Iron's Irreplaceable Role in Evolution

A fundamental principle of evolution is ‘Survival of the Fittest’. In an ever-changing environment, those who adapt to changing conditions survive. Over-reliance on a resource is unstable, something evolution has disregarded about iron. Involved in DNA replication and repair, used in regulatory proteins for gene expression, iron is intrinsic to the key biochemical processes that make up who we are and the world. Our reliance on this scarce resource is ancestral and goes back to the foundations of life. Originally, on the Earth’s surface, there was a high availability of iron dissolved in the Archaean Oceans. Iron has unique electrochemical properties as an electron donor and a superior catalyst to other major rock-forming elements lending itself well to complex processes necessary for advancing to multicellular life. Nature exploited this abundant ferrous iron, and it became integral to the framework of life: A primary cofactor in enzymes of Earth’s most ancient metabolisms, with the Archaean gene expansion enriched in proteins binding iron involved in electron transport and energy-generating pathways. The bioavailability of iron drove cyanobacteria to evolve porphyrin-based photosynthesis which used iron to synthesise chlorophyll and haem to capture and catalyse light energy. The rise of photosynthesis led to the augmentation of Earth’s oxygen levels; a phenomenon known as the Great Oxygenation Event (GOE). Ironically, this resulted in a marked decrease in soluble, and therefore bioavailable iron, as ferrous was oxidised into ferric, resulting in a mass extinction event. Evolution should dictate that given this newfound scarcity of bioavailable iron, to survive bacteria must adapt and overcome their reliance on iron. Yet, there are just two organisms in the world which do not require iron. The significance of iron means any substitution is worse than the threat of extinction. A selection pressure, iron triggered the evolution of small organic molecules called siderophores. Synthesised by bacteria, they bind to iron in the extracellular environment and chelate it, forming strong complexes, making it bioavailable. They are then recaptured by transporter systems on the surface of bacteria. Siderophores are produced by most modern bacteria (as well as plants and fungi), and this initial development, again pioneered by iron, prompted increasingly complex cell-to-cell interactions. To maximise iron uptake, bacteria formed communities, gathering near sources of iron in spatial structures. They co-operated with each other in iron-capture, regulating siderophore productions to maximise mutual benefit. Others took advantage of this and began to thieve: these bacterial species lost the ability to synthesise their own siderophores but retained the capture-transporter systems to retrieve them, so instead of expending energy on synthesising siderophores, they stole and cheated their way into fulfilling their iron requirements. However, it was when eukaryotic multicellular organisms evolved, requiring iron to function, that the selection pressure determined the behaviours which define us: phagocytosis, endosymbiosis, and infection. These mark the switch in iron acquisition from mineral sources to life-forms. Phagocytosis is a secondary non-specific defence against pathogenic infection. It evolved as a way for eukaryotes to prey on bacteria, engulfing them to absorb their iron content, acting out the role of siderophores on a macroscale. The mechanism of phagocytosis enabled the endosymbiosis of mitochondria. Eukaryotes engulfed alphaproteobacteria by endocytosis but instead of digesting them, they formed a symbiotic relationship with bacteria evolving into mitochondria which facilitated the uptake of iron with specialised iron transporter systems enabling eukaryotic cells to manage iron. Infection materialised as a means for bacteria to maximise their iron supply. Bigger, complex Eukaryota provided bacteria a larger hunting ground for iron, and they evolved the ability to invade cells and release siderophores within organisms to leach the iron out of their cells causing harm. Modern infection’s ties to the decreasing bioavailability of iron still impact us today. Independent lines of genetic evidence and experimental studies show iron assimilation is a critical influence on outcomes of infection: Virulence in bacteria is determined by iron. Lethal bacteria are rendered harmless in the absence of the clusters of genes selected to optimise iron-capture from hosts. From the origins of the earth, iron has pioneered evolution and genetic diversity, and as sources of bioavailable iron continue to deplete, iron will continue to pressure organisms to adapt and evolve, finding new ways to source an irreplaceable resource.