Phenotypic Mismatches Reveal Escape from Arms-Race Coevolution

Because coevolution takes place across a broad scale of time and space, it is virtually impossible to understand its dynamics and trajectories by studying a single pair of interacting populations at one time. Comparing populations across a range of an interaction, especially for long-lived species, can provide insight into these features of coevolution by sampling across a diverse set of conditions and histories. We used measures of prey traits (tetrodotoxin toxicity in newts) and predator traits (tetrodotoxin resistance of snakes) to assess the degree of phenotypic mismatch across the range of their coevolutionary interaction. Geographic patterns of phenotypic exaggeration were similar in prey and predators, with most phenotypically elevated localities occurring along the central Oregon coast and central California. Contrary to expectations, however, these areas of elevated traits did not coincide with the most intense coevolutionary selection. Measures of functional trait mismatch revealed that over one-third of sampled localities were so mismatched that reciprocal selection could not occur given current trait distributions. Estimates of current locality-specific interaction selection gradients confirmed this interpretation. In every case of mismatch, predators were “ahead” of prey in the arms race; the converse escape of prey was never observed. The emergent pattern suggests a dynamic in which interacting species experience reciprocal selection that drives arms-race escalation of both prey and predator phenotypes at a subset of localities across the interaction. This coadaptation proceeds until the evolution of extreme phenotypes by predators, through genes of large effect, allows snakes to, at least temporarily, escape the arms race

The Chemical and Evolutionary Ecology of Tetrodotoxin (TTX) Toxicity in Terrestrial Vertebrates

Tetrodotoxin (TTX) is widely distributed in marine taxa, however in terrestrial taxa it is limited to a single class of vertebrates (Amphibia). Tetrodotoxin present in the skin and eggs of TTX-bearing amphibians primarily serves as an antipredator defense and these taxa have provided excellent models for the study of the evolution and chemical ecology of TTX toxicity. The origin of TTX present in terrestrial vertebrates is controversial. In marine organisms the accepted hypothesis is that the TTX present in metazoans results from either dietary uptake of bacterially produced TTX or symbiosis with TTX producing bacteria, but this hypothesis may not be applicable to TTX-bearing amphibians. Here I review the taxonomic distribution and evolutionary ecology of TTX in amphibians with some attention to the origin of TTX present in these taxa

Utilization of a mobile medical van for delivering pediatric care in the bateys of the Dominican Republic

Background Bateys are impoverished areas of housing for migrant Haitian sugar cane workers in the Dominican Republic (DR). In these regions, preventative health care is almost non-existent, public service accessibility is limited, and geographic isolation prevents utilization of care even by those families with resources. Consequently, the development of a viable mobile system is vital to the delivery of acute and preventative health care in this region. Aims This study evaluated an existing mobile medical system. The primary goal was to describe the population served, diseases treated, and resources utilized. A secondary goal was to determine qualitatively an optimal infrastructure for sustainable health care delivery within the bateys. Methods Information on basic demographic data, diagnosis, chronicity of disease, and medications dispensed was collected on all pediatric patients seen in conjunction with an existing mobile medical system over a 3-month period in the DR. Health statistics for the region were collected and interviews were conducted with health care workers (HCWs) and community members on existing and optimal health care infrastructure. Results Five hundred eighty-four pediatric patients were evaluated and treated. Median age was 5 years (range 2 weeks to 20 years), and 53.7% of patients seen were 5 years of age or younger. The mean number of complaints per patient was 2.8 (range 0 to 6). Thirty-six percent (373) of all diagnoses were for acute complaints, and 64% (657) were chronic medical problems. The most common pediatric illnesses diagnosed clinically were gastrointestinal parasitic infection (56.6%), skin/fungal infection (46.2%), upper respiratory tract infections (URIs) (22.8%), previously undiagnosed asthma and allergies (8.2%), and symptomatic anemia (7.2%). Thirty HCWs and community members were interviewed, and all cited the need for similar resources: a community clinic and hospital referral site, health promoters within each community, and the initiation of pediatric training for community HCWs. Conclusion A mobile medical system is a sustainable, efficient mechanism for delivering acute and preventive care in the Haitian bateys of the Dominican Republic. The majority of patients served were 8 years of age or younger with multiple presenting symptoms. A pediatric protocol for identifying the most appropriate drugs and supplies for mobile units in the DR can be created based upon diseases evaluated. Qualitative data from HCWs and community members identified the need for an integrative health care delivery infrastructure and community health promoters versed in pediatric care who can aid in education of batey members and monitor chronic and acute illnesses. We are planning follow-up visits to implement these programs

Data from: Evolutionary history of a complex adaptation: tetrodotoxin resistance in salamanders

Understanding the processes that generate novel adaptive phenotypes is central to evolutionary biology. We used comparative analyses to reveal the history of tetrodotoxin (TTX) resistance in TTX-bearing salamanders. Resistance to TTX is a critical component of the ability to use TTX defensively but the origin of the TTX-bearing phenotype is unclear. Skeletal muscle of TTX-bearing salamanders (modern newts, family: Salamandridae) is unaffected by TTX at doses far in excess of those that block action potentials in muscle and nerve of other vertebrates. Skeletal muscle of non TTX-bearing salamandrids is also resistant to TTX but at lower levels. Skeletal muscle TTX-resistance in the Salamandridae results from the expression of TTX-resistant variants of the voltage-gated sodium channel NaV 1.4 (SCN4a). We identified four substitutions in the coding region of salSCN4a that are likely responsible for the TTX-resistance measured in TTX-bearing salamanders and variation at one of these sites likely explains variation in TTX-resistance among other lineages. Our results suggest that exaptation has played a role in the evolution of the TTX-bearing phenotype and provide empirical evidence that complex physiological adaptations can arise through the accumulation of beneficial mutations in the coding region of conserved proteins

Key for electrophysiology data files

This provides guidance for individual recording file

In Silico Analysis of Tetrodotoxin Binding in Voltage-Gated Sodium Ion Channels from Toxin-Resistant Animal Lineages

Multiple animal species have evolved resistance to the neurotoxin tetrodotoxin (TTX) through changes in voltage-gated sodium ion channels (VGSCs). Amino acid substitutions in TTX-resistant lineages appear to be positionally convergent with changes in homologous residues associated with reductions in TTX block. We used homology modeling coupled with docking simulations to test whether positionally convergent substitutions generate functional convergence at the level of TTX–channel interactions. We found little evidence that amino acids at convergent positions generated similar patterns among TTX-resistant animal lineages across several metrics, including number of polar contacts, polar contact position, and estimates of binding energy. Though binding energy values calculated for TTX docking were reduced for some TTX-resistant channels, not all TTX-resistant channels and not all of our analyses returned reduced binding energy values for TTX-resistant channels. Our results do not support a simple model of toxin resistance where a reduced number of bonds between TTX and the channel protein prevents blocking. Rather models that incorporate flexibility and movement of the protein overall may better describe how homologous substitutions in the channel cause changes in TTX block

Data from: Toxicity and population structure of the Rough-Skinned Newt (Taricha granulosa) outside the range of an arms race with resistant predators

Species interactions, and their fitness consequences, vary across the geographic range of a coevolutionary relationship. This spatial heterogeneity in reciprocal selection is predicted to generate a geographic mosaic of local adaptation, wherein coevolutionary traits are phenotypically variable from one location to the next. Under this framework, allopatric populations should lack variation in coevolutionary traits due to the absence of reciprocal selection. We examine phenotypic variation in tetrodotoxin (TTX) toxicity of the Rough-Skinned Newt (Taricha granulosa) in regions of allopatry with its TTX-resistant predator, the Common Garter Snake (Thamnophis sirtalis). In sympatry, geographic patterns of phenotypic exaggeration in toxicity and toxin-resistance are closely correlated in prey and predator, implying that reciprocal selection drives phenotypic variation in coevolutionary traits. Therefore, in allopatry with TTX-resistant predators, we expect to find uniformly low levels of newt toxicity. We characterized TTX toxicity in northwestern North America, including the Alaskan panhandle where Ta. granulosa occur in allopatry with Th. sirtalis. First, we used microsatellite markers to estimate population genetic structure and determine if any phenotypic variation in toxicity might be explained by historical divergence. We found northern populations of Ta. granulosa generally lacked population structure in a pattern consistent with northern range expansion after the Pleistocene. Next, we chose a cluster of sites in Alaska, which uniformly lacked genetic divergence, to test for phenotypic divergence in toxicity. As predicted, overall levels of newt toxicity were low; however, we also detected unexpected among- and within-population variation in toxicity. Most notably, a small number of individuals contained large doses of TTX that rival means of toxic populations in sympatry with Th. sirtalis. Phenotypic variation in toxicity, despite limited neutral genetic divergence, suggests that factors other than reciprocal selection with Th. sirtalis likely contribute to geographic patterns of toxicity in Ta. granulosa

Newt_TTX.csv

Phenotypic data on newt TTX toxicity