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J G Gilman

Publications and source records attributed to J G Gilman.

47 records · Page 3Linked to original sources
PubMed1979

Evolutionary potential: a mathematical hypothesis of mouse hemoglobin beta chain evolution.

This paper examines the possibility that the linkage arrangements and regulatory properties of genes may be influenced by selection. A mathematical hypothesis is developed in order to show how selective properties of hemoglobin beta chains could have influenced the linkage and regulation of their structural genes. The hypothesis is applied to the case of mouse hemoglobin beta chains. In most mice, closely-linked pairs of loci (doublets) code for two structurally divergent beta chains in unequal amounts. Some mouse strains have singlet alleles, however, coding for another beta chain variant. With the mathematical hypothesis, one can show that selectively determined "evolutionary potentials" may have favored changes in proportions of major and minor chains produced by a doublet allele. In the extreme case, zero production of the minor chain may give a selective advantage, leading to a singlet; conversely, selection may favor linking another gene to the singlet locus to give a doublet. A specific prediction of the model is the stable maintenance under certain conditions of multiple alleles at regulatory loci. The concept of evolutionary potential thus suggests that selection could have influenced the evolution of genotypic fitnesses, in addition to causing changes in gene frequencies as in standard population genetics models

Animals↗
PubMed1978

The oxygen-linked zinc-binding site of human haemoglobin.

Zn2+ is known to increase the 02 affinity of human haemoglobin. Previous data suggested that Zn2+ exerts its effect by directly binding to haemoglobin, rather than by competing with or binding to 2,3-bisphosphoglycerate. It was also shown that there are two 02-linked zinc-binding sites in haemoglobin, and that Zn2+ does not significantly alter haemoglobin co-operativity or the alkaline Bohr effect. The effect of Zn2+ on 02 affinity of haemoglobin can also be observed for other haemoglobins as diverse as those of cow and chicken. This paper presents new data on the haemoglobin-zinc interaction for normal haemoglobin, des-His146beta-haemoglobin and N-ethylsuccinimide-haemoglobin of humans. For normal haemoglobin (0.05 mM in tetramers), at 20 degrees C in buffer containing 0.1 M-Cl-, 02-dissociation-curve experiments showed that the addition of 0.4-0.5 mM-ZnS04 did not change the Bohr effect between pH 6.71 and 7.29. Similar experiments, with "zinc-ion buffers", showed that the value of the Hill coefficient, h, decreased only slightly if the concentration of free Zn2+ was held constant. For N-ethylsuccinimide-haemoglobin, Zn2+ caused less increase in O2 affinity than for normal haemoglobin. These studies, together with data on the equilibrium binding of Zn2+ to oxy-, deoxy- and des-His146beta-haemoglobins, suggest that zinc is chelated in oxyhaemoglobin by at least three amino acids, two of which are histidine-146beta and cysteine-93beta.

Binding Sites↗
PubMed1976

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

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.

Alleles↗
PubMed1976

Mouse haemoglobin Beta chains. Sequence data on embryonic y chain and genetic linkage of the Y-chain locus to the adult beta-chain locus Hbb.

Embryonic haemoglobin y-chain types were determined by starch-gel electrophoresis for inbred Mus musculus strains Sec/ReJ and Au/SsJ (with Hbbs and Hbbp adult beta-chain alleles respectively) and for random-bred HA/ICR (Swiss) mice, which had been selected to be homozygous for the adult Hbbd beta-chain allele. The strain with the Hbbs allele had y1 embryonic beta chain and the strain with the Hbbd allele had y2. The strain with the Hbbp allele also had y2 chain. A breeding study showed that the maximum recombination frequency between the Hbb locus and the y-chain locus is 5.4% at the 95% confidence level. Embryonic y2 chain was sequenced for 39 positions from the N-terminus with an Edman-Begg sequenator. Some tryptic-peptide composition data were obtained on both y1 and y2 chains. No amino acid substitutions between y1 and y2 chains were found in the 40 positions for which there are common data on the two chains. y2 and adult beta chains are different in 12 of the first 21 positions, but show considerable similarity thereafter. It is suggested that homologous but unequal crossing-over between y-chain and adult beta-chain loci could have given rise to the adult beta-chain allele Hbbd, which produces structurally different major and minor beta chains from two closely linked genes.

Alleles↗
PubMed1972

Hemoglobin Beta chain structural variation in mice: evolutionary and functional implications.

The Hbb(d) allele at the hemoglobin beta chain locus of Mus musculus is composed of two linked genes, coding for structurally different beta chains, betadmin and betadmaj. Mus caroli has only one beta chain, which combines structural features of both betadmin and betadmaj and thus may be a Lepore type of beta chain. Sequence data suggest that selection may have been important in the evolution of the mouse beta chains.

Alleles↗
PubMed1968

Fetal hemoglobin variants in mice.

Two strains of mice, DBA and C3H, have a fetal globin polypeptide chain which differs in electrophoretic mobility from the corresponding fetal chain of the C57B1 strain. Mice of the DBA and C3H strains also differ from those of the C57B1 in adult hemoglobin type. Results of backcrossing the (DBA x C57B1) hybrid to the C57B1 suggest that the fetal chain locus and the adult beta-chain locus are closely linked.

Alleles↗