Evolutionary progress in the functions of metallothioneins in the ever changing ecosystems

Abstract

Metallothioneins (MTs) exist in various org anisms ranging from some prokaryotes to eukaryotes and mammals. MTs are low molecular weight proteins (MW ranging from 500 to 14000 Da), highly rich in cysteine residues and effectively bind with metals. MTs have the capacity to bind both physiological (such as zinc, copper, selenium) and xenobiotic (such as cadmium, mercury, silver, arsenic) heavy metals through the thiol group of its cysteine residues, which represent nearly 30 % of its constituent amino acid residues. Their combination with heavy metals gives rise to metal-thiolate clusters. It has been suspected that the presence of cysteine in MT is necessary for its functioning and that MT itself is essential for life, modulating complex diseases and the immune system. All different types of MTs are classified with respect to so many factors mainly in groups I and II. There are four main distinguished sub families of the mammalian MT gene families; MT-1 (subtypes A, B, E, F, G, H, L, M, X), MT-2, MT-3, MT-4. They are synthesised primarily in the liver and kidneys. Their production is dependent on availability of the dietary minerals, as zinc, copper and selenium, and the amino acids histidine and cysteine. The rise of these sub families can be attributed to the different functions fulfilled by them. The absence of one defined primary common function could certainly be the reason for serial duplications that gave rise to the respective isoforms. The evolution of MT has been so important to science that they have been considered valid biomarkers in medicine and environmental studies. MT is not limited to the human system, it has also been found in other mammals of the animal kingdom vertebrates (such as the chicken, Gallus gallus, or the mammalian Mus musculus), in higher plants (such as Pisum sativum, Triticum durum, Zea mays, Quercus suber), in protozoa (ex. the ciliate Tetrahymena genera), in yeast (such as Saccharomyces cerevisiae, Candida albicans), in invertebrates (such as the nematode Caenorhabditis elegans, the insect Drosophila melanogaster, the mollusc Mytilus edulis, or the echinoderm Strongylocentrotus purpuratus and in many prokaryotes (such as the cyanobacteria Syneccococus spp). The MTs from this diverse taxonomic range represent a high- heterogeneity sequence (regarding molecular weight and number and distribution of Cys residues) and do not show general homology; in spite of this, homology is found inside some taxonomic groups (such as vertebrate MTs). In this review, we will be looking at the evolution of MTs in respective organisms and the different roles they perform in each of their respective locations in these organisms. We will specifically look at the following factors; evolution of the genetic constitution of MTs and their structural composition and functions.