Abstract
Coevolutionary arms races form between interacting populations that constitute each other's environment and respond to mutual changes. This inherently far-from-equilibrium process finds striking manifestations in the adaptive immune system, where highly variable antigens and a finite repertoire of immune receptors coevolve on comparable timescales. This unique challenge to the immune system motivates general questions: How do ecological and evolutionary processes interplay to shape diversity? What determine the endurance and fate of coevolution? Here, we take the perspective of responsive environments and develop a phenotypic model of coevolution between receptors and antigens that both exhibit cross-reactivity (one-to-many responses). The theory predicts that the extent of asymmetry in cross-reactivity is a key determinant of repertoire composition: small asymmetry supports persistent large diversity, whereas strong asymmetry yields long-lived transients of quasispecies in both populations. The latter represents a new type of Turing mechanism. More surprisingly, patterning in the trait space feeds back on population dynamics: spatial resonance between the Turing modes breaks the dynamic balance, leading to antigen extinction or unrestrained growth. Model predictions can be tested via combined genomic and phenotypic measurements. Our work identifies cross-reactivity as an important regulator of diversity and coevolutionary outcome, and reveals the remarkable effect of ecological feedback in pattern-forming systems, which drives evolution toward non-steady states different than the Red Queen persistent cycles.
Highlights
Variable antigenic challengers, such as fast evolving viruses and cancer cells, are rapid in replication and abound with genetic or phenotypic innovations [1,2], managing to evade immune recognition
We show that as asymmetry in cross reactivity varies, transitions between qualitatively distinct regimes of ecoevolutionary dynamics seen in nature would follow, including persistent coexistence, antigen elimination, and unrestrained growth
Extinction is expected when antigens replicate fast but mutate slowly: after a brief delay during which antigen reaches a sufficient prevalence to trigger receptor proliferation, receptors rapidly expand in number and mutate to neighboring types; the pioneer receptors stay ahead of mutating antigens and eliminate them before escape mutants arise
Summary
Variable antigenic challengers, such as fast evolving viruses and cancer cells, are rapid in replication and abound with genetic or phenotypic innovations [1,2], managing to evade immune recognition. The theory predicts, counterintuitively, that simultaneous patterning in coevolving populations can emerge solely from asymmetric range of activation and inhibition in predator-prey dynamics, without a need for severely large differences in their rate of evolution [27] (aka mobility in their common phenotypic space), representing a Turing mechanism distinct from the classic one. This surprising result can be understood from an intuitive picture: colocalized clusters of antigens and receptors form in the trait space when the “inhibition radii” of adjacent receptor clusters overlap so that inhibition of antigen is strongest in-between them; whereas alternate clusters emerge if the “activation radii” of neighboring antigen clusters intersect because activation of receptor is most intense in the midway.
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