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Parallel evolution of tetrodotoxin resistance in three voltage-gated sodium channel genes in the garter snake Thamnophis sirtalis.

McGlothlin JW, Chuckalovcak JP, Janes DE, Edwards SV, Feldman CR, Brodie ED, Pfrender ME, Brodie ED - Mol. Biol. Evol. (2014)

Bottom Line: These sites are fixed across populations, suggesting that the resistant peripheral nerves antedate resistant muscle.In contrast, three sodium channels expressed solely in the central nervous system (Nav1.1-1.3) showed no evidence of TTX resistance, consistent with protection from toxins by the blood-brain barrier.Our results demonstrate that the molecular basis of adaptation may be both repeatable across members of a gene family and predictable based on functional considerations.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, Virginia Tech, Blacksburg, VA Department of Biology, University of Virginia joelmcg@vt.edu.

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(A) Amino acid substitutions in the pore regions (or “P-loops”) for six Nav in Thamnophis sirtalis. All sequences are shown relative to rat Nav1.1, with residues involved in TTX binding underlined. Substitutions putatively conferring TTX resistance are shown in red. (B) Locations of putative resistance-conferring substitutions in Nav1.4, 1.6, and 1.7.
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msu237-F2: (A) Amino acid substitutions in the pore regions (or “P-loops”) for six Nav in Thamnophis sirtalis. All sequences are shown relative to rat Nav1.1, with residues involved in TTX binding underlined. Substitutions putatively conferring TTX resistance are shown in red. (B) Locations of putative resistance-conferring substitutions in Nav1.4, 1.6, and 1.7.

Mentions: Sodium channels expressed predominantly in the CNS (Nav1.1–1.3) showed no evidence of TTX resistance evolution (fig. 2). Across all three channels, the amino acid sequence of the four P-loops was identical to the sequence from either rat or lizard. In contrast, all three channels expressed in the periphery (Nav1.4, 1.6, and 1.7) showed evidence of TTX resistance. There was no significant evidence of gene conversion between resistant paralogs, suggesting that TTX resistance initially arose through independent mutational events. However, gene conversion does appear to occur among SCN1–3/9A, which are found on the same chromosome in other amniotes (Zakon et al. 2011). Across these four paralogs, 13 CDS fragments found in seven distinct locations and averaging 120 bp in length showed evidence of gene conversion. Only one of these gene conversion events occurred in a P-loop region, the DI P-loop of SCN2/3A.Fig. 2.


Parallel evolution of tetrodotoxin resistance in three voltage-gated sodium channel genes in the garter snake Thamnophis sirtalis.

McGlothlin JW, Chuckalovcak JP, Janes DE, Edwards SV, Feldman CR, Brodie ED, Pfrender ME, Brodie ED - Mol. Biol. Evol. (2014)

(A) Amino acid substitutions in the pore regions (or “P-loops”) for six Nav in Thamnophis sirtalis. All sequences are shown relative to rat Nav1.1, with residues involved in TTX binding underlined. Substitutions putatively conferring TTX resistance are shown in red. (B) Locations of putative resistance-conferring substitutions in Nav1.4, 1.6, and 1.7.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4209135&req=5

msu237-F2: (A) Amino acid substitutions in the pore regions (or “P-loops”) for six Nav in Thamnophis sirtalis. All sequences are shown relative to rat Nav1.1, with residues involved in TTX binding underlined. Substitutions putatively conferring TTX resistance are shown in red. (B) Locations of putative resistance-conferring substitutions in Nav1.4, 1.6, and 1.7.
Mentions: Sodium channels expressed predominantly in the CNS (Nav1.1–1.3) showed no evidence of TTX resistance evolution (fig. 2). Across all three channels, the amino acid sequence of the four P-loops was identical to the sequence from either rat or lizard. In contrast, all three channels expressed in the periphery (Nav1.4, 1.6, and 1.7) showed evidence of TTX resistance. There was no significant evidence of gene conversion between resistant paralogs, suggesting that TTX resistance initially arose through independent mutational events. However, gene conversion does appear to occur among SCN1–3/9A, which are found on the same chromosome in other amniotes (Zakon et al. 2011). Across these four paralogs, 13 CDS fragments found in seven distinct locations and averaging 120 bp in length showed evidence of gene conversion. Only one of these gene conversion events occurred in a P-loop region, the DI P-loop of SCN2/3A.Fig. 2.

Bottom Line: These sites are fixed across populations, suggesting that the resistant peripheral nerves antedate resistant muscle.In contrast, three sodium channels expressed solely in the central nervous system (Nav1.1-1.3) showed no evidence of TTX resistance, consistent with protection from toxins by the blood-brain barrier.Our results demonstrate that the molecular basis of adaptation may be both repeatable across members of a gene family and predictable based on functional considerations.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, Virginia Tech, Blacksburg, VA Department of Biology, University of Virginia joelmcg@vt.edu.

Show MeSH