Genetic Adaptation and Selenium Uptake in Vertebrates


Nutrients such as iron, zinc, selenium and iodine are needed only in trace amounts but are nevertheless essential to the vertebrate diet. Of these, selenium and iodine are unusual in that their dietary intake depends on their varying content in the soils and waters across the world. Selenium in particular is required due to its function in selenoproteins, which contain the amino acid selenocysteine (the twenty‐first amino acid) as one of their constituent residues. This amino acid is encoded by a termination codon, and its incorporation into selenoproteins is mediated by numerous regulatory proteins. Vertebrate genomes have signatures compatible with adaptation to the different levels of selenium in the world. These signatures are shared among the genes using and regulating selenium and point to past and recent changes to the metabolism and homeostasis of selenium in vertebrate species. Dietary selenium has thus shaped the evolution of vertebrates throughout their history.

Key Concepts

  • Gene annotation. The identification of the location of genes and all of the protein coding regions in the genome. The UGA termination codon in selenoprotein genes makes their annotation difficult.
  • Gene duplication. The duplication of a stretch of DNA that contains a gene. The duplication of selenoprotein genes in fishes is suggestive of new ways to use selenium in protein function as one of the gene copies has evolved much faster than the other.
  • Micronutrient deficiency and toxicity. The lack or excess of one or more of the essential micronutrients in the diet. Selenium in particular has a narrow margin between deficiency and toxicity, and its content in the diet of humans and other vertebrates is often inadequate throughout the world.
  • Polygenic adaptation. The simultaneous selection of alleles at multiple genes. It may have enabled the overall use, metabolism and homeostasis of selenium to adapt to its long‐term variation in the vertebrate diet.
  • Population differentiation. The measurable amount of genetic divergence between two or more groups. Ethnic populations in China living in regions that are selenium deficient have allele at frequencies that differentiate them from other worldwide populations more than expected by neutral evolution.
  • Selenium transport. The transport of selenium atoms in the form of selenocysteine in selenoprotein P from the liver to other tissues via the plasma. The transport of selenium has been under evolutionary constraint (conservation) in fishes, whereas it has evolved neutrally in mammals and other non‐fish lineages.
  • Selenocysteine and cysteine exchangeability. The ability to perform the same function in proteins. The distinct biochemical properties of selenocysteine may explain its low exchangeability with cysteine in vertebrate proteins.
  • Strength of natural selection. The amount of evolutionary constraint on a functional stretch of DNA. Differences in dietary selenium may have resulted in varying strengths of natural selection in vertebrates.

Keywords: micronutrients; selenium; selenocysteine; selenoprotein; deficiency; evolution; natural selection; adaptation; vertebrates; humans

Figure 1. Cartoon view of the loss (by gene deletion, in grey; by selenocysteine to cysteine mutation, in green) and gain (by gene duplication; in red) of selenoprotein genes throughout vertebrate history. The range in the number of selenoprotein genes today is given in parenthesis for each vertebrate clade. Based on Castellano, Andrés, et al. 2009; Mariotti et al. 2012.
Figure 2. Cartoon view of the loss (by selenocysteine to cysteine mutation, in green) and gain (by cysteine to selenocysteine mutation; in red) of selenium atoms in selenoprotein P (SelP) throughout vertebrate history. The number of selenium atoms transported today by SelP is given in parenthesis for each vertebrate clade. Some laurasiatheria are whales, dolphins, pigs, horses, cows, bats, cats, bears, hedgehogs and related species.
Figure 3. Worldwide map of the human populations surveyed in White et al. to assess the patterns of polymorphism in 25 selenoprotein genes, 6 cysteine‐containing genes and 19 genes that are involved in the metabolism and homeostasis of selenium.
Figure 4. Populations from China grouped by whether they live in regions that are selenium deficient or adequate. The selenium‐deficient regions include areas where severe selenium deficiency diseases, such as Keshan disease and Kashin–Beck disease, were endemic in the past. Populations living in the selenium‐deficient regions have allele frequency changes that differentiate them most from other populations.


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Sarangi, Gaurab K, White, Louise, and Castellano, Sergi(May 2017) Genetic Adaptation and Selenium Uptake in Vertebrates. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0026518]