Microbial mercury methylation: a detoxifying defense or an antimicrobial advantage?

Methylmercury (MeHg) is a potent neurotoxin that damages brain tissue, particularly impacting the neural development of mammalian prenatal infants1. In the environment, it is produced almost entirely by microorganisms from industrial mercury (Hg) pollution (e.g., fossil fuel combustion, chemicals production, mining) that travels through the atmosphere or via surface waterways to accumulate on land and in the sea2. Some of this mercury has been accumulating in environments like peatlands for centuries to millennia, beginning with atmospheric emissions from Roman-era mining3. The latest climate change models predict that warming global temperatures will accelerate microbial mercury methylation in sediments and seawater4. Methylmercury concentrations build up ("biomagnify") in marine and land food webs to present health hazards for humans and animals. The primary source of methylmercury poisoning to humans is fish, from which roughly one-third of the world's population, including the most economically poor, obtains at least 20% of its dietary protein5. More recently, however, it was discovered that methylmercury produced in rice paddies can be directly uptaken by some rice plants as well6, presenting a potentially even more serious ecotoxicological threat to human health. Despite over a half-century of research, we still do not understand how or why some microbes in the environment make methylmercury, thus undermining our ability to predict and mitigate methylmercury production in nature. However, recent discoveries have begun to uncover some vital clues. For example, we have found that mercury methylation seems to have some genetic link to the microbe's ability to mitigate arsenic toxicity7,8. We have also discovered that the genes encoding for mercury methylation date back to the last common ancestor of the bacteria and archaea9. In the context of these and other recent insights, we aim here to decode the genetic evolution and expression "triggers" for mercury methylation, in order to understand its genetic pre-requisites and environmental pre-conditions. Specifically, we will use carefully designed bacterial culturing experiments to test several hypotheses: 1) Hg methylation originated as an antimicrobial (i.e. antibiotic) function against other microbes in competition for food, 2) Hg methylation gene expression is linked genetically to arsenic resistance gene expression, 3) Hg methylation requires an anabolic metabolic pathway, 4) Hg methylation involves a catabolic metabolic pathway. We will also perform advanced bioinformatic analyses to unravel the evolutionary timings of genes encoding for mercury methylation, single-carbon metabolism and arsenic resistance. We hypothesize here: 5) arsenic resistance genes predated, and may have been co-opted for, mercury methylation, and 6) co-evolution of other metal resistance genes and mercury methylation genes, along with subsequent gene loss events and lateral transfers, can explain the complex distribution of mercury methylation capabilities across the Tree of Life, one of the most perplexing and long-lasting mysteries in this field. Importantly, the results of our experiments and analyses will give us new answers and insights into which environments and conditions promote mercury methylation and therefore how we might develop more effective interventions to protect environmental health, water quality and food security. In that regard, this proposal represents both fundamental "discovery" bioscience that will yield new knowledge into how microbes have evolved to function (i.e. the "Rules to Life") as well as interdisciplinary and applied "Molecules to Landscape"-facing research for protecting food security and reducing methylmercury pollution on land and at sea.