# Structural Biochemistry/Biochemical Natural Selection
## Essentiality of Aluminum and Silicon
### Darwin, natural selection and the biological essentiality of aluminum and silicon

By definition, natural selection is a competition in which winners and losers are defined by selection pressures which act upon competitors that are constrained within specific boundaries or arenas. Through experimentation and discovery, it has been assessed that natural selection can be viewed as a force of nature which is as important in biochemical evolution as it is in speciation. Exley takes a closer look at the biological essentiality of both aluminum and silicon. Aluminum in particular is deemed critical and also the most widely abundant metal on earth. In fact, it is the third most abundant element in the Earth’s crust. However, an element’s wide abundance does not correlate with its biological importance. Instead, aluminum is severely hindered by its biological unavailability. Selection of essential metals for biological use is mainly based on several factors including reaction kinetics and reaction thermodynamics. For example, kinetic constraints involve how a biochemical reaction comes to equilibrium which dictate reaction kinetics and ultimately which biochemical pathways are most efficient or favorable and thus predominate. Equilibrium constants dictate properties of reaction products by ways of solubility equilibrium and complex stability.Living systems however concentrate on the importance of kinetics rather than thermodynamics. Specifically kinetics rely on concentration of reactants, products, competitors, and interferences which all aid living systems in its attempt to avoid chemical equilibrium. Thus, kinetics affect the natural selection of which metals become essential to living systems.

#### Natural Selection of Aluminum

This takes us to a more enhanced view at the metal of aluminum. Despite its abundance, it has no essential role in any biological system in an organism. Silicon, on the other hand, is second most abundant, but is indeed viewed as an essential element. It was later found evident that aluminum’s lack of an indispensable biological role could be attributed to its non-participation in addition to the possibility of simply being selected out of systems altogether. The absence of aluminum is actually quite unfortunate, due to its versatility as a biologically reactive element. With further investigation, it was deemed that the lack of aluminum was not because it was selected out of biochemical systems but because the lack of available biologically-reactive aluminum present for selection. The unavailability of aluminum can be explained by the lack of aluminum in biotic cycles. Less than .001% of aluminum which is cycled through abiotic processes such as rain-fuelled dissolution of mountains, is actually cycled through biotic processes. Even more puzzling is that there are no known biological mechanisms that specifically keep aluminum out from biota, nor are there "biological footprints" left behind in evolutionary encounters with biologically reactive aluminum.
Aluminum has the ability to bind to oxygen-based functional groups, participate in critical redox reactions, and serves the role as an excellent immunogen as an antigen to enable widespread use of particular vaccines. However, aluminum was not selected --due to slow ligand exchange rates. While it is able to bind to oxygen-based functional groups it does not do so quickly enough to efficaciously serve as a metal co-factor for enzymes. Also, the prevalence of the biologically reactive form of Silicon, Silicic acid, reacted with biologically reactive Aluminum Al3+ and thus reduced the amount of Al3+. Exley asserts due to this, other less abundant metals were able to outcompete aluminum.
Exley went on to study salmon, which unveiled an interesting fact about the emergence of silicic acid, which sought out to protect against the toxicity of aluminum. In more familiar terms, it can be said that silicic acid took geochemical control over the availability of aluminum. Silicic acid is the only available biological form of silicon because silicon’s bonds are extremely tough to break and is selected against when it comes to participation in reactions. Silicon is essential, however, but does not possess any biochemical importance. Silicic acid is a weak acid that participates in an interaction with aluminum hydroxide to produce HAS. In doing so, it was successful in significantly reducing the biological availability of aluminum and has further promoted less selection for metals as well. The metals, however, that were selected have been deemed essential. Metals such as Magnesium, Iron, Calcium, Zinc, and Copper have created a cloud over Aluminum’s head, metaphorically, of course. The aluminum environment has lately been progressing through human activities and a sort of biochemical evolution that must account for a biologically reactive aluminum.

#### Non-Selection of Silicon

While aluminum was selected against due to its lack of availability of its biologically reactive form Al3+, Silicon's biologically reactive form Si(OH)4 has always been available for selection. Silicon has been seen in biological systems such as in the form of silicic acid which can pass through permeable biological membranes mimicking water and protecting against the toxicity of Aluminum. However today, there is little evidence in biotic systems to prove the essentiality of silicon to living systems.
While there is no silicon biochemistry, silicon still asserts evolutionary pressures being an essential element to life. However the only form of biologically reactive Silicon exist in the form of Silicic acid. Silicic acid is a polyprotic weak acid which loses its first proton at relatively high pH 10. The majority of biochemical reactions occur around neutral pH which thus limits the bioorganic and bioinorganic chemistry of silicon which only exists as a small neutral molecule.

## Sequence, Structure and Biophysical Properties of Proteins

Environmental pressures can shape the sequence, structure and other properties of proteins. Proteins which occupy extreme environments such as proteins which are present in high temperature environments need to be more stable. This stability is mostly determined by the thermodynamic stability of the protein which is dictated by the energy gap between the native state and the unfolded and/or the misfolded states.
Changes in sequence and structure that affect both native and unfolded states are both observed by thermophilic proteins. Characteristics such as higher compactness, tightly packed secondary structure are observed within these proteins. These features are naturally selected for higher tolerances to thermal environmental pressures.

### Adaptation of Viruses

Viruses are another example to adaptation to extreme environments such as presence outside host cells. However once within a host, they must avoid countermeasures of the host and survive. Virus genomes are usually packed tightly rather than loosely packed. Viruses are also prone to high rates of mutation exemplified by overlapping reading frames in RNA viruses which enable a single mutation to affect more than one protein. Natural selection must select how the protein is packed and thus its sequence and thus the mutational tolerance of the virus. A virus while having a compact protein structure, it is not as compact as thermophilic proteins. While thermophilic proteins are resistant to mutation due to its tightly packed proteins, a virus with looser packed proteins can thus mutate more frequently observed in the high rates of viral mutations.

## Reference

Tokuriki N, Oldfield CJ, Uversky VN, Berezovsky IN, Tawfik DS. Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100,Israel.
Darwin, natural selection and the biological essentiality of aluminium and silicon. Exley C. The Birchall Centre, Lennard-Jones Laboratories, Keele University, Staffordshire, ST5 5BG, UK.