title: Molecular Characterization of Buffalo Haptoglobin: Sequence Based Structural Comparison Indicates Convergent Evolution Between Ruminants and Human.
abstract: Haptoglobin (Hp) protein has high affinity for hemoglobin (Hb) binding during intravascular hemolysis and scavenges the hemoglobin induced free radicals. Earlier reports indicate about uniqueness of Hp molecule in human and cattle, but in other animals, it is not much studied. In this paper, we characterized buffalo Hp molecule and determined its molecular structure, evolutionary importance, and tissue expression. Comparative analysis and predicted domain structure indicated that the buffalo Hp has an internal duplicated region in α-chain only similar to an alternate Hp2 allele in human. This duplicated part encoded for an extra complement control protein CCP domain. Phylogenetic analysis revealed that buffalo and other ruminants were found to group together separated from all other non-ruminants, including human. The key amino acid residues involved in Hp and Hb as well as Hp and macrophage scavenger receptor, CD163 interactions in buffalo, depicted a significant variation in comparison to other non-ruminant species. Constitutive expression of Hp was also confirmed across all the vital tissues of buffalo, for the first time. Results revealed that buffalo Hp is both structurally and functionally conserved, having internal duplication in α-chain similar to human Hp2 and other ruminant species, which might have evolved separately as a convergent evolutionary process. Furthermore, the presence of extra Hp CCP domain possibly in all ruminants may have an effect during dimerization of molecule in these species.
authors.affiliation: a National Bureau of Animal Genetic Resources , Karnal , India.
authors.forename: S K
authors.initials: SK
authors.lastname: Niranjan
authors.affiliation: a National Bureau of Animal Genetic Resources , Karnal , India.|b RIKEN Center for Life Science Technologies , Yokohama , Japan.
authors.forename: S
authors.initials: S
authors.lastname: Goyal
authors.affiliation: a National Bureau of Animal Genetic Resources , Karnal , India.|c Immune Regulation, World Premier International Research Center, Immunology Frontier Research Center (WPI-IFReC) , Osaka University , Osaka Prefecture , Japan.
authors.forename: P K
authors.initials: PK
authors.lastname: Dubey
authors.affiliation: a National Bureau of Animal Genetic Resources , Karnal , India.
authors.forename: V
authors.initials: V
authors.lastname: Vohra
authors.affiliation: a National Bureau of Animal Genetic Resources , Karnal , India.
authors.forename: S
authors.initials: S
authors.lastname: Singh
authors.affiliation: a National Bureau of Animal Genetic Resources , Karnal , India.|d Animal Production and Health Laboratory, Joint FAO-IAEA Division of Nuclear Techniques in Food and Agriculture , International Atomic Energy Agency , Vienna , Austria.
authors.forename: P
authors.initials: P
authors.lastname: Kathiravan
authors.affiliation: a National Bureau of Animal Genetic Resources , Karnal , India.
authors.forename: R S
authors.initials: RS
authors.lastname: Kataria
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002020:Buffaloes / Q000235:genetics*; D006242:Haptoglobins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D006242:Haptoglobins; D012333:RNA, Messenger
keywords: Bubalus bubalis; CCP domain; duplication; haptoglobin; phylogeny