Amy M Boddy

Arizona State University | ASU

Cancer has deep evolutionary roots and is an important source of selective pressure in organismal evolution. Yet, we find a great deal of variation in cancer vulnerabilities across the tree of life. Comparative oncology offers insights into why some species vary in their susceptibility to cancer and the mechanisms responsible for the diversity of c...

Disease susceptibility and defense are important factors in conservation, particularly for elephants. We report that in addition to endotheliotropic herpesvirus and tuberculosis, Asian elephants are also more susceptible to cancer than African elephants. To determine mechanisms underlying elephant traits including disease resistance, we analyzed ge...

Background and objectives: As the mother-offspring relationship is central to human reproduction, the high incidence of postpartum depression symptoms is difficult to explain in evolutionary terms. We proposed that postpartum depression might be the adverse result of evolutionary mother-offspring conflict over maternal investment, and investigated...

Cancer is a common diagnosis in many mammalian species, yet they vary in their vulnerability to cancer. The factors driving this variation are unknown, but life history theory offers potential explanations to why cancer defense mechanisms are not equal across species. Here we report the prevalence of neoplasia and malignancy in 37 mammalian species...

Metastasis – the ability of cancer cells to disperse throughout the body and establish new tumours at distant locations, is responsible for most cancer‐related deaths. Although both single and clusters of circulating tumour cells (CTCs) have been isolated from cancer patients, CTC clusters are generally associated with higher metastatic potential a...

Despite a considerable expenditure of time and resources and significant advances in experimental models of disease, cancer research continues to suffer from extremely low success rates in translating preclinical discoveries into clinical practice. The continued failure of cancer drug development, particularly late in the course of human testing, n...

The progression of cancer is an evolutionary process. During this process, evolving populations of cancer cells encounter restrictive ecological niches within the body, such as the primary tumor, the circulatory system, and diverse metastatic sites. Heterogeneous populations of cancer cells undergo selection for adaptive phenotypes, which shapes mo...

Purpose In this paper, we provide an overview of a life history theory and how it applies to cancer evolution. Recent Findings We review the literature on trade-offs in tumors, focusing on the trade-offs among cellular proliferation, survival, and motility. Trade-offs are critical natural constraints for almost all evolutionary processes. Many eco...

Some acts of human cooperation are not easily explained by traditional models of kinship or reciprocity. Fitness interdependence may provide a unifying conceptual framework, in which cooperation arises from the mutual dependence for survival or reproduction, as occurs among mates, risk-pooling partnerships and brothers-in-arms.

Increases in organismal complexity come at the cost of an increased likelihood of developing cancer. As complex multicellular organisms evolve, concomitant mechanisms of cancer suppression evolve as well. Over the evolutionary timescale, organisms with the ability to renew somatic tissue needed to evolve tumor suppressor mechanisms to regulate and...

The risk of developing cancer should theoretically increase with both the number of cells and the lifespan of an organism. However, gigantic animals do not get more cancer than humans, suggesting that super-human cancer suppression has evolved numerous times across the tree of life. This is the essence and promise of Peto’s Paradox. We discuss what...

Evolution by natural selection is the conceptual foundation for nearly every branch of biology, and increasingly also for biomedicine and medical research. In cancer biology, evolution explains how populations of cells in tumors change over time. It is a fundamental question whether this evolutionary process is driven primarily by natural selection...

Neoplasms change over time through a process of cell-level evolution, driven by genetic and epigenetic alterations. However, the ecology of the microenvironment of a neoplastic cell determines which changes provide adaptive benefits. There is widespread recognition of the importance of these evolutionary and ecological processes in cancer, but to d...

The adaptive significance of human brain evolution has been frequently studied through comparisons with other primates. However, the evolution of increased brain size is not restricted to the human lineage but is a general characteristic of primate evolution. Whether or not these independent episodes of increased brain size share a common genetic b...

The adaptive significance of human brain evolution has been frequently studied through comparisons with other primates. However, the evolution of increased brain size is not restricted to the human lineage but is a general characteristic of primate evolution. Whether or not these independent episodes of increased brain size share a common genetic b...

Intra-tumor heterogeneity drives neoplastic progression by supplying the fuel for natural selection among neoplastic cells. It also complicates screening and treatment of neoplasms. We hypothesize that the degree of intra-tumor heterogeneity in DCIS should predict which tumors are likely to become invasive and metastatic. We initiated a pilot proje...

Cancer suppression is an important feature in the evolution of large and long-lived animals. While some tumor suppression pathways are conserved among all multicellular organisms, others mechanisms of cancer resistance are uniquely lineage specific. Comparative genomics has become a powerful tool to discover these unique and shared molecular adapta...

Whole-genome analyses of human medulloblastomas show that the dominant clone at relapse is present as a rare subclone at primary diagnosis.

Evolution by natural selection is the conceptual foundation for nearly every branch of biology and increasingly also for biomedicine and medical research. In cancer biology, evolution explains how populations of cells in tumors change over time. It is a fundamental question whether this evolutionary process is driven primarily by natural selection...

Biologists have taken the concept of organism largely for granted. However, advances in the study of chimerism, symbiosis, bacterial-eukaryote associations, and microbial behavior have prompted a redefinition of organisms as biological entities exhibiting low conflict and high cooperation among their parts. This expanded view identifies organisms i...

Different breast cancer subtypes may have divergent risk factors. In a recent meta-analysis, Aktipis and colleagues reported that a later age at first birth and fewer total offspring are associated with a higher risk of estrogen-receptor positive (ER+) breast cancer, but not estrogen-receptor negative (ER-) breast cancer. They conclude that the evo...

The presence of fetal cells has been associated with both positive and negative effects on maternal health. These paradoxical effects may be due to the fact that maternal and offspring fitness interests are aligned in certain domains and conflicting in others, which may have led to the evolution of fetal microchimeric phenotypes that can manipulate...

Multicellularity is characterized by cooperation among cells for the development, maintenance and reproduction of the multicellular organism. Cancer can be viewed as cheating within this cooperative multicellular system. Complex multicellularity, and the cooperation underlying it, has evolved independently multiple times. We review the existing lit...

The factors influencing cancer susceptibility and why it varies across species are major open questions in the field of cancer biology. One underexplored source of variation in cancer susceptibility may arise from trade-offs between reproductive competitiveness (e.g. sexually selected traits, earlier reproduction and higher fertility) and cancer de...

Somatic evolution during cancer progression and therapy results in tumour cells that show a wide range of phenotypes, which include rapid proliferation and quiescence. Evolutionary life history theory may help us to understand the diversity of these phenotypes. Fast life history organisms reproduce rapidly, whereas those with slow life histories sh...

Human brain development follows a unique pattern characterized by a prolonged period of postnatal growth and reorganization, and a postnatal peak in glucose utilization. The molecular processes underlying these developmental changes are poorly characterized. The objectives of this study were to determine developmental trajectories of gene expressio...

In comparison with other primate species, humans have an extended juvenile period during which the brain is more plastic. In the current study we sought to examine gene expression in the cerebral cortex during development in the context of this adaptive plasticity. We introduce an approach designed to discriminate genes with variable as opposed to...

GO and Kegg Pathway analyses for probes with greater variance in children than in adults using as reference all genes called present on the array. (XLS)

Genes found to be significant in variance analyses (great variance in children than adults) in both the Harris et al. 2009 (GEO accession: GSE13564) and current datasets. (CSV)

Intersection of 302 genes with greater variance in children with Mammalian Genome Informatics dataset of Mammalian Phenotype ID: MP:0003631 and MP:0005386). (XLS)

Probes with greater variance in expression in children than in adults. (XLS)

Paired differences between the standard deviation of genes in children vs. adults. The boxplot is made from for all 1020 probes with highest variance across all samples in the postmortem dataset. Positive values indicate larger standard deviation in the younger group (children <15 years), whereas negative values indicate larger standard deviation i...

GO and Kegg Pathway analyses for probes with greater variance in children than in adults using as reference the top 5% of genes with highest variance. (XLS)

Gene Ontology analyses. GO term (Molecular Function and Cellular Component) analyses for probes with greater variance in childhood than in adulthood using as reference all genes called present on the array. The expected number of genes is the number of genes predicted for this term by random chance. The observed number of genes is the number of gen...

Sample information for all individuals. (XLSX)

GO analysis for probes with greater variance in children than adults. (Harris et al., 2009 Dataset; GEO accession: GSE13564). (XLS)

There is a well-established allometric relationship between brain and body mass in mammals. Deviation of relatively increased brain size from this pattern appears to coincide with enhanced cognitive abilities. To examine whether there is a phylogenetic structure to such episodes of changes in encephalization across mammals, we used phylogenetic tec...

The goal of this study was to investigate the role of complement cascade genes in the pathobiology of human abdominal aortic aneurysms (AAAs). Results of a genome-wide microarray expression profiling revealed 3274 differentially expressed genes between aneurysmal and control aortic tissue. Interestingly, 13 genes in the complement cascade were sign...

Inhibitory interneurons participate in local processing circuits, playing a central role in executive cognitive functions of the prefrontal cortex. Although humans differ from other primates in a number of cognitive domains, it is not currently known whether the interneuron system has changed in the course of primate evolution leading to our specie...

Abdominal aortic aneurysms (AAAs) are a complex disease with a late age at onset. Causing approximately 15,000 deaths per year, AAAs are among the top twenty leading causes of death in the United States. A main reason for the high mortality rate of AAAs is that most are asymptomatic until rupture. Local inflammation of the aorta, fragmentation of t...

The goal of this project was to identify genetic variants associated with abdominal aortic aneurysms (AAAs). A genome wide association study was carried out using pooled DNA samples from 123 AAA cases and 112 controls matched for age, gender, and smoking history using Affymetrix 500K single nucleotide polymorphism (SNP) arrays (Affymetrix, Inc, San...

Abdominal aortic aneurysm (AAA) is a complex multifactorial disease with life-threatening implications. Aneurysms typically have no signs or symptoms, and rupture of AAA has a high mortality rate. Multiple environmental and genetic risk factors are involved in aneurysm formation and progression making it a complicated disease to study. Little is un...