Positive selection in the evolution of cancer

Abstract

We hypothesize that forms of antagonistic coevolution have forged strong links between positive selection at the molecular level and increased cancer risk. By this hypothesis, evolutionary conflict between males and females, mothers and foetuses, hosts and parasites, and other parties with divergent fitness interests has led to rapid evolution of genetic systems involved in control over fertilization and cellular resources. The genes involved in such systems promote cancer risk as a secondary effect of their roles in antagonistic coevolution, which generates evolutionary disequilibrium and maladaptation. Evidence from two sources: (1) studies on specific genes, including SPANX cancer/testis antigen genes, several Y-linked genes, the pem homebox gene, centromeric histone genes, the breast cancer gene BRCA1, the angiogenesis gene ANG, cadherin genes, cytochrome P450 genes, and viral oncogenes; and (2) large-scale database studies of selection on different functional categories of genes, supports our hypothesis. These results have important implications for understanding the evolutionary underpinnings of cancer and the dynamics of antagonistically-coevolving molecular systems.

The androgen receptor and prostate cancer: A role for sexual selection and sexual conflict?

“…If sexual selection and sexual antagonism are generally associated with an increased risk of cancer, then we would expect to find evidence that a variety of genes specifically associated with sexual reproduction would be both implicated in cancer risk and show evidence of positive selection, which is frequently associated with sexual selection, and with antagonistic coevolution [18] (Table 1). A signal of positive selection in comparative analyses of DNA sequences occurs when the ratio non-synonymous to synonymous substitutions exceeds one for all of part of a particular gene [61].…”

“…Steroid hormones and associated proteins are also likely to mediate various forms of sexual antagonism, given that selection is expected to favor functions conducive to early reproduction but harmful to long-term survival more strongly in males than in females [2]. In turn, diverse molecular-genetic and clinical evidence indicates that this type of sexual antagonism, and consequent sexually antagonistic coevolution generates pleiotropic genetic effects that enhance the risk of cancer [18].…”

Mutation-Profile-Based Methods for Understanding Selection Forces in Cancer Somatic Mutations: A Comparative Analysis

“…Since the pioneering work of Cairns and Nowell [1,2], the evolutionary concept of cancer progression has been widely accepted [3][4][5][6][7]. In this model, cancer cells evolve through random somatic mutations and epigenetic changes that may alter several crucial pathways, a process that is followed by clonal selection of the resulting cells.…”

“…Given that many of the positively selected genes in tumor development act as the driving force behind tumor initiation and development and are thus considered "driver genes", it is understandable that almost all previous studies have focused on positively selected genes in cancer genomes [3,[18][19][20][21]. Nevertheless, we have realized that an alternative approach, i.e., identifying cancer-constrained genes that are highly conserved in tumor cell populations (under purifying selection), is also valuable.…”

Evolution of the human lifespan and diseases of aging: Roles of infection, inflammation, and nutrition

“…Of 333 cancer-associated genes, the majority are almost identical in chimpanzees (88,89). The human BRCA1 has an unusual number of Alu repeats that cause gene instability, whereas the chimpanzee BRCA1 has an 8-kb deletion that truncates the coregulated NBR2 gene.…”