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Mouse haemoglobin beta chains. Comparative sequence data on adult major and minor beta chains from two species, Mus musculus and Mus cervicolor.

ABSTRACT: In inbred Mus musculus several different beta chains are known. In certain strains two beta chains are produced in unequal amounts by the two closely linked genes of the doublet breeding unit allele Hbb(d): Betadmaj and betadmin. One strain has a variant doublet allele, Hbb(p), which produces a variant minor beta chain, betapmin (the major beta chain, betapmaj, may not differ from betadmaj chain). Certain other strains have a singlet allele, Hbb(s), that produces only one beta chain, betas. Other species have different beta-chain patterns. In M. cervicolor two variant major beta chains are found, betacmaj (d-like) and betacmaj (s-like), both of which were found associated with minor beta chains. M. caroli has only one, 'Leporelike' beta chain, with structural features characteristic predominantly of betadmin chain in the N-terminal half and of betadmaj chain in the C-terminal half. The present paper presents sequence data on betas, betadmaj, betadmin, betapmin and betacmaj (d-like) chains. The data on betadmin chain cover almost the whole of that chain and show a minimum of nine differences from betadmaj chain and two from betapmin chain. It is suggested that the data on the beta chains of the various species show evidence for the past occurrence of double crossovers over regions within a gene coding for only one or a few amino acids, which events can be explained by the 'hybrid DNA' models of genetic recombination. Supplementary information on the amino acid sequence of the proteins has been deposited as Supplementary Publication SUP 50067 (36 pages) at the British Library Lending Division, Boston Spa, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1976) 153, 5.

SUBMITTER: Gilman JG

PROVIDER: S-EPMC1164036 | biostudies-other | 1976 Oct

REPOSITORIES: biostudies-other

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Project description:BACKGROUND: Due to their high level of genotypic and phenotypic variability, Mus spretus strains were introduced in laboratories to investigate the genetic determinism of complex phenotypes including quantitative trait loci. Mus spretus diverged from Mus musculus around 2.5 million years ago and exhibits on average a single nucleotide polymorphism (SNP) in every 100 base pairs when compared with any of the classical laboratory strains. A genoproteomic approach was used to assess polymorphism of the major milk proteins between SEG/Pas and C57BL/6J, two inbred strains of mice representative of Mus spretus and Mus musculus species, respectively. RESULTS: The milk protein concentration was dramatically reduced in the SEG/Pas strain by comparison with the C57BL/6J strain (34 ± 9 g/L vs. 125 ± 12 g/L, respectively). Nine major proteins were identified in both milks using RP-HPLC, bi-dimensional electrophoresis and MALDI-Tof mass spectrometry. Two caseins (? and ?s1) and the whey acidic protein (WAP), showed distinct chromatographic and electrophoresis behaviours. These differences were partly explained by the occurrence of amino acid substitutions and splicing variants revealed by cDNA sequencing. A total of 34 SNPs were identified in the coding and 3'untranslated regions of the SEG/Pas Csn1s1 (11), Csn2 (7) and Wap (8) genes. In addition, a 3 nucleotide deletion leading to the loss of a serine residue at position 93 was found in the SEG/Pas Wap gene. CONCLUSION: SNP frequencies found in three milk protein-encoding genes between Mus spretus and Mus musculus is twice the values previously reported at the whole genome level. However, the protein structure and post-translational modifications seem not to be affected by SNPs characterized in our study. Splicing mechanisms (cryptic splice site usage, exon skipping, error-prone junction sequence), already identified in casein genes from other species, likely explain the existence of multiple ?s1-casein isoforms both in SEG/Pas and C57BL/6J strains. Finally, we propose a possible mechanism by which the hallmark tandem duplication of a 18-nt exon (14 copies) may have occurred in the mouse genome.

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Mouse haemoglobin beta chains. Comparative sequence data on adult major and minor beta chains from two species, Mus musculus and Mus cervicolor.

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