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Tempo and mode in the endocannaboinoid system
John M McPartland1, Ryan W Norris, C William Kilpatrick
1GW Pharmaceuticals Ltd, Middlebury, VT 05753, USA. mcpruitt@verizon.net
Journal of Molecular Evolution
|August 7, 2007
Summary
The endocannabinoid system
Area of Science:
- Evolutionary biology
- Genomics
- Biochemistry
Background:
- The endocannabinoid system, comprising ligands like anandamide and 2-AG, interacts with numerous receptors and enzymes.
- Understanding the evolutionary pressures on these genes is crucial for deciphering their functional adaptations.
Purpose of the Study:
- To investigate the evolutionary tempo and selection pressures on genes within the endocannabinoid system.
- To identify specific genes that have undergone recent adaptive evolution.
Main Methods:
- Comparative genomics analysis of 18 endocannabinoid system genes across six species.
- Utilized bioinformatics platforms (LiKaKs, SNAP, FUGE) to assess evolutionary rates (RRE) and selection pressure (Ka/Ks).
- Employed extended haplotype homozygosity analysis on HapMap SNP data to detect recent positive selection.
Main Results:
- Endocannabinoid genes exhibited a significantly higher relative rate of evolution (RRE) in murids compared to primates.
- Human lineage-specific Ka/Ks calculations revealed significant variation across the 18 genes, with PTPN22 showing the highest ratio.
- Evidence of recent positive selection (selective sweep) was found in PTPN22, TRPV1, NAPE-PLD, and DAGLalpha genes.
Conclusions:
- The endocannabinoid system is generally under strong purifying selection, indicating functional constraint.
- Specific genes within the system show evidence of adaptive evolution, suggesting recent functional diversification.
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