Gamma-crystallin family of the mouse lens: structural and evolutionary relationships.

Abstract

The heterogeneity inherent among r-crystallins of the mouse lens was investigated by sequence analysis of three r-crystallin-specific cDNAs. Comparison of the nucleotide sequence of these cDNAs and one previously reported by us revealed that the four r-cDNAs share 80-90% homology in nucleotide sequence. The entire 3' half of the coding region shows more variability than the 5' half, whereas the greatest variability is observed in the 3' untranslated region where numerous base substitutions, deletions, and insertions seem to have occurred. Alignment of the amino acid sequences of the four mouse y-crystallins according to the known four structural motifs of the major calf y-crystallin, y-II, suggests that all four mouse polypeptides are structurally very similar to calf y-II. However, most of the mouse polypeptides differ from v-II by the absence of one amino acid residue, resulting in a shorter connecting peptide between the two globular domains of the protein. Primary sequence alignment also revealed that the four mouse y-crystallins are most divergent in the third structural motif of the polypeptide. The significance of these differences in terms of the structure and function of the y-crystallins in the mouse lens is discussed.Approximately 90% of the soluble protein of the vertebrate lens consists of a group of structural proteins known as the crystallins (1, 2). In mammals, these lens-specific proteins can be divided into three antigenically distinct classes, a, 3,B and y, each of which comprises several polypeptides of related primary structure. The importance of the structure and function of these polypeptides has long been indicated by the tight developmental regulation of the different crystallin classes and by their differential spatial distribution within the lens (3).At present, little is known about the functional significance of the heterogeneity inherent among the polypeptides of each crystallin class. As a first step towards addressing this question, we have been involved in a study of the structure of the y-crystallins of the mouse. In the mouse lens, up to seven different y-crystallin polypeptides can be identified by two-dimensional gel electrophoresis (4) and a similar number has been reported for several other animal species (5-7). A number of y-crystallin-specific cDNAs have been isolated from a variety of animal species (5, 8-11) and these have been analyzed by DNA sequencing. We (12) and others (13,14) have shown that the y-crystallins of representative gene members of mice and rats are encoded by a family of genes with a similar structure. All of them contain a small 5' exon, encoding three amino acids, followed by two larger exons of approximately equal size that encode the remainder of the "20-kilodalton polypeptide (12-14). There is a precise correspondence between the two major exons of the gene and the two similar structural domains of the polypeptide, suggesting that the y-crystallins may have evolved by exon duplication and subsequent gene amplification (12)(13)(14).The nucl...

Lens-specific promoter activity of a mouse gamma-crystallin gene.

“…Since these two genes encode identical polypeptides, they presumably represent corresponding members of their respective gene families (5,31). However, the two genes are not entirely identical; the first intron shows considerable sequence divergence and the second intron of the rat y3-1 gene is approximately 1.9 kb while that of the mouse y2 gene is only 0.9 kb.…”

“…The recombinant phage clone, XML2, containing the mouse -y2-crystallin gene was isolated from a X47.1 DBA mouse library (25) using the y2-cDNA, pMy2 (5,49) as a hybridizing probe. The phage screening procedures have been described previously (26).…”

“…Using mouse y-cDNAs (5,49), as probes, we isolated several K phage clones from a X47.1 phage DBA/2 mouse genomic library (25). The DNA sequence of one of the mouse y-crystallin genes, y4, has been reported previously (26).…”

Developmental regulation and cell type‐specific expression of the murine γF‐crystallin gene is mediated through a lens‐specific element containing the γF‐1 binding site

“…The y-crystallins of the murine lens comprise a family of closely related polypeptides (Breitman et al, 1984;McAvoy, 1980;McDevitt et al, 1982) encoded by six tightly linked genes located on chromosomes 1 (Skow, 1982;Quinlan et al, 1987). Studies on expression of the y-crystallin genes in mice and rats have established that the different members of this gene family are activated during embryogenesis coincident with lens fiber cell differentiation; however, they are differentially regulated during development resulting in differences in the relative abundance of individual transcripts in different regions of the adult lens (Van Leen et al, 1987;Murer-Orlando et al, 1987;Breitman et al, 1989;Goring et al, 1992).…”

A computer graphics model of frog γ‐crystallin based on the three‐dimensional structure of calf γ‐II crystallin

“…The complete sequences of six rat y-crystallins have been defined from their cDNA and genomic sequences by Schoenmakers et al [6]; these crystallins are called y-l-l, y-l-2, y-2-1, y-2-2, y-3-1 and y-4-1 in which rat y-1-2 appears to be equivalent to bovine y-11. The sequences of murine y-crystallins have been published [7]. The sequences of two human crystallins, y-1-2 and y-2-1 have also been reported [6].…”