Evolutionary Implications of Environmental Toxicant Exposure

Abstract

Homo sapiens have been exposed to various toxins and harmful compounds that change according to various phases of human evolution. Population genetics studies showed that such exposures lead to adaptive genetic changes; while observing present exposures to different toxicants, the first molecular mechanism that confers plasticity is epigenetic remodeling and, in particular, DNA methylation variation, a molecular mechanism proposed for medium-term adaptation. A large amount of scientific literature from clinical and medical studies revealed the high impact of such exposure on human biology; thus, in this review, we examine and infer the impact that different environmental toxicants may have in shaping human evolution. We first describe how environmental toxicants shape natural human variation in terms of genetic and epigenetic diversity, and then we describe how DNA methylation may influence mutation rate and, thus, genetic variability. We describe the impact of these substances on biological fitness in terms of reproduction and survival, and in conclusion, we focus on their effect on brain evolution and physiology.

Keywords: DNA methylation; contaminants; epigenetic mechanisms; evolutionary biology.

Figure 1

Illustrative timeline of the different events that exposed humans to different toxic substances during human evolution. Natural and anthropogenic toxicants, which in turn led to genetic adaptations and epigenetic variability, are reported in green and red, respectively. The effects of modern toxicants on DNA methylation played a key role in shaping the mutation rate, biological fitness (in terms of reproduction and survival), and evolution of the human brain.

Figure 2

Schematic illustration of the difference between the deamination process of unmethylated cytosines, which are converted to uracil, and the deamination process of methylated cytosines, which are converted to thymine. The thicker arrow represents the higher conversion rate of methylated cytosines compared to unmethylated cytosines during the deamination process. The enzyme uracil-DNA glycosylase is able to eliminate uracil and promote DNA repair processes, while it is unable to eliminate thymine, causing the increased mutation rate. C = cytosine; G = guanine; U = uracil; T = thymine; Me = methyl group.

Figure 3

Schematic illustration summarizing the DNA methylation changes in different tissues after exposure to the main toxic agents examined in this review, with particular focus on the effect on Dnmts. The yellow boxes indicate the human studies, while the purple boxes indicate the mouse model studies.