{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T20:43:54Z","timestamp":1783543434994,"version":"3.55.0"},"reference-count":39,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2000,3,1]],"date-time":"2000-03-01T00:00:00Z","timestamp":951868800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["PO1 HL 59312"],"award-info":[{"award-number":["PO1 HL 59312"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2000,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Glucose 6\u2010phosphate dehydrogenase (G6PD) is a cytosolic enzyme encoded by a housekeeping X\u2010linked gene whose main function is to produce NADPH, a key electron donor in the defense against oxidizing agents and in reductive bio\u2010synthetic reactions. Inherited G6PD deficiency is associated with either episodic hemolytic anemia (triggered by fava beans or other agents) or life\u2010long hemolytic anemia. We show here that an evolutionary analysis is a key to understanding the biology of a housekeeping gene. From the alignment of the amino acid (aa) sequence of 52 glucose 6\u2010phosphate dehydrogenase (G6PD) species from 42 different organisms, we found a striking correlation between the aa replacements that cause G6PD deficiency in humans and the sequence conservation of G6PD: two\u2010thirds of such replacements are in highly and moderately conserved (50\u201399%) aa; relatively few are in fully conserved aa (where they might be lethal) or in poorly conserved aa, where presumably they simply would not cause G6PD deficiency. This is consistent with the notion that all human mutants have residual enzyme activity and that null mutations are lethal at some stage of development. Comparing the distribution of mutations in a human housekeeping gene with evolutionary conservation is a useful tool for pinpointing amino acid residues important for the stability or the function of the corresponding protein. In view of the current explosive increase in full genome sequencing projects, this tool will become rapidly available for numerous other genes.\u2014Notaro, N., Afolayan, A., Luzzatto, L. Human mutations in glucose 6\u2010phosphate dehydrogenase reflect evolutionary history.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    14, 485\u2013494 (2000)\n                  <\/jats:p>","DOI":"10.1096\/fasebj.14.3.485","type":"journal-article","created":{"date-parts":[[2018,1,18]],"date-time":"2018-01-18T09:05:51Z","timestamp":1516266351000},"page":"485-494","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Human mutations in glucose 6\u2010phosphate dehydrogenase reflect evolutionary history"],"prefix":"10.1096","volume":"14","author":[{"given":"ROSARIO","family":"NOTARO","sequence":"first","affiliation":[{"name":"Department of Human Genetics Memorial Sloan\u2010Kettering Cancer Center New York NY 10021 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ADEYINKA","family":"AFOLAYAN","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Memorial Sloan\u2010Kettering Cancer Center New York NY 10021 USA"},{"name":"Department of Biochemistry Obafemi Awolowo University Ile\u2010Ife Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LUCIO","family":"LUZZATTO","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Memorial Sloan\u2010Kettering Cancer Center New York NY 10021 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2000,3]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"3367","volume-title":"The Metabolic and Molecular Basis of Inherited Disease","author":"Luzzatto L.","year":"1995"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199101173240306"},{"key":"e_1_2_7_4_1","first-page":"438","article-title":"\u00dcber ein neues Oxydationsferment und sein Absorptionsspektrum","volume":"254","author":"Warburg O.","year":"1932","journal-title":"Biochem. 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