title: Lineage-Specific Changes in Biomarkers in Great Apes and Humans.
abstract: Although human biomedical and physiological information is readily available, such information for great apes is limited. We analyzed clinical chemical biomarkers in serum samples from 277 wild- and captive-born great apes and from 312 healthy human volunteers as well as from 20 rhesus macaques. For each individual, we determined a maximum of 33 markers of heart, liver, kidney, thyroid and pancreas function, hemoglobin and lipid metabolism and one marker of inflammation. We identified biomarkers that show differences between humans and the great apes in their average level or activity. Using the rhesus macaques as an outgroup, we identified human-specific differences in the levels of bilirubin, cholinesterase and lactate dehydrogenase, and bonobo-specific differences in the level of apolipoprotein A-I. For the remaining twenty-nine biomarkers there was no evidence for lineage-specific differences. In fact, we find that many biomarkers show differences between individuals of the same species in different environments. Of the four lineage-specific biomarkers, only bilirubin showed no differences between wild- and captive-born great apes. We show that the major factor explaining the human-specific difference in bilirubin levels may be genetic. There are human-specific changes in the sequence of the promoter and the protein-coding sequence of uridine diphosphoglucuronosyltransferase 1 (UGT1A1), the enzyme that transforms bilirubin and toxic plant compounds into water-soluble, excretable metabolites. Experimental evidence that UGT1A1 is down-regulated in the human liver suggests that changes in the promoter may be responsible for the human-specific increase in bilirubin. We speculate that since cooking reduces toxic plant compounds, consumption of cooked foods, which is specific to humans, may have resulted in relaxed constraint on UGT1A1 which has in turn led to higher serum levels of bilirubin in humans.
authors.affiliation: Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig, Germany.
authors.forename: Claudius
authors.initials: C
authors.lastname: Ronke
authors.affiliation: Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Dannemann
authors.affiliation: Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
authors.forename: Michel
authors.initials: M
authors.lastname: Halbwax
authors.affiliation: Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Fischer
authors.affiliation: Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig, Germany.
authors.forename: Christin
authors.initials: C
authors.lastname: Helmschrodt
authors.affiliation: Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Brügel
authors.affiliation: Lola Ya Bonobo Sanctuary, "Petites Chutes de la Lukaya," Kinshasa, Democratic Republic of Congo.
authors.forename: Claudine
authors.initials: C
authors.lastname: André
authors.affiliation: Réserve Naturelle Sanctuaire à Chimpanzés de Tchimpounga, Jane Goodall Institute, Pointe-Noire, Republic of Congo.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Atencia
authors.affiliation: Conservation & Ecosystem Health Alliance (CEHA), Kampala, Uganda; College of Veterinary Medicine, Animal Resources & Biosecurity, Makerere University, Kampala, Uganda.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Mugisha
authors.affiliation: Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Scholz
authors.affiliation: Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Ceglarek
authors.affiliation: Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Thiery
authors.affiliation: Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
authors.forename: Svante
authors.initials: S
authors.lastname: Pääbo
authors.affiliation: Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
authors.forename: Kay
authors.initials: K
authors.lastname: Prüfer
authors.affiliation: Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
authors.forename: Janet
authors.initials: J
authors.lastname: Kelso
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D002802:Cholinesterases / Q000097:blood; D015536:Down-Regulation; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D015186:Hominidae / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000378:metabolism; D008253:Macaca mulatta / Q000097:blood / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D013045:Species Specificity; D055815:Young Adult; D000099148:UGT1A1 Enzyme
chemical_list: D016632:Apolipoprotein A-I; D001663:Bilirubin; D015415:Biomarkers; D002802:Cholinesterases; D014453:Glucuronosyltransferase; D007770:L-Lactate Dehydrogenase; D012333:RNA, Messenger; D000099148:UGT1A1 Enzyme