GEPHE SUMMARY
Gephebase Gene
Entry Status
Published
GepheID
GP00000699
Main curator
Courtier
PHENOTYPIC CHANGE
Trait Category
Trait State in Taxon A
Eleven Varanus species - sensitive
Trait State in Taxon B
other Varanus species - resistant
Ancestral State
Taxon A
Taxonomic Status
Taxon A #1
Common Name
-
Synonyms
Varanus tristis (Schlegel, 1839); RMNH 3858; RMNH:3858
Rank
species
Lineage
Show more ... gii; Dipnotetrapodomorpha; Tetrapoda; Amniota; Sauropsida; Sauria; Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera; Anguimorpha; Paleoanguimorpha; Varanoidea; Varanidae; Varanus
NCBI Taxonomy ID
is Taxon A an Infraspecies?
No
Taxon A #2
Common Name
-
Synonyms
SAMA R3230
Rank
species
Lineage
Show more ... gii; Dipnotetrapodomorpha; Tetrapoda; Amniota; Sauropsida; Sauria; Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera; Anguimorpha; Paleoanguimorpha; Varanoidea; Varanidae; Varanus
NCBI Taxonomy ID
is Taxon A an Infraspecies?
No
Taxon A #3
Common Name
-
Synonyms
SMF 32806; SMF:32806
Rank
species
Lineage
Show more ... gii; Dipnotetrapodomorpha; Tetrapoda; Amniota; Sauropsida; Sauria; Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera; Anguimorpha; Paleoanguimorpha; Varanoidea; Varanidae; Varanus
NCBI Taxonomy ID
is Taxon A an Infraspecies?
No
Taxon B #1
Common Name
water monitor
Synonyms
Hydrosaurus salvator; Stellio salvator; water monitor; Varanus salvator (Laurenti, 1768); ZFMK 22092; ZFMK:22092
Rank
species
Lineage
Show more ... gii; Dipnotetrapodomorpha; Tetrapoda; Amniota; Sauropsida; Sauria; Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera; Anguimorpha; Paleoanguimorpha; Varanoidea; Varanidae; Varanus
NCBI Taxonomy ID
is Taxon B an Infraspecies?
No
Taxon B #2
Common Name
-
Synonyms
Nile monitor; Nile monitor lizard; Varanus niloticus (Linnaeus, 1766); NRM 9185; NRM:9185
Rank
species
Lineage
Show more ... gii; Dipnotetrapodomorpha; Tetrapoda; Amniota; Sauropsida; Sauria; Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera; Anguimorpha; Paleoanguimorpha; Varanoidea; Varanidae; Varanus
NCBI Taxonomy ID
is Taxon B an Infraspecies?
No
Taxon B #3
Common Name
cape monitor
Synonyms
Varanus exanthematicus albigularis; cape monitor; Varanus albigularis (Daudin, 1802); Varanus exanthematicus albigularis Schmidt, 1919; MNHN 6513; MNHN:6513
Rank
species
Lineage
Show more ... gii; Dipnotetrapodomorpha; Tetrapoda; Amniota; Sauropsida; Sauria; Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera; Anguimorpha; Paleoanguimorpha; Varanoidea; Varanidae; Varanus
NCBI Taxonomy ID
is Taxon B an Infraspecies?
No
GENOTYPIC CHANGE
Generic Gene Name
Atp1a1
Synonyms
Atpa-1; BC010319
Sequence Similarities
Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIC subfamily.
UniProtKB
Mus musculus
GenebankID or UniProtKB
Mutation #1
Presumptive Null
No
Molecular Type
Aberration Type
SNP
SNP Coding Change
Nonsynonymous
Molecular Details of the Mutation
Q111L
Experimental Evidence
Taxon A Taxon B Position
Codon - - -
Amino-acid Gln Leu 111
Authors
Ujvari B; Casewell NR; Sunagar K; Arbuckle K; Wüster W; Lo N; O'Meally D; Beckmann C; et al. ... show more
Abstract
The question about whether evolution is unpredictable and stochastic or intermittently constrained along predictable pathways is the subject of a fundamental debate in biology, in which understanding convergent evolution plays a central role. At the molecular level, documented examples of convergence are rare and limited to occurring within specific taxonomic groups. Here we provide evidence of constrained convergent molecular evolution across the metazoan tree of life. We show that resistance to toxic cardiac glycosides produced by plants and bufonid toads is mediated by similar molecular changes to the sodium-potassium-pump (Na(+)/K(+)-ATPase) in insects, amphibians, reptiles, and mammals. In toad-feeding reptiles, resistance is conferred by two point mutations that have evolved convergently on four occasions, whereas evidence of a molecular reversal back to the susceptible state in varanid lizards migrating to toad-free areas suggests that toxin resistance is maladaptive in the absence of selection. Importantly, resistance in all taxa is mediated by replacements of 2 of the 12 amino acids comprising the Na(+)/K(+)-ATPase H1-H2 extracellular domain that constitutes a core part of the cardiac glycoside binding site. We provide mechanistic insight into the basis of resistance by showing that these alterations perturb the interaction between the cardiac glycoside bufalin and the Na(+)/K(+)-ATPase. Thus, similar selection pressures have resulted in convergent evolution of the same molecular solution across the breadth of the animal kingdom, demonstrating how a scarcity of possible solutions to a selective challenge can lead to highly predictable evolutionary responses.
Additional References
Mutation #2
Presumptive Null
No
Molecular Type
Aberration Type
SNP
SNP Coding Change
Nonsynonymous
Molecular Details of the Mutation
G120R
Experimental Evidence
Taxon A Taxon B Position
Codon - - -
Amino-acid Gly Arg 120
Authors
Ujvari B; Casewell NR; Sunagar K; Arbuckle K; Wüster W; Lo N; O'Meally D; Beckmann C; et al. ... show more
Abstract
The question about whether evolution is unpredictable and stochastic or intermittently constrained along predictable pathways is the subject of a fundamental debate in biology, in which understanding convergent evolution plays a central role. At the molecular level, documented examples of convergence are rare and limited to occurring within specific taxonomic groups. Here we provide evidence of constrained convergent molecular evolution across the metazoan tree of life. We show that resistance to toxic cardiac glycosides produced by plants and bufonid toads is mediated by similar molecular changes to the sodium-potassium-pump (Na(+)/K(+)-ATPase) in insects, amphibians, reptiles, and mammals. In toad-feeding reptiles, resistance is conferred by two point mutations that have evolved convergently on four occasions, whereas evidence of a molecular reversal back to the susceptible state in varanid lizards migrating to toad-free areas suggests that toxin resistance is maladaptive in the absence of selection. Importantly, resistance in all taxa is mediated by replacements of 2 of the 12 amino acids comprising the Na(+)/K(+)-ATPase H1-H2 extracellular domain that constitutes a core part of the cardiac glycoside binding site. We provide mechanistic insight into the basis of resistance by showing that these alterations perturb the interaction between the cardiac glycoside bufalin and the Na(+)/K(+)-ATPase. Thus, similar selection pressures have resulted in convergent evolution of the same molecular solution across the breadth of the animal kingdom, demonstrating how a scarcity of possible solutions to a selective challenge can lead to highly predictable evolutionary responses.
Additional References
RELATED GEPHE
Related Genes
No matches found.
Related Haplotypes
1
COMMENTS
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