The Major Histocompatibility Complex (MHC) genes encode proteins that initiate the adaptive immune response by presenting pathogen-derived antigenic peptides to T lymphocytes. Host-pathogen coevolution drives MHC polymorphism, introducing intraspecific variation in host life expectancy. This variation interacts with optimal growth strategy, as growth increases reproductive potential. While mortality rate and body size-dependent fecundity are major factors shaping life histories, the effect of intraspecific variation in MHC-based immunity on the evolution of growth strategies and host body size remains unknown. Here, we model how host MHC–pathogen coevolution—and its concomitant impact on host mortality—can affect the evolution of host life-histories, as represented by age at maturation and body size. Life histories were compared in scenarios with and without adaptive immune response under equal population-level mortality rates. We show that host-pathogen coevolutionary dynamics select for postponed maturation and increased body size. Although MHC genes and genes that determine body size were physically unlinked, selection imposed by the Red Queen process generated linkage disequilibrium between immunocompetent MHC alleles and the maturation-postponing alleles that prolong growth phase and increase body size. Particularly large body size was attained when pathogens mutated slowly, thus allowing the advantage of resistant MHC alleles to persist over multiple generations. The emergence of adaptive immunity, which is pathogen-specific and enables immunological memory, is considered a major evolutionary innovation of vertebrates. Our work suggests that the adaptive immune response, mediated by polymorphic MHC genes, may drive the evolution of host body size. This form of adaptive immunity may have thus predisposed vertebrates to evolve large body sizes and exhibit the macroevolutionary patterns of increasing body size over time that have been detected in comparative studies. 

Data were generated with an individual-based simulation model of host-pathogen co-evolution (see details in Ejsmond et al. Adaptive immune response selects for postponed maturation and increased body size. Functional Ecology). Calculations were performed using resources provided by Wroclaw Centre for Networking and Supercomputing (http://wcss.pl), grant no. 576. We gratefully acknowledge Polish high-performance computing infrastructure PLGrid (HPC Centers: WCSS) for providing computer facilities and support within computational grant no. PLG/2020/013911.

The dataset and the code of the program used in the manuscript "Adaptive immune response selects for postponed maturation and increased body size" published in Functional Biology. The dataset is packed in the ZIP archive 'FunctionalEcology__Ejsmond_et_al_ 2023.zip' and contains the results of the simulation model. The data and the description of variables are stored in the form of Matlab workspace files. The program was implemented and data can be opened with Matlab version 9.1. R2016b or higher.