A Comparative Genomics Study on the Molecular Evolution of Serotonin/Melatonin Biosynthesizing Enzymes in Vertebrates

Abstract

Serotonin is important in vertebrates for its crucial roles in regulation of various physiological functions. Investigations on how the biosynthesizing enzymes mediate serotonin production and conversion during biological processes have been active in the past decades. However, a clear-cut picture of these enzymes in molecular evolution is very limited, particularly when the complexity is imaginable in fishes since teleosts had experienced additional whole genome duplication (WGD) event(s) than tetrapods. Since serotonin is the main intermediate product during melatonin biosynthesis from tryptophan, we therefore summarize an overview of recent discoveries about molecular evolution of the four melatonin biosynthesizing enzymes, especially the L-aromatic amino acid decarboxylase (AAAD) for serotonin production and aralkylamine N-acetyltransferase (AANAT) for serotonin conversion in vertebrates. Novel copies of these genes, possibly due to WGD, were discovered in fishes. Detailed sequence comparisons revealed various variant sites in these newly identified genes, suggesting functional changes from the conventional recognition of these enzymes. These interesting advances will benefit readers to obtain new insights into related genomic differences between mammals and fishes, with an emphasis on the potential specificity for AANAT in naturally cave-restricted and deep-sea fishes.

Evolutionary Genomics Reveals Multiple Functions of Arylalkylamine N-Acetyltransferase in Fish

“…Interestingly, Sa has sometimes lost its external eyeballs and lens, and its body has become somehow transparent or with albinism. Although abnormality of aanat genes has not been determined in these species, we identified a similar premature stop in the encoding region of aaad gene as we found in the cave-restricted Mexican tetra ( Lv et al, 2020 ), implying a possibility of weakening or disappearing rhythms in cavefishes, possibly caused by low melatonin levels ( Yang et al, 2016 ).…”

“…Atlantic cod and Mexican tetra, for instance, have lost aanat1a and aanat1b , respectively ( Li et al, 2015 ). The loss of aanat2 has not been identified in any fish genomes so far ( Lv et al, 2020 ), suggesting a highly conserved function of this isotype ( Zilberman-Peled et al, 2011 ).…”

“…Presumably, CNVs of aanat in fish are a combined result of gene duplication and WGD followed by gene loss ( Falcón et al, 2014 ), while some fish or groups have their own preferences on which aanat duplicate is to be retained and which one is to be lost. In ray-fins, aanat2 seems to be essential and is retained in all genomes sequenced so far ( Table 1 ), although it may be inactivated due to frameshift mutations in certain species like deep-sea snailfish ( Lv et al, 2020 ; Mu et al, 2021 ). Amphibious giant-fin mudskipper has lost aanat1a ( You et al, 2014 ), whereas Ostariophysi group has lost aanat1b ( Li et al, 2015 ).…”

“…Meanwhile, the genome of its closed relative Tanaka’s snailfish ( Liparis tanakae , TS) from shallow sea was also available in the same article. We performed a detailed comparison of aanat2 gene structures between MHS and TS ( Lv et al, 2020 ), and observed a frameshift insertion in MHS, while its relative TS was normal. As we supposed, the insertion may lead to an inactivity of AANAT2, and hence consequent low levels of blood melatonin in MHS ( Lv et al, 2020 ).…”

Whole genome sequencing of a snailfish from the Yap Trench (~7,000 m) clarifies the molecular mechanisms underlying adaptation to the deep sea

“…The λmax of YHS rhodopsin is 479–484 nm, which is lower than the levels found in shallow-water teleosts ( Fig 5C ). Moreover, the same frameshift insertion in aralkylamine N-acetyltransferase 2 ( aanat2 ), the critical gene for melatonin biosynthesis, was observed in both YHS ( S9 Fig ) and Mariana hadal snailfish [ 31 ], which led to the inactivation of AANAT2. This inactivation in the two hadal snailfishes may result in low levels of blood melatonin, which potentially reflects an adaptation to the darkness in hadal environments.…”