Proteins allelic polymorphism

Metallothioneins from Neurospora crassa contain only 25 amino acid residues, but the primary structure is quite similar to the N-terminal part of the mammalian proteins.1454 These data indicate that the gene that codes for the Neurospora crassa metallothionein is evolutionary related to the gene of the vertebrate metallothioneins. Equine metallothionein exists in two major variants (metallothionein 1A and metallothionein 2A), which show remarkable similarities. Some allelic polymorphic variants also occur in man, horse and rabbit. Recent developments have been comprehensively reviewed.14678... 

Allelic polymorphism in a specific gene can produce nearly identical proteins with primary sequences that differ by one or more amino acids. Primary sequence isoforms can be readily separated by CIEF on the basis of their pi if the amino acid substitution changes the surface charge of the protein. Similarly, enzymatic or nonenzymatic posttranslational chemical modification of ionizable protein functional groups can produce chemically distinct isoforms of the same protein with detectably different surface charge and pi. Analysis of hemoglobin by CIEF is an excellent example of how this technique can be applied for the identification and quantification of a family of related proteins that represent a concise subset of the human proteome. Members of this family include many primary... 

Polymorphism A common (i.e., at least 1% prevalence of the minor allele in the population) sequence variation observed in an individual at a polymorphic site. Polymorphisms include nucleotide substitutions, insertions, deletions and microsatellites. They may be functional or silent, i.e., they do not result in detectable differences in gene expression or protein function. 

Electrophoresis remained for several decades the most powerful method for demonstrating polymorphism in human proteins. The striking biochemical individuality of human proteins emerged slowly. Harris (1966) demonstrated the existence of many polymorphisms in 3 of 10 enzymes studied in detail. He found an average heterozygosity (in his case the mean fraction of electrophoretically visible allele differences) of 10% in a sample of ethnic Europeans. Later on he extended the set of enzymes and confirmed the range of frequency values. 

If in a DNA or protein sequence a single position is variant, this may be called a polymorphism or mutation. The difference is set by convention a mutation is rare, and a polymorphism is common. By implication, a mutation may be deleterious, or in rare cases it may be advantageous for the reproductive fitness of its carriers. A widespread polymorphism, on the other hand, is unlikely to affect the fitness to such an extent. A frequency value of 1 % of the polymorphic allele is usually taken as a threshold between mutation and polymorphism (Ki-mura, 1983 Li, 1997). A polymorphic site is called biallelic if two variants segregate in the population, and multiallelic if there are more than two variants, which is a rare event in human sequences. 

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