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Selenium and Genome Annotation (Sergi Castellano)

(Former group hosted by the Department of Evolutionary Genetics)

The group was a member of the Genetics Department from 2010 to 2017 and is moving to University College London.

Much of our work focuses on the identification and characterization of functional elements in eukaryotic genomes, primarily using selenium-dependent genes as our study system. On the one hand, we develop and apply methods to identify and annotate selenoprotein genes, which are usually missannotated in standard databases. On the other, we use population genetics and molecular evolution approaches to study the evolution of the use of selenocysteine, the selenium-containing amino acid, compared to cysteine in proteins. Because nutrition is a prominent selective force in humans and other primates, we are currently working in whether differences in dietary selenium have shaped the use and regulation of selenium and selenoproteins in these species. We are also interested in more theoretical aspects of sequence evolution.

Ongoing projects include:

  • Frédéric Romagné is working on the identification and correct annotation of selenoprotein genes. We have recently released annotations for more than 50 animal genomes for an update of our database of selenoproteins. Elias Mueller is working with Frédéric on this project.
  • Louise White is working on the identification of signatures of local adaptation to levels of dietary selenium in recent human evolution. Selenium in the diet varies widely among human populations and we have addressed this question through the resequencing of selenoprotein genes across populations around the world.
  • Gaurab Sarangi is working on the assessment of the exchangeability between cysteine and selenocysteine, the 21st amino acid in the genetic code, in protein function. In particular, we are interested in the role of compensatory mutations after the loss of selenocysteine in selenoproteins.

Since moving to MPI in 2010, we have also taken an interest in the analysis of ancient genomes. We are particularly interested in contributing to the population genetics analysis of Neandertals. In collaboration with the group of Svante Pääbo, we have recently analyzed the patterns of coding variation in Neandertals. We are also interested in the population history of Neandertals and have recently shown that, in addition to the known interbreeding events 50,000-60,000 years ago, Neandertals interbred with modern humans as early as 100,000 years ago. Despite these multiple interbreeding events, the Neandertal Y lineage is most likely extinct in modern humans.

Finally, we are collaborating with Aida Andrés in a number of projects on primate evolution.

Former staff

  • Sergi Castellano, group leader
  • Eva Erlebach, project student
  • Johanna Hellinger, HiWi student
  • Ron Hübler, master student
  • Iago Maceda-Porto, visiting student
  • Elias Müller, HiWi student
  • Genís Parra, bioinformatician
  • Frédéric Romagné, bioinformatician
  • Gaurab Sarangi, postdoc
  • Joshua Schmidt, postdoc
  • Vladimir Virlan, master student
  • Louise White, PhD student



Schmidt, J., de Manuel, M., Marques-Bonet, T., Castellano, S., & Andrés, A. M. (2019). The impact of genetic adaptation on chimpanzee subspecies differentiation. PLOS Genetics, 15(11), 1-32.
Open Access    DOI    BibTeX   Endnote   


Battlay, P., Leblanc, P. B., Green, L., Garud, N. R., Schmidt, J., Fournier-Level, A., & Robin, C. (2018). Structural variants and selective sweep Foci contribute to insecticide resistance in the Drosophila genetic reference panel. G3: Genes, Genomes, Genetics, 8(11), 3489-3497.
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Key, F. M., Abdul-Aziz, M. A., Mundry, R., Peter, B. M., Sekar, A., D'Amato, M., Dennis, M. Y., Schmidt, J. M., & Andrés, A. M. (2018). Human local adaptation of the TRPM8 cold receptor along a latitudinal cline. PLoS Genetics, 14(5): e1007298.
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Bitarello, B. D., de Filippo, C., Teixeira, J. C., Schmidt, J. M., Kleinert, P., Meyer, D., & Andrés, A. M. (2018). Signatures of long-term balancing selection in human genomes. Genome Biology and Evolution, 10(3), 939-955.
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Schmidt, J. M., Battlay, P., Gledhill-Smith, R. S., Good, R. T., Lumb, C., Fournier-Level, A., & Robin, C. (2017). Insights into DDT resistance from the drosophila melanogaster genetic reference panel. Genetics, 207(3), 1181-1193.
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Martin, M. D., Jay, F., Castellano, S., & Slatkin, M. (2017). Determination of genetic relatedness from low-coverage human genome sequences using pedigree simulations. Molecular Ecology, 26(16), 4145-4157.
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Sarangi, G. K., White, L., & Castellano, S. (2017). Genetic adaptation and Selenium uptake in vertebrates. In Encyclopedia of the Life Sciences. Chichester [u.a.]: Wiley.
DOI    BibTeX   Endnote   


Gladyshev, V. N., Arnér, E. S., Berry, M. J., Brigelius-Flohé, R., Bruford, E. A., Burk, R. F., Carlson, B. A., Castellano, S., Chavatte, L., Conrad, M., Copeland, P. R., Diamond, A. M., Driscoll, D. M., Ferreiro, A., Flohé, L., Green, F. R., Guigó, R., Handy, D. E., Hatfield, D. L., Hesketh, J., Holmgren, A., Hoffmann, P. R., Hondal, R. J., Howard, M. T., Huang, K., Kim, H.-Y., Köhrle, J., Kim, I. Y., Krol, A., Kryukov, G. V., Lee, B. J., Lee, B. C., Lei, X. G., Liu, Q., Lescure, A., Lobanov, A. V., Loscalzo, J., Maiorino, M., Mariotti, M., Prabhu, K. S., Rayman, M. P., Rozovsky, S., Salinas, G., Schmidt, E. E., Schomburg, L., Schweizer, U., Simonovic, M., Sunde, R. A., Tsuji, P. A., Tweedie, S., Ursini, F., Whanger, P. D., & Zhang, Y. (2016). Selenoprotein Gene Nomenclature. The Journal of Biological Chemistry, 291(46), 24036-24040.
DOI    BibTeX   Endnote   

de Manuel, M., Kuhlwilm, M., Frandsen, P., Sousa, V. C., Desai, T., Prado-Martinez, J., Hernandez-Rodriguez, J., Dupanloup, I., Lao, O., Hallast, P., Schmidt, J. M., Heredia-Genestar, J. M., Benazzo, A., Barbujani, G., Peter, B. M., Kuderna, L. F. K., Casals, F., Angedakin, S., Arandjelovic, M., Boesch, C., Kühl, H. S., Vigilant, L., Langergraber, K., Novembre, J., Gut, M., Gut, I., Navarro, A., Carlsen, F., Andrés, A. M., Siegismund, H. R., Scally, A., Excoffier, L., Tyler-Smith, C., Castellano, S., Xue, Y., Hvilsom, C., & Marques-Bonet, T. (2016). Chimpanzee genomic diversity reveals ancient admixture with bonobos. Science, 354(6311), 477-481.
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Fournier-Level, A., Neumann-Mondlak, A., Good, R., Green, L., Schmidt, J. M., & Robin, C. (2016). Behavioural response to combined insecticide and temperature stress in natural populations of Drosophila melanogaster. Journal of Evolutionary Biology, 29(5), 1030-1044.
DOI    BibTeX   Endnote   

Mendez, F. L., Poznik, G. D., Castellano, S., & Bustamante, C. D. (2016). The divergence of Neandertal and modern human Y chromosomes. The American Journal of Human Genetics, 98(4), 728-734.
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Kuhlwilm, M., Gronau, I., Hubisz, M. J., de Filippo, C., Prado-Martinez, J., Kircher, M., Fu, Q., Burbano, H. A., Lalueza-Fox, C., de la Rasilla, M., Rosas, A., Rudan, P., Brajkovic, D., Kucan, Ž., Gušic, I., Marques-Bonet, T., Andrés, A. M., Viola, B., Pääbo, S., Meyer, M., Siepel, A., & Castellano, S. (2016). Ancient gene flow from early modern humans into Eastern Neanderthals. Nature, 530(7591), 429-433.
DOI    BibTeX   Endnote   

White, L., & Castellano, S. (2016). The role of selenium in human evolution. In D. Hatfield, & V. Gladyshev (Eds.), Selenium: Its molecular biology and role in human health (4th ed., pp. 59-71). New York [u.a.]: Springer.
DOI    BibTeX   Endnote   

White, L., & Castellano, S.(2016). Genetische Anpassung an den Selengehalt von Nahrung in der jüngsten Menschheitsgeschichte.
Open Access    DOI    BibTeX   Endnote   


White, L. (2015). Population genetics of selenium-related genes in humans. PhD Thesis, Univ., Leipzig.
BibTeX   Endnote   

White, L., Romagné, F., Müller, E., Erlebach, E., Weihmann, A., Parra, G., Andrés, A. M., & Castellano, S. (2015). Genetic adaptation to levels of dietary selenium in recent human history. Molecular Biology and Evolution, 32(6), 1507-1518.
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Romagné, F., Santesmasses, D., White, L., Sarangi, G. K., Mariotti, M., Hübler, R., Weihmann, A., Parra, G., Gladyshev, V. N., Guigó, R., & Castellano, S. (2014). SelenoDB 2.0: Annotation of selenoprotein genes in animals and their genetic diversity in humans. Nucleic Acids Research, 42(D1), D437-D443.
Open Access    DOI    BibTeX   Endnote   

Lazaridis, I., Patterson, N., Mittnik, A., Renaud, G., Mallick, S., Kirsanow, K., Sudmant, P. H., Schraiber, J. G., Castellano, S., Lipson, M., Berger, B., Economou, C., Bollongino, R., Fu, Q., Bos, K. I., Nordenfelt, S., Li, H., de Filippo, C., Prüfer, K., Sawyer, S., Posth, C., Haak, W., Hallgren, F., Fornander, E., Rohland, N., Delsate, D., Francken, M., Guinet, J.-M., Wahl, J., Ayodo, G., Babiker, H. A., Bailliet, G., Balanovska, E., Balanovsky, O., Barrantes, R., Bedoya, G., Ben-Ami, H., Bene, J., Berrada, F., Bravi, C. M., Brisighelli, F., Busby, G. B. J., Cali, F., Churnosov, M., Cole, D. E. C., Corach, D., Damba, L., van Driem, G., Dryomov, S., Dugoujon, J.-M., Fedorova, S. A., Romero, I. G., Gubina, M., Hammer, M., Henn, B. M., Hervig, T., Hodoglugil, U., Jha, A. R., Karachanak-Yankova, S., Khusainova, R., Khusnutdinova, E., Kittles, R., Kivisild, T., Klitz, W., Kucinskas, V., Kushniarevich, A., Laredj, L., Litvinov, S., Loukidis, T., Mahley, R. W., Melegh, B., Metspalu, E., Molina, J., Mountain, J., Näkkäläjärvi, K., Nesheva, D., Nyambo, T., Osipova, L., Parik, J., Platonov, F., Posukh, O., Romano, V., Rothhammer, F., Rudan, I., Ruizbakiev, R., Sahakyan, H., Sajantila, A., Salas, A., Starikovskaya, E. B., Tarekegn, A., Toncheva, D., Turdikulova, S., Uktveryte, I., Utevska, O., Vasquez, R., Villena, M., Voevoda, M., Winkler, C. A., Yepiskoposyan, L., Zalloua, P., Zemunik, T., Cooper, A., Capelli, C., Thomas, M. G., Ruiz-Linares, A., Tishkoff, S. A., Singh, L., Thangaraj, K., Villems, R., Comas, D., Sukernik, R., Metspalu, M., Meyer, M., Eichler, E. E., Burger, J., Slatkin, M., Pääbo, S., Kelso, J., Reich, D., & Krause, J. (2014). Ancient human genomes suggest three ancestral populations for present-day Europeans. Nature, 513(7518), 409-413.
DOI    BibTeX   Endnote   

Castellano, S., Parra, G., Sánchez-Quinto, F. A., Racimo, F., Kuhlwilm, M., Kircher, M., Sawyer, S., Fu, Q., Heinze, A., Nickel, B., Dabney, J., Siebauer, M. F., White, L., Burbano, H. A., Renaud, G., Stenzel, U., Lalueza-Fox, C., de la Rasilla, M., Rosas, A., Rudan, P., Brajkovic, D., Kucan, Ž., Gušic, I., Shunkov, M. V., Derevianko, A. P., Viola, B., Meyer, M., Kelso, J., Andrés, A. M., & Pääbo, S. (2014). Patterns of coding variation in the complete exomes of three Neandertals. Proceedings of the National Academy of Sciences of the United States of America, 111(18), 6666-6671.
DOI    PubMed    BibTeX   Endnote   

Hajdinjak, M., Korlević, P., Gansauge, M.-T., Dabney, J., Slon, V., Glocke, I., Sawyer, S., Nickel, B., Nagel, S., Gerber, T., Hopfe, C., Stenzel, U., Renaud, G., Andrés, A. M., Castellano, S., Kelso, J., Prüfer, K., Meyer, M., & Pääbo, S. (2014). Neandertal genetic diversity. Poster presented at XVII World UISPP Congress, Burgos, Spain.
BibTeX   Endnote   


Fu, Q., Mittnik, A., Johnson, P. L., Bos, K., Lari, M., Bollongino, R., Sun, C., Giemsch, L., Schmitz, R., Burger, J., Ronchitelli, A. M., Martini, F., Cremonesi, R. G., Svoboda, J., Bauer, P., Caramelli, D., Castellano, S., Reich, D., Pääbo, S., & Krause, J. (2013). A revised timescale for human evolution based on ancient mitochondrial genomes. Current Biology, 23(7), 553-559.
Open Access    DOI    BibTeX   Endnote   


White, L., & Castellano, S. (2012). Evolutionary basis for the use of selenocysteine. In D. L. Hatfield, M. J. Berry, & V. N. Gladyshev (Eds.), Selenium: Its Molecular Biology and Role in Human Health (3, pp. 85-93). New York [u.a.]: Springer.
DOI    BibTeX   Endnote   


Castellano, S. (2009). On the unique function of selenocysteine - insights from the evolution of selenoproteins. Biochimica et Biophysica Acta, 1790, 1463-1470.

S Castellano*, AM Andrés*, E Bosch, M Bayes, R Guigó and AG Clark (2009). Low exchangeability of selenocysteine, the 21st amino acid, in vertebrate proteins. Molecular Biology and Evolution, 26, 2031-2040 


Castellano, S., Gladyshev, V. N., Guigó, R., & Berry, M. J. (2008). SelenoDB 1.0: A database of selenoprotein genes, proteins and SECIS elements. Nucleic Acids Research, 36(Suppl. 1), D332-D338.
DOI   Database


Castellano, S. (2006). Little biological and statistical support for hundreds of selenoproteins in mouse pseudo-messenger RNAs [A critical assessment of PLoS Genetics, 2, e3 (2006)]. PLoS Genetics.


Castellano, S., Lobanov, A. V., Chapple, C., Novoselov, S. V., Albrecht, M., Hua, D., Lescure, A., Lengauer, T., Krol, A., Gladyshev, V. N., & Guigó, R. (2005). Diversity and functional plasticity of eukaryotic selenoproteins: Identification and characterization of the SelJ family. Proceedings of the National Academy of Sciences of the United States of America, 102(45), 16188-16193.
DOI  Commentary in PNAS

Taskov, K., Chapple, C., Kryukov, G. V., Castellano, S., Lobanov, A. V., Korotkov, K. V., Guigó, R., & Gladyshev, V. N. (2005). Nematode selenoproteome: The use of the selenocysteine insertion system to decode one codon in an animal genome? Nucleic Acids Research, 33(7), 2227-2238.


International Chicken Genome Sequencing Consortium, & Castellano, S. (2004). Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution. Nature, 432, 695-716.
DOI   Commentary in Nature

Jaillon, O., Aury, J.-M., Brunet, F., Petit, J.-L., Stange-Thomann, N., Mauceli, E., Bouneau, L., Fischer, C., Ozouf-Costaz, C., Bernot, A., Nicaud, S., Jaffe, D., Fisher, S., Lutfalla, G., Dossat, C., Segurens, B., Dasilva, C., Salanoubat, M., Levy, M., Boudet, N., Castellano, S., Anthouard, V., Jubin, C., Castelli, V., Katinka, M., Vacherie, B., Biémont, C., Skalli, Z., Cattolico, L., Poulain, J., de Berardinis, V., Cruaud, C., Duprat, S., Brottier, P., Coutanceau, J.-P., Gouzy, J., Parra, G., Lardier, G., Chapple, C., McKernan, K. J., McEwan, P., Bosak, S., Kellis, M., Volff, J.-N., Guigó, R., Zody, M. C., Mesirov, J., Lindblad-Toh, K., Birren, B., Nusbaum, C., Kahn, D., Robinson-Rechavi, M., Laudet, V., Schachter, V., Quétier, F., Saurin, W., Scarpelli, C., Wincker, P., Lander, E. S., & Crollius, J. W. H. R. (2004). Genome duplication in the teleost fish Tetraodon nigroviridis reveals the early vertebrate proto-karyotype. Nature, 431, 946-957.
DOI   Commentary in Nature

Castellano Hereza, S. (2004). Towards the characterization of the eukaryotic selenoproteome: A computational approach. PhD Thesis, Univ. Pompeu Fabra, Barcelona.

Castellano, S., Novoselov, S. V., Kryukov, G. V., Lescure, A., Blanco, E., Krol, A., Gladyshev, V. N., & Guigó, R. (2004). Reconsidering the evolution of eukaryotic selenoproteins: A novel nonmammalian family with scattered phylogenetic distribution. EMBO Reports, 5(1), 71-77.
DOI   Datasets   Commentary in EMBO


Kryukov, G. V., Castellano, S., Novoselov, S. V., Lobanov, A. V., Zehtab, O., Guigó, R., & Gladyshev, V. N. (2003). Characterization of mammalian selenoproteomes. Science, 300(5624), 1439-1443.
DOI   Datasets


Castellano, S., Morozova, N., Morey, M., Berry, M. J., Serras, F., Corominas, M., & Guigó, R. (2001). In silico identification of novel selenoproteins in the Drosophila melanogaster genome. EMBO Reports, 2(8), 697-702.
DOI  Datasets

* Equal contribution