Function, structure, evolution, regulation of a potent drug target, arylalkylamine N-acetyltransferase

Zhang, Lei; Tang, Yu; Merkler, David J.; Han, Qian

doi:10.1016/bs.apcsb.2022.11.002

Cited by 2 publications

(1 citation statement)

References 60 publications

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“…AANAT is highly conserved in vertebrates, and it may have evolved early on through horizontal gene transfer [44] and thereafter was driven by natural selection [24]. The genetic diversity of the NE and CE lineages with longer hibernation times was greater than that of the SW lineage, indicating evolutionary potential and the ability to adapt to environmental changes [45].…”

Section: Discussionmentioning

confidence: 99%

Adaptive Evolution of the Greater Horseshoe Bat AANAT: Insights into the Link between AANAT and Hibernation Rhythms

Zhao,

Wang,

Liu

et al. 2024

Animals

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Arylalkylamine N-acetyltransferase (AANAT) is a crucial rate-limiting enzyme in the synthesis of melatonin. AANAT has been confirmed to be independently duplicated and inactivated in different animal taxa in order to adapt to the environment. However, the evolutionary forces associated with having a single copy of AANAT remain unclear. The greater horseshoe bat has a single copy of AANAT but exhibits different hibernation rhythms in various populations. We analyzed the adaptive evolution at the gene and protein levels of AANAT from three distinct genetic lineages in China: northeast (NE), central east (CE), and southwest (SW). The results revealed greater genetic diversity in the AANAT loci of the NE and CE lineage populations that have longer hibernation times, and there were two positive selection loci. The catalytic capacity of AANAT in the Liaoning population that underwent positive selection was significantly higher than that of the Yunnan population (p < 0.05). This difference may be related to the lower proportion of α helix and the variation in two interface residues. The adaptive evolution of AANAT was significantly correlated with climate and environment (p < 0.05). After controlling for geographical factors (latitude and altitude), the evolution of AANAT by the negative temperature factor was represented by the monthly mean temperature (r = −0.6, p < 0.05). The results identified the gene level variation, functional adaptation, and evolutionary driving factors of AANAT, provide an important foundation for further understanding the adaptive evolution of the single copy of AANAT in pteropods, and may offer evidence for adaptive hibernation rhythms in bats.

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Section: Discussionmentioning

confidence: 99%

Adaptive Evolution of the Greater Horseshoe Bat AANAT: Insights into the Link between AANAT and Hibernation Rhythms

Zhao,

Wang,

Liu

et al. 2024

Animals

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Role of arylalkylamine N‐acetyltransferase 7 in reproduction and limb pigmentation of Aedes aegypti

Tang,

Jiang,

Huang

et al. 2024

Insect Molecular Biology

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Arylalkylamine N‐acetyltransferase (aaNAT) is a crucial enzyme that catalyses the transfer of acetyl groups from acetyl coenzyme A to arylalkylamines and arylamines. Evolutionary studies have identified a distinct class of aaNATs specific to mosquitoes, yet their functions remain elusive. This study focuses on Ae‐aaNAT7, a mosquito‐unique gene in Aedes aegypti (Diptera:Culicidae), to explore its functionality. Temporal and spatial expression analysis of Ae‐aaNAT7 mRNA revealed high expression during embryonic development and in first‐instar larvae, with notable expression in the limbs of adult mosquitoes based on tissue expression profiling. By further employing CRISPR/Cas9 technology for loss‐of‐function studies, our investigation revealed a reduction in the area of white spotting in the limbs of Ae‐aaNAT7 mutant adult mosquitoes. Further investigation revealed a significant decrease in the fecundity and hatchability of the mutants. Dissection of the ovaries from Ae‐aaNAT7 heterozygous mutants showed a noticeable reduction in the oocyte area compared with wild type. Dissection of the exochorion of the eggs from Ae‐aaNAT7 homozygous mutants consistently revealed a striking absence of mature embryos. In addition, RNA interference experiments targeting Ae‐aaNAT7 in males resulted in a reduction in fecundity, but no effect on hatchability was observed. These collective insights underscore the substantial impact of Ae‐aaNAT7 on reproduction and its pivotal contribution to adult limb pigmentation in Ae. aegypti. These revelations offer insights pivotal for the strategic design of future insecticide targets.

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Function, structure, evolution, regulation of a potent drug target, arylalkylamine N-acetyltransferase

Cited by 2 publications

References 60 publications

Adaptive Evolution of the Greater Horseshoe Bat AANAT: Insights into the Link between AANAT and Hibernation Rhythms

Adaptive Evolution of the Greater Horseshoe Bat AANAT: Insights into the Link between AANAT and Hibernation Rhythms

Role of arylalkylamine N‐acetyltransferase 7 in reproduction and limb pigmentation of Aedes aegypti

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