Historical Contingency in a Multigene Family Facilitates Adaptive Evolution of Toxin Resistance.
Novel adaptations must originate and function within an already established genome [1]. As a result, the ability of a species to adapt to new environmental challenges is predicted to be highly contingent on the evolutionary history of its lineage [2-6]. Despite a growing appreciation of the importance of historical contingency in the adaptive evolution of single proteins [7-11], we know surprisingly little about its role in shaping complex adaptations that require evolutionary change in multiple genes. One such adaptation, extreme resistance to tetrodotoxin (TTX), has arisen in several species of snakes through coevolutionary arms races with toxic amphibian prey, which select for TTX-resistant voltage-gated sodium channels (Nav) [12-16]. Here, we show that the relatively recent origins of extreme toxin resistance, which involve the skeletal muscle channel Nav1.4, were facilitated by ancient evolutionary changes in two other members of the same gene family. A substitution conferring TTX resistance to Nav1.7, a channel found in small peripheral neurons, arose in lizards ∼170 million years ago (mya) and was present in the common ancestor of all snakes. A second channel found in larger myelinated neurons, Nav1.6, subsequently evolved resistance in four different snake lineages beginning ∼38 mya. Extreme TTX resistance has evolved at least five times within the past 12 million years via changes in Nav1.4, but only within lineages that previously evolved resistant Nav1.6 and Nav1.7. Our results show that adaptive protein evolution may be contingent upon enabling substitutions elsewhere in the genome, in this case, in paralogs of the same gene family.
Department of Biological Sciences, Virginia Tech, Derring Hall 2125, 1405 Perry Street, Blacksburg, VA 24061, USA. Electronic address: joelmcg@vt.edu.
Joel W
JW
McGlothlin
Department of Biology, University of Virginia, P.O. Box 400328, Charlottesville, VA 22904, USA; Department of Ecology, Evolution, and Behavior, University of Minnesota, 140 Gortner Laboratory, 1479 Gortner Avenue, St. Paul, MN 55108, USA.
Megan E
ME
Kobiela
Department of Biology, University of Nevada, Reno, 1664 North Virginia Street (MS 314), Reno, NV 89557, USA.
Chris R
CR
Feldman
Department of Biology, University of Texas, Arlington, Box 19298, Arlington, TX 76019, USA.
Todd A
TA
Castoe
Department of Biology, Utah State University, Uintah Basin Campus, 320 N. Aggie Boulevard (2000 W.), Vernal, UT 84078, USA.
Shana L
SL
Geffeney
Department of Biology, Utah State University, Uintah Basin Campus, 320 N. Aggie Boulevard (2000 W.), Vernal, UT 84078, USA.
Charles T
CT
Hanifin
Department of Biology, University of Virginia, P.O. Box 400328, Charlottesville, VA 22904, USA.
Gabriela
G
Toledo
Naturalis Biodiversity Center, Darwinweg 2, 2333 CR Leiden, the Netherlands.
Freek J
FJ
Vonk
Institute of Biology Leiden, Leiden University, Sylviusweg 72, 2333 BE Leiden, the Netherlands.
Michael K
MK
Richardson
Department of Biology, Utah State University, 5305 Old Main Hill, Logan, UT 84322, USA.
Edmund D
ED
Brodie
Department of Biological Sciences and Environmental Change Initiative, University of Notre Dame, 109B Galvin Life Sciences, Notre Dame, IN 46556, USA.
Michael E
ME
Pfrender
Department of Biology, University of Virginia, P.O. Box 400328, Charlottesville, VA 22904, USA; Mountain Lake Biological Station, University of Virginia, P.O. Box 400328, Charlottesville, VA 22904, USA.
Edmund D
ED
Brodie
D000220:Adaptation, Biological; D000663:Amphibians; D000818:Animals; D005075:Biological Evolution; D005810:Multigene Family; D011235:Predatory Behavior; D012911:Snakes / Q000235:genetics*; D015222:Sodium Channels / Q000235:genetics*; D013779:Tetrodotoxin
D015222:Sodium Channels; D013779:Tetrodotoxin