(Co)evolution at the interface of species interactions

All organisms on earth interact with other species. Interspecific interactions are a major driver of adaptation and the evolution of biodiversity. Undergraduate students in the Hague lab study the coevolution of host-microbe and predator-prey relationships. We drill down to the cellular-genetic interface of these species interactions in order to understand broader patterns of coevolution and ecological diversity.

Hosts &
Microbes

Hosts and Microbes illustration

Predators &
Prey

Predators and Prey illustration

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Research

A cellular-genetic basis for endosymbiont prevalence

Endosymbioses are intimate host-microbe relationships where bacteria reside within the cells of their host. Endosymbionts alter basic aspects of host biology, evolution, and ecology. We study the spread and evolution of Wolbachia, the most common endosymbionts in nature. Wolbachia infect about half of all insect species and biocontrol programs employ virus-blocking Wolbachia to prevent mosquitoes from transmitting deadly diseases like dengue. Our research goal is to understand how cellular host-microbe interactions determine global Wolbachia prevalence and coevolution with hosts.

Wolbachia in Drosophila oocyte
wMel transmission figure

Transmission rates explain Wolbachia prevalence

The prevalence of Wolbachia and other endosymbionts varies widely across environments and insect species. Wolbachia are vertically transmitted from mother to offspring; however, this process can break down under certain conditions. I found that cold temperatures perturb maternal Wolbachia transmission in host oocytes, which provides a simple explanation for why Wolbachia are less prevalent at temperate latitudes in Drosophila melanogaster fruit fly populations. Genomic analyses and crossing experiments suggest that Wolbachia and hosts from southern Australia have rapidly co-adapted to the temperate climate in only the last ~5,000 years. Wolbachia strains found in other Drosophila species show varying levels of thermal sensitivity, which may help explain why Wolbachia are common in some insect species but not others.

symbiontmodeler figure

Endosymbiont prevalence fluctuates over time

A small host population can give rise to stochastic fluctuations of endosymbiont frequencies from one host generation to the next. Building on well-established theory, we implemented mathematical models of endosymbiont spread in the publicly available R package symbiontmodeler. Researchers and students can use the package to investigate how factors like host population size contribute to endosymbiont fluctuations over time. Our simulations show that maternal transmission rates play an outsized role in determining the size of stochastic fluctuations in finite host populations.

comparative data figure

Endosymbionts alter host fitness

Endosymbionts can have complex effects on the physiology, behavior, and fitness of their hosts. Wolbachia bacteria are found throughout many insect tissues (e.g., the brain), yet we have a poor understanding of how somatic infections affect host fitness. Using a comparative approach, we've found that Wolbachia have pervasive effects on basic aspects of insect physiology and behavior. The work has demonstrated that diverse Wolbachia strains diverged up to 50 million years ago alter the activity levels and thermal preference of their Drosophila hosts.

Evolution of prey toxins and predator resistance

Intense coevolution between natural enemies like predators and prey can lead to an arms race. I study adaptation at the molecular interface of toxin-binding in the coevolutionary arms race between garter snakes and their deadly prey, Pacific newts. The work examines how protein evolution and constraints shape escalation of the arms race across western North America.

Garter snake
Nav1.4 figure

Convergent evolution of a conserved protein

Arms race coevolution drives rapid adaptation and counter-adaptation, but functional trade-offs may also develop as a consequence. I found that multiple lineages of garter snakes independently evolved resistance to tetrodotoxin (TTX) via a repeated first-step mutation to the Nav1.4 skeletal muscle sodium channel that disrupts toxin-binding, implying that increases in resistance depend on an initial permissive mutation. In highly resistant snakes, accumulating mutations in the channel pore disrupt toxin-binding, but also generate negative trade-offs with Nav1.4 function and muscle performance. These results highlight how costs develop as beneficial mutations accumulate in the arms race. Constraints in Nav1.4 evolution help explain the convergent evolution of TTX resistance in multiple snake populations across western North America.

Geographic mosaic of coevolution

Asymmetries in the arms race

Reciprocal adaptation is the hallmark of coevolution, but the evolutionary response of each species may not be symmetrical. Levels of snake resistance and newt toxins are closely matched across western North America, implying that phenotypic escalation in both species is a result of the arms race. Geographic variation in snake TTX resistance shows a clear signature of local adaptation to toxic prey. However, I found that geographic variation in newt toxin levels is best explained by the spatial structure of newt populations, not snake resistance. This unexpected result suggests that neutral processes like gene flow — rather than reciprocal adaptation — represent the greatest source of variation across the geographic mosaic of coevolution.

Publications

Undergraduate co-authors are marked with an asterisk (*). A complete list of papers is available on Google Scholar.

Graham, JM, J Klobusicky, MTJ Hague. 2025. Stochastic fluctuations of the facultative endosymbiont Wolbachia due to finite host population size. Ecology & Evolution. 15: e71989 [link]

Hague, MTJ, TB Wheeler, BS Cooper. 2024. Comparative analysis of Wolbachia maternal transmission and localization in host ovaries. Communications Biology. 7: 727 [link]

del Carlo, RE, JS Reimche, HA Moniz, MTJ Hague, SR Agarwal, ED Brodie III, ED Brodie, Jr., N Leblanc, CR Feldman. 2024. Coevolution with toxic prey produces functional trade-offs in sodium channels of predatory snakes. eLife. 13: RP94633 [link]

Gilbert, AL, S Cabrera, MTJ Hague, AN Stokes, CR Feldman, CT Hanifin, ED Brodie, Jr., ED Brodie III. 2023. Climate and community predict landscape outcomes of predator-prey coevolution. Functional Ecology. 37: 2170-2180 [link]

Radousky, YA, MTJ Hague, S Fowler, E Paneru*, A Codina*, C Rugamas*, G Hartzog, BS Cooper, W Sullivan. 2023. Distinct Wolbachia localization patterns in oocytes of diverse host species reveal multiple strategies of maternal transmission. GENETICS. 224: iyad038 [link]

Hague, MTJ, LE Miller*, AN Stokes, CR Feldman, ED Brodie, Jr., ED Brodie III. 2022. Conspicuous coloration of toxin-resistant predators implicates additional trophic interactions in a predator-prey arms race. Molecular Ecology (From the Cover). 32 [link]

Profiled in Molecular Ecology Perspective: Thompson, JN. 2023. The ripple effects of clines from coevolutionary hotspots to coldspots. Molecular Ecology. 32 [link]

Hague, MTJ, JD Shropshire, CN Caldwell*, JP Statz, KA Stanek, WR Conner, BS Cooper. 2022. Temperature effects on cellular host-microbe interactions explain continent-wide endosymbiont prevalence. Current Biology. 32: 878-888 [link]

Profiled in Current Biology Dispatch: Stuckert, AMM, DR Matute. 2022. Evolution: Environmental conditions determine how Wolbachia interacts with hosts. Current Biology. 32: R178–R180 [link]

Gendreau, KL, AD Hornsby, MTJ Hague, JW McGlothlin. 2021. Gene conversion facilitates the adaptive evolution of self-resistance in highly toxic newts. Molecular Biology and Evolution. 38: 4077-4094 [link]

Hague, MTJ, HA Woods, BS Cooper. 2021. Pervasive effects of Wolbachia on host activity. Biology Letters. 17: 20210052 [link]

Hague, MTJ, CN Caldwell*, BS Cooper. 2020. Pervasive effects of Wolbachia on host temperature preference. mBio. 11: e01768-20 [link]

Hague, MTJ, H Mavengere, DR Matute, BS Cooper. 2020. Environmental and genetic contributions to imperfect wMel-like Wolbachia transmission and frequency variation. GENETICS. 215: 1117-1132 [link]

Hague, MTJ, AN Stokes, CR Feldman, ED Brodie, Jr., ED Brodie III. 2020. The geographic mosaic of arms race coevolution is closely matched to prey population structure. Evolution Letters. 4: 317-332 [link]

Gendreau, KL, MTJ Hague, CR Feldman, ED Brodie, Jr., ED Brodie III, JW McGlothlin. 2020. Sex linkage of the skeletal muscle sodium channel gene (SCN4A) explains apparent deviations from Hardy-Weinberg equilibrium of tetrodotoxin-resistance alleles in garter snakes (Thamnophis sirtalis). Heredity. 124: 647-657 [link]

Featured on the Heredity podcast: "Resistance is female" [link]

Hague, MTJ, G Toledo, SL Geffeney, CT Hanifin, ED Brodie, Jr., ED Brodie III. 2018. Large-effect mutations generate trade-off between predatory and locomotor ability during arms race coevolution with deadly prey. Evolution Letters. 2: 406-416 [link]

Profiled in Evolution Letters Editor's Blog: "Trading off resistance and speed in a deadly arms race" [link]

Hague, MTJ, CR Feldman, ED Brodie, Jr., ED Brodie III. 2017. Convergent adaptation to dangerous prey proceeds through the same first-step mutation in the garter snake Thamnophis sirtalis. Evolution. 71: 1504-1518 [link]

Profiled in Evolution Digest: Davies, KTJ. 2017. Know your poison: Predictable molecular changes confer toxin resistance in snakes? Evolution. 71: 1728–1729 [link]

Hague, MTJ, LA Avila, CT Hanifin, WA Snedden, AN Stokes, ED Brodie, Jr., ED Brodie III. 2016. Toxicity and population structure of the Rough-Skinned Newt (Taricha granulosa) outside the range of an arms race with resistant predators. Ecology & Evolution. 6: 2714-2724 [link]

Hague, MTJ, EJ Routman. 2015. Does population size affect genetic diversity? A test with sympatric lizard species. Heredity. 116: 92-98 [link]

Eads, DA, MTJ Hague, CG Zoubek. 2012. American badger (Taxidea taxus) uses covert reconnaissance from tire-ruts to ambush a black-tailed prairie dog (Cynomys ludovicianus). Southwestern Naturalist. 57: 463-464 [link]

People
Michael Hague

Michael T.J. Hague, PhD

Assistant Professor
michael.hague@scranton.edu
570-941-7962
Office: LSC 374
Biology Department
University of Scranton
Scranton, PA 18510
Olivia Enderle

Olivia Enderle

Class of 2026
Biology major
Lex Martinez

Lex Martinez

Class of 2026
BCMB major
Magis Honors Program
Kate McKillop

Kate McKillop

Class of 2027
Biology major
Magis Honors Program
Holly Zaluski

Holly Zaluski

Class of 2028
BCMB major
SJLA and Magis Honors Programs

Interested in Joining?

My lab at the University of Scranton is just getting started! I'm excited to collaborate with new students and I value diversity of ideas, experiences, and backgrounds. If you're interested in joining the lab, email me your resume and a paragraph describing your research interests.

Hague Lab Graduates

Gavin Kopesky (class of 2025, University Honors)
Drew Dickson (class of 2025)