The evolution of an alternatively spliced exon in the alphaA-crystallin gene.
The evolutionary aspects of alternative splicing, as a mechanism to increase the diversity of gene products, are poorly understood. Here we analyse the evolution of a 69-bp exon that is alternatively spliced in the primary transcript of the gene for the mammalian eye lens protein alphaA-crystallin. In rodents, the skipping of this exon 2 is attributed to the presence of a non-consensus 5' splice site GC, and results in the expression of 10-20% of alphaA(ins)-crystallin, with an insert of 23 residues, as compared with normal alphaA-crystallin. alphaA(ins)-crystallin is also expressed in some non-rodent mammals, including kangaroo, while lacking in others. We now demonstrate that the alternatively spliced exon 2 is present in mammals from different orders that do not express alphaA(ins)-crystallin. The expression of this exon has thus been silenced independently in various lineages. Sequence comparison in 16 species reveals that--whether or not alphaA(ins)-crystallin is expressed--exon 2 is always flanked by the non-consensus donor splice site GC, while a consensus branch point sequence and 3' pyrimidine-rich region are hardly detectable in the downstream intron. Increased numbers of amino acid replacements in the peptide encoded by exon 2 indicate that it is subject to much lower selective constraints than the exons that code for normal alphaA-crystallin. The absence of any apparent advantage at the protein level may suggest that exon 2 DNA sequences are conserved as cis-acting factors for proper splicing of the alphaA-crystallin transcript.
van Dijk
M A
MA
161 Department of Biochemistry, University of Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
Sweers
M A
MA
de Jong
W W
WW
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D002417:Cattle; D003459:Crystallins / Q000737:chemistry* / Q000235:genetics*; D019143:Evolution, Molecular; D005091:Exons; D007438:Introns; D007908:Lens, Crystalline / Q000378:metabolism; D008322:Mammals; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D010802:Phylogeny; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
D003459:Crystallins; D010455:Peptides; D012333:RNA, Messenger