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. ; Mariotti et al. .
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.


Ahmad K, Khan ZI, Ashraf M, et al. (2009) Time‐course chages in selenium status of soil and forage in a pasture in Sargodha, Punjab, Pakistan. Pakistan Journal of Botany 41: 2397–2401.

Bekaert M, Firth AE, Zhang Y, et al. (2010) Recode‐2: new design, new search tools, and many more genes. Nucleic Acids Research 38: D69–D74.

Berry MJ, Banu L, Harney JW and Larsen PR (1993) Functional characterization of the eukaryotic SECIS elements which direct selenocysteine insertion at UGA codons. The EMBO Journal 12 (8): 3315–3322.

Berzelius JJ (1818) Lettre de M. Berzelius à M. Berthollet sur deux métaux nouveaux. Annales de chimie et de physique, series 2 (7): 199–206.

Castellano S, Gladyshev VN, Guigó R and Berry MJ (2008) SelenoDB 1.0: a database of selenoprotein genes, proteins and SECIS elements. Nucleic Acids Research 36: D339–D343.

Castellano S, Andrés AM, Bosch E, et al. (2009) Low exchangeability of selenocysteine, the 21st amino acid, in vertebrate proteins. Molecular Biology and Evolution 26 (9): 2031–2040.

Cavalli‐Sforza LL (2005) The human genome diversity project: past, present and future. Nature Reviews Genetics 6 (4): 333–340.

Chambers I, Frampton J, Goldfarb P, et al. (1986) The structure of the mouse glutathione peroxidase gene: the selenocysteine in the active site is encoded by the 'termination' codon, TGA. The EMBO Journal 5 (6): 1221–1227.

Dudley HC (1938) Selenium as a potential industrial hazard. Public Health Reports 53 (8): 281–292.

Flueck WT (2015) Osteopathology and selenium deficiency co‐occurring in a population of endangered Patagonian huemul (Hippocamelus bisulcus). BMC Research Notes 8: 330.

Fu Q, Mittnik A, Johnson PL, et al. (2013) A revised timescale for human evolution based on ancient mitochondrial genomes. Current Biology 23: 553–559.

Gromer S, Johansson L, Bauer H, et al. (2003) Active sites of thioredoxin reductases: why selenoproteins? 100 (22): 12618–12623.

Gromer S, Eubel JK, Lee BL and Jacob J (2005) Human selenoproteins at a glance. Cellular and Molecular Life Sciences 62 (21): 2414–2437.

Hawkes WC and Tappel AL (1983) In vitro synthesis of glutathione peroxidase from selenite. Translational incorporation of selenocysteine. Biochimica et Biophysica Acta 699 (3): 183–191.

Hogstrand Christer and Maret Wolfgang (2016) Genetics of Human Zinc Deficiencies. In: eLS Chichester: John Wiley & Sons Ltd.

Itan Y, Powell A, Beaumont MA, Burger J and Thomas MG (2009) The origins of lactase persistence in Europe. PLoS Computational Biology 5 (8): e1000491.

Johnson CC, Fordyce FM and Rayman MP (2010) Symposium on 'Geographical and geological influences on nutrition': Factors controlling the distribution of selenium in the environment and their impact on health and nutrition. Proceedings of the Nutrition Society 69 (1): 119–132.

Kasaikina MV, Hatfield DL and Gladyshev VN (2012) Understanding selenoprotein function and regulation through the use of rodent models. Biochimica et Biophysica Acta 1823 (9): 1633–1642.

Khan ZI, Hussain A, Ashraf M and McDowell R (2006) Mineral status of soils and forages in southwestern Punjab‐Pakistan: micro‐minerals. Asian‐Australasian Journal of Animal Sciences 19: 1139–1147.

Khan ZI, Ashraf M, Danish M, Ahmad K and Valeem EE (2008) Assessment of selenium content in pasture and ewes in Punjab, Pakistan. Pakistan Journal of Botany 40: 1159–1162.

Kim YY and Mahan DC (2003) Biological aspects of selenium in farm animals. Asian‐Australasian Journal of Animal Sciences 16 (3): 435–444.

Kryukov GV, Kryukov VM and Gladyshev VN (1999) New mammalian selenocysteine‐containing proteins identified with an algorithm that searches for selenocysteine insertion sequence elements. Journal of Biological Chemistry 274 (48): 33888–33897.

Kryukov GV, Castellano S, Novoselov SV, et al. (2003) Characterization of mammalian selenoproteomes. Science 300 (5624): 1439–1443.

Lescure A, Gautheret D, Carbon P and Krol A (1999) Novel selenoproteins identified in silico and in vivo by using a conserved RNA structural motif. Journal of Biological Chemistry 274 (53): 38147–38154.

Lobanov AV, Hatfield DL and Gladyshev VN (2008) Reduced reliance on the trace element selenium during evolution of mammals. Genome Biology 9 (3): R62.

López Herráez D, Bauchet M, Tang K, et al. (2009) Genetic variation and recent positive selection in worldwide human populations: evidence from nearly 1 million SNPs. PLoS One 4 (11): e7888.

Mariotti M, Ridge PG, Zhang Y, et al. (2012) Composition and evolution of the vertebrate and mammalian selenoproteomes. PLoS One 7 (3): e33066.

Mertz W (1981) The essential trace elements. Science 213: 1332–1338.

Nazemi L, Nazmara S, Eshraghyan MR, et al. (2012) Selenium status in soil, water and essential crops of Iran. Iranian Journal of Environmental Health Science & Engineering 9 (1): 11.

Ogle RS, Maier KJ, Kiffney P, et al. (1988) Bioaccumulation of selenium in aquatic ecosystems. Lake and Reservoir Management 4 (2): 165–173.

Oldfield JE (2002) Selenium World Atlas. Grimbergen: STDA.

Olds LC and Sibley E (2003) Lactase persistence DNA variant enhances lactase promoter activity in vitro: functional role as a cis regulatory element. Human Molecular Genetics 12 (18): 2333–2340.

Painter EP (1941) The chemistry and toxicity of selenium compounds, with special reference to the selenium problem. Chemical Reviews 28 (2): 179–213.

Rayman MP (2012) Selenium and human health. Lancet 379: 1256–1268.

Romagné F, Santesmasses D, White L, et al. (2014) SelenoDB 2.0: annotation of selenoprotein genes in animals and their genetic diversity in humans. Nucleic Acids Research 42: D437–D443.

Rother Michael (2015) Selenocysteine. In: eLS Chichester: John Wiley & Sons Ltd. DOI: 10.1002/9780470015902.a0000688.pub3

Sager M (2006) Selenium in agriculture, food, and nutrition. Pure and Applied Chemistry 78 (1): 111–133.

Schwarz K and Foltz CM (1957) Selenium as an integral part of factor 3 against dietary necrotic liver degeneration. Journal of the American Chemical Society 79 (12): 3292–3293.

Selinus O, Alloway B, Centeno JA, et al. (2005) Essentials of Medical Geology: Impacts of the Natural Environment on Public Health. Burlington: Elsevier Academic Press.

Shenkin Alan (2001) Trace Element Deficiency. In: eLS Chichester: John Wiley & Sons Ltd.

Snider GW, Ruggles E, Khan N and Hondal RJ (2013) Selenocysteine confers resistance to inactivation by oxidation in thioredoxin reductase: comparison of selenium and sulfur enzymes. Biochemistry 52 (32): 5472–5481.

Stadtman TC (1974) Selenium biochemistry. Science 183 (4128): 915–922.

Stadtman TC (1996) Selenium biochemistry. Annual Review of Biochemistry 65: 83–100.

Stewart R, Grosell M, Buchwalter D, Fisher N, Luoma S, Mathews T, Orr P and Wang W (2010) Bioaccumulation and trophic transfer of selenium. In: Chapman PM (ed) Ecological Assessment of Selenium in the Aquatic Environment, pp. 93–139. Boca Raton, Florida: SETAC in collaboration with CRC Press.

Tishkoff SA, Reed FA, Ranciaro A, et al. (2007) Convergent adaptation of human lactase persistence in Africa and Europe. Nature Genetics 39: 31–40.

Weir BS and Cockerham CC (1984) Estimating F‐statistics for the analysis of population‐structure. Evolution 38: 1358–1370.

White L, Romagné F, Müller E, et al. (2015) Genetic adaptation to levels of dietary selenium in recent human history. Molecular and Biological Evolution 32 (6): 1507–1518.

Wilber CG (1980) Toxicology of selenium: a review. Clinical Toxicology 17 (2): 171–230.

Xia Y, Hill KE, Byrne DW, Xu J and Burk RF (2005) Effectiveness of selenium supplements in a low‐selenium area of China. American Journal of Clinical Nutrition 81: 829–834.

Further Reading

Arner E and Lillig CH (2009) Special issue: selenoprotein expression and function. Biochimica et Biophysica Acta 1790: 1387–1586.

Hatfield DL, Schweizer U, Tsuji PA and Gladyshev VN (eds) (2016) Selenium: Its Molecular Biology and Role in Human Health, 4th edn. New York: Springer.

Innan H and Kondrashov F (2010) The evolution of gene duplications: classifying and distinguishing between models. Nature Reviews Genetics 11: 97–108.

Orr HA (2005) The genetic theory of adaptation: a brief history. Nature Reviews Genetics 6: 119–127.

Pritchard JK, Pickrell JK and Coop G (2010) The genetics of human adaptation: hard sweeps, soft sweeps, and polygenic adaptation. Current Biology 20: R208–R215.

Savolainen O, Lascoux M and Merilä J (2013) Ecological genomics of local adaptation. Nature Reviews Genetics 14: 807–820.

Selinus O and Alloway BJ (eds) (2005) Essentials of Medical Geology: Impacts of the Natural Environment on Public Health. Amsterdam (The Netherlands): Elsevier Academic Press.

Stephan W (2016) Signatures of positive selection: from selective sweeps at individual loci to subtle allele frequency changes in polygenic adaptation. Molecular Ecology 25: 79–88.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
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]