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Abstract Cancer is a disease of multicellularity, observed across the tree of life. In principle, animals with larger body sizes and longer lifespans should be at increased risk of developing cancer. However, there is no strong relationship between these traits and cancer across mammals. Previous studies have proposed that increased copy number of cancer-related genes may enhance the robustness of cancer suppression pathways in long-lived mammals, but these studies have not extended beyond known cancer-related genes. In this study, we conducted a phylogenetic generalized least squares analysis to test for associations between copy number of all protein-coding genes and longevity, body size, and cancer prevalence across 94 species of mammals. In addition to investigating the copy number of individual genes, we tested sets of related genes for a relationship between the aggregated gene copy number of the set and these traits. We did not find strong evidence to support the hypothesis that adaptive changes in gene copy number contribute to the lack of correlation between cancer prevalence and body size or lifespan. However, we found several biological processes where aggregate copy number was associated with malignancy rate. The strongest association was for the gene set relating to transforming growth factor beta, a cytokine that plays a role in cancer progression. Overall, this study provides a comprehensive evaluation of the role of gene copy number in adaptation to body size and lifespan and sheds light on the contribution of gene copy number to variation in cancer prevalence across mammals. 

Abstract The genetic basis of traits shapes and constrains how adaptation proceeds in nature; rapid adaptation can proceed using stores of polygenic standing genetic variation or hard selective sweeps, and increasing polygenicity fuels genetic redundancy, reducing gene re-use (genetic convergence). Guppy life history traits evolve rapidly and convergently among natural high- and low-predation environments in northern Trinidad. This system has been studied extensively at the phenotypic level, but little is known about the underlying genetic architecture. Here, we use four independent F2 QTL crosses to examine the genetic basis of seven (five female, two male) guppy life history phenotypes and discuss how these genetic architectures may facilitate or constrain rapid adaptation and convergence. We use RAD-sequencing data (16,539 SNPs) from 370 male and 267 female F2 individuals. We perform linkage mapping, estimates of genome-wide and per-chromosome heritability (multi-locus associations), and QTL mapping (single-locus associations). Our results are consistent with architectures of many loci of small-effect for male age and size at maturity and female interbrood period. Male trait associations are clustered on specific chromosomes, but female interbrood period exhibits a weak genome-wide signal suggesting a potentially highly polygenic component. Offspring weight and female size at maturity are also associated with a single significant QTL each. These results suggest rapid, repeatable phenotypic evolution of guppies may be facilitated by polygenic trait architectures, but subsequent genetic redundancy may limit gene re-use across populations, in agreement with an absence of strong signatures of genetic convergence from recent analyses of wild guppies.