K Kannabium BioDev · Evolutionary biology
ENPT-BR
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Chordata · Molecular evolution · Comparative genomics

Gene ancestry and duplication
in the origin of CB1 and CB2 receptors.

Compare BfCBR and CiCBR records with the inferred duplication preceding vertebrate CB1 and CB2. Sequence evidence alone cannot establish receptor function.

Examine phylogenetic relationships ↘ Synthetic topology · branch lengths not to scale

01 · Interpretive principle

The tree represents evolutionary relationships among living lineages

The positions of Cephalochordata, Tunicata, and Vertebrata indicate shared ancestry and patterns of divergence. Every terminal branch represents an extant lineage; direct ancestry requires separate historical and phylogenetic evidence.

Conceptual illustration of a marine environment with a lancelet, tunicates, and a transmembrane protein
Comparative contextChordate lineages document independent evolutionary trajectories.

02 · Phylogenetic synthesis

Distribution of co-orthologs and origin of vertebrate paralogs

The tree shows the lineages in which BfCBR and CiCBR were identified. It also marks the inferred gene duplication in vertebrates that gave rise to CNR1 and CNR2.

Scientific editorial illustration of the lancelet Branchiostoma floridae on marine sediment
CephalochordataBranchiostoma floridaeSpecies in which BfCBR was identified.
Scientific editorial illustration of the tunicate Ciona intestinalis attached to a rock
TunicataCiona intestinalisSpecies in which CiCBR was identified.
Scientific editorial illustration of the zebrafish Danio rerio as a representative vertebrate
VertebrataDanio rerioRepresentative vertebrate; it is not depicted as an ancestor.
Species tree · gene distribution overlay Selection · chordate common ancestor
Chordate topology with inferred events in the CB1/CB2 family Cephalochordata is sister to Olfactores. Olfactores comprises Tunicata and Vertebrata. BfCBR occurs in Branchiostoma, CiCBR in Ciona, and an inferred duplication in the vertebrate lineage originated CNR1 and CNR2, which encode the CB1 and CB2 receptors. CHORDATA ANCESTRAL CB1/CB2-TYPE RECEPTOR INFERRED Cephalochordata Olfactores Tunicata Vertebrata BfCBR CiCBR CNR1 → CB1 receptor ↗ CNR2 → CB2 receptor divergence between Cephalochordata and Olfactores Tunicata + Vertebrata inferred gene duplication in the vertebrate lineage

Species topology with gene distribution overlay and an inferred duplication; branches do not represent time or genetic distance.

Olfactores is the clade formed by Tunicata and Vertebrata. In this topology, Cephalochordata is its sister group.

Chordate common ancestor

BfCBR and CiCBR indicate an ancestral gene related to CB1 and CB2

BfCBR was identified in Branchiostoma and CiCBR in Ciona. Similarities among these sequences and the vertebrate genes CNR1 and CNR2 indicate that they all descend from a gene present in the common ancestor of chordates. That ancestral gene was not observed directly; its existence is inferred by comparing the evolutionary history of the sequences.

Primary reference Elphick, 2007 ↗

03 · Evidence types

Sequence, expression, and function require distinct evidence

Genomic identification, expression, and functional characterization address different questions and are not interchangeable levels of demonstration.

01

Gene relationships

Sequence comparison and phylogenetic inference support hypotheses about common ancestry, orthology, and paralogy.

phylogenetic evidence
02

Molecular expression

Detection of RNA or protein informs spatial and temporal distribution but does not, in isolation, demonstrate physiological activity.

expression evidence
03

Functional characterization

Assigning function requires appropriate assays, controls, biological context, and evaluation of alternative hypotheses.

experimental evidence
Conceptual illustration of three transmembrane receptors associated with a molecular branching event
Gene-history reconstructionCommon ancestry does not imply complete conservation of function.

04 · Inference and terminology

Receptor function requires multiple evidence layers

Orthology and paralogy describe evolutionary relationships among genes. Robust functional inference and assessment of pharmacological equivalence require integration of sequence, structure, expression, biochemical assays, and comparative physiology.

● observed datum ● evolutionary inference ● unresolved hypothesis
Ortholog Genes in different lineages derived from an ancestral gene through speciation events.
Paralog Genes derived from a duplication event within the same gene history.
Monophyly A group comprising a common ancestor and all of its descendants.
Biological function An activity or role supported by experimental evidence in a defined context.

05 · Bibliographic basis

Studies behind the species tree and receptor-gene interpretation

  1. 01

    Elphick, M. R.; Satou, Y.; Satoh, N. 2003. The invertebrate ancestry of endocannabinoid signalling: an orthologue of vertebrate cannabinoid receptors in the urochordate Ciona intestinalis. Gene, 302(1–2), 95–101.

  2. 02

    Elphick, M. R. 2007. BfCBR: a cannabinoid receptor ortholog in the cephalochordate Branchiostoma floridae. Gene, 399(1), 65–71.

  3. 03

    Delsuc, F. et al. 2006. Tunicates and not cephalochordates are the closest living relatives of vertebrates. Nature, 439, 965–968.

  4. 04

    Putnam, N. H. et al. 2008. The amphioxus genome and the evolution of the chordate karyotype. Nature, 453, 1064–1071.

  5. 05

    Clarke, T. L. et al. 2021. The Endocannabinoid System and Invertebrate Neurodevelopment and Regeneration. International Journal of Molecular Sciences, 22(4), 2103.

  6. 06

    NCBI Taxonomy. Chordata: taxonomic reference record. Accessed 12 September 2026.