animals or in plants, respectively. Phylogenic analysis based on its rate-limiting synthetic enzyme, serotonin N-acetyltransferase (SNAT), indicates its multiple origins during evolution. Therefore, it is likely that melatonin and its isomer are also present in the domain of archaea, which perhaps require these molecules to protect them against hostile environments including extremely high or low temperature. Evidence indicates that the initial and primary function of melatonin and its isomers was to serve as the first-line of defence against oxidative stress and all other functions were acquired during evolution either by the process of adoption or by the extension of its antioxidative capacity.

Figure 1

Melatonin synthetic pathway in animals and in plants. Black identifies the animal pathway, green indicates the plant pathway and red is their common pathway. TPH: tryptophan hydroxylase; AADC: aromatic l-amino acid decarboxylase; An-SNAT; animal serotonin N-acetyltransferase (the vertebrate enzyme is known as aralkylamine N-acetyltransferase, AANAT); An-ASMT: animal N-acetylserotonin-O-methyltransferase; TDC: tryptophan decarboxylase; T5H: tryptamine 5-hydroxylase; Pl-SNAT: plant serotonin N-acetyltransferase; Pl-ASMT: plant N-acetylserotonin-O-methyltransferase.

Figure 2

Chemical structures of proposed melatonin isomers. The numbers identify the positions on the indole ring and the A or M represent the side chain A and side chain M, respectively. When A is located at position 3 and M at position 5, the molecule is melatonin.

Figure 3

Structural evolution of serotonin N-acetyltransferases (SNATs) among species (From Falcon et al. [12]). The major structural differences in SNATs among phylogenetically distant species are the regulatory regions; however, the catalytic cores of these enzymes share some similarity. The term vertebrates in Figure 3 refers more correctly to gnathostome vertebrates.

Figure 4

The phylogenetic tree of SNATs in different species. The homologous genes of SNATs in cyanobacteria, rice, Ovis aries and archaea were blasted in NCBI. The phylogenetic tree was constructed using the neighbor-joining method and a bootshrap test with 1000 iterations, using MEGA5.2 software. The scale represents the number of nucleotide changes during evolution. The GenBank accession numbers are NP_442603 (Cyanobacteria SNAT), AK059369 (Rice SNAT), NM_001009461.1 (Ovis aries SNAT), NP_579185.1 (Archaea PF1456 Pyrococcus furiosus DSM 3638 SNAT). The results indicated that the cyanobacterial SNAT gene is more closely related to that of rice.