title: Analysis of candidate genes for lineage-specific expression changes in humans and primates.
abstract: RUNX2, a gene involved in skeletal development, has previously been shown to be potentially affected by positive selection during recent human evolution. Here we have used antibody-based proteomics to characterize potential differences in expression patterns of RUNX2 interacting partners during primate evolution. Tissue microarrays consisting of a large set of normal tissues from human and macaque were used for protein profiling of 50 RUNX2 partners with immunohistochemistry. Eleven proteins (AR, CREBBP, EP300, FGF2, HDAC3, JUN, PRKD3, RUNX1, SATB2, TCF3, and YAP1) showed differences in expression between humans and macaques. These proteins were further profiled in tissues from chimpanzee, gorilla, and orangutan, and the corresponding genes were analyzed with regard to genomic features. Moreover, protein expression data were compared with previously obtained RNA sequencing data from six different organs. One gene (TCF3) showed significant expression differences between human and macaque at both the protein and RNA level, with higher expression in a subset of germ cells in human testis compared with macaque. In conclusion, normal tissues from macaque and human showed differences in expression of some RUNX2 partners that could be mapped to various defined cell types. The applied strategy appears advantageous to characterize the consequences of altered genes selected during evolution.
authors.affiliation: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University , Dag Hammarskjölds väg 20, SE-751 85 Uppsala, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Lindskog
authors.forename: Martin
authors.initials: M
authors.lastname: Kuhlwilm
authors.forename: Armaity
authors.initials: A
authors.lastname: Davierwala
authors.forename: Ning
authors.initials: N
authors.lastname: Fu
authors.forename: Geeta
authors.initials: G
authors.lastname: Hegde
authors.forename: Mathias
authors.initials: M
authors.lastname: Uhlén
authors.forename: Sanjay
authors.initials: S
authors.lastname: Navani
authors.forename: Svante
authors.initials: S
authors.lastname: Pääbo
authors.forename: Fredrik
authors.initials: F
authors.lastname: Pontén
mesh_terms: D000818:Animals; D001483:Base Sequence; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism*; D019143:Evolution, Molecular; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D046228:Microarray Analysis / Q000379:methods; D008969:Molecular Sequence Data; D011323:Primates / Q000235:genetics*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D012641:Selection, Genetic; D016415:Sequence Alignment; D017423:Sequence Analysis, RNA; D013045:Species Specificity
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D011506:Proteins; C493709:RUNX2 protein, human