Summary
The exon structure of the collagen IV gene provides a striking example for collagen evolution and the role of introns in gene evolution. Collagen IV, a major component of basement membranes, differs from the fibrillar collagens in that it contains numerous interruptions in the triple helical Gly-X-Y repeat domain. We have characterized all 47 exons in the mouse α2(IV) collagen gene and find two 36-, two 45-, and one 54-bp exons as well as one 99- and three 108-bp exons encoding the Gly-X-Y repeat sequence. All these exon sizes are also found in the fibrillar collagen genes. Strikingly, of the 24 interruption sequences present in the α2-chain of mouse collagen IV, 11 are encoded at the exon/intron borders of the gene, part of one interruption sequence is encoded by an exon of its own, and the remaining interruptions are encoded within the body of exons. In such “fusion exons” the Gly-X-Y encoding domain is also derived from 36-, 45-, or 54-bp sequence elements. These data support the idea that collagen IV genes evolved from a primordial 54-bp coding unit. We furthermore interpret these data to suggest that the interruption sequences in collagen IV may have evolved from introns, presumably by inactivation of splice site signals, following which intronic sequences could have been recruited into exons. We speculate that this mechanism could provide a role for introns in gene evolution in general.
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References
Biggin MD, Gibson TJ, Hong GR (1983) Buffer gradient gels and35S label as an aid to rapid DNA sequence determination. Proc Natl Acad Sci USA 80:3963–3965
Blumberg B, MacKrell AJ, Fessler JH (1988)Drosophila basement membrane procollagen α1(IV). J Biol Chem 263:18328–18337
Boyd C, Byers P, Sundell L (eds) (1990) Biology of extracellular matrix. Academic Press, New York (in press)
Brazel D, Oberbaumer I, Dieringer H, Babel W, Glanville RW, Deutzman R, Kuhn K (1987) Completion of the amino acid sequence of the α1-chain of human basement membrane collagen type IV reveals 21 non-triplet interruptions located within the collagenous domain. Eur J Biochem 168:529–536
Brazel D, Pollner R, Oberbaumer I, Kuhn K (1988) Human basement membrane collagen (type IV). Eur J Biochem 172: 35–42
Burbelo P, Martin G, Yamada Y (1988) α1(IV) and α2(IV) collagen genes are regulated by a bidirectional promoter and a shared enhancer. Proc Natl Acad Sci USA 85:9679–9682
Chu M-L, de Wet W, Bernard M, Ding J-F, Morabito M, Myers J, Williams C, Ramirez F (1984) Human pro 1(I) collagen gene structure reveals evolutionary conservation of a pattern of introns and exons. Nature 310:337–340
Cox G, Fields C, Kramer J, Rosenzweig B, Hirsh D (1989) Sequence comparisons of developmentally regulated collagen genes ofCaenorhabditis elegans. Gene 76:331–344
Craik CS, Sprang S, Fletterick R, Rutter WJ (1982) Intronexon splice junctions map at protein surfaces. Nature 299:180–182
Craik CS, Rutter WJ, Fletterick R (1983) Splice junctions: association with variations in protein structure. Science 220:1125–1129
D'Alessio M, Ramirez F, Suzuki I, Solursh M, Gambino R (1989) Structure and developmental expression of sea urchin fibrillar collagen gene. Proc Natl Acad Sci USA 86:9303–9307
den Dunnen JT, Moorman RJM, Lubsen NH, Schoenmakers JGG (1986) Intron insertions and deletions in the β/γ-crystallin gene. Proc Natl Acad Sci USA 83:2855–2859
Dolz R, Engel J, Kuhn K (1988) Folding of collagen IV. Eur J Biochem 178:357–365
Fields C (1988) Domain organization and intron position inCaenorhabditis elegans collagen genes. The 54-bp module hypothesis revisited. J Mol Evol 28:55–63
Guo X, Kramer JM (1989) The twoC. elegans basement membrane (type IV) collagen genes are located on spearate chromosomes. J Biol Chem 264:17574–17582
Hofman H, Voss T, Kuhn K, Engel J (1984) Localization of flexible sites in thread-like molecules from electron micrographs. Comparison of interstitial, basement membranes and intima collagens. J Mol Biol 172:325–343
Hostikka SL, Tryggvason K (1988) The complete primary structure of the α2 chain of human type IV collagen and comparison with the α1(IV) chain. J Biol Chem 263:19488–19493
Jaworski CJ, Piatigorsky J (1989) A pseudo-exon in the functional human αA-crystallin gene. Nature 337:752–754
Kaytes PJ, Wood L, Theriault N, Kurkinen M, Vogeli G (1988) Head-to-head arrangement of murine type IV collagen genes. J Biol Chem 263:19274–19277
Kramer JM, Cox GN, Hirsch D (1982) Comparisons of the completed sequences of two collagen genes fromCaenorhabditis elegans. Cell 30:599–606
Kurkinen M, Bernard MP, Barlow DP, Chow LT (1985) Characterization of 64, 123, and 182 base pair exons in the mouse α2(IV) collagen gene. Nature 217:177–179
Lim HM, Pene JJ (1988) Optimal conditions for supercoil DNA sequencing with theEscherichia coli DNA polymerase. Gene Technol 5:32–39
Lozano G, Ninomiya Y, Thompson H, Olsen BR (1985) A distinct class of vertebrate collagen genes encodes chicken type IX collagen polypeptides. Proc Natl Acad Sci USA 82:4050–4054
Muthukumaran G, Blumberg B, Kurkinen M (1989) The complete primary structure for the α1-chain of mouse collagen IV. Differential evolution of collagen IV domains. J Biol Chem 264:6310–6317
Nath P, Laurent M, Horn E, Sobel ME, Zon G, Vogeli G (1986) Isolation of an α1 type IV collagen cDNA clone using a synthetic oligodeoxynucleotide. Gene 43:301–304
Ninomiya Y, Gordon M, van der Rest M, Schmid T, Linsenmayer T, Olsen BR (1986) The developmentally regulated type X collagen gene contains a long open reading frame without introns. J Biol Chem 261:5041–5050
Odermatt E, Tamkun JW, Hynes RO (1985) Repeating molecular structure of the fibronectin gene: relationship to protein structure and subunit variation. Proc Natl Acad Sci USA 82:6571–6575
Parma J, Christopher D, Pohl V, Vassart G (1987) Structural organization of the 5′ region of the thyroglobulin gene. Evidence for intron loss and “exonization” during evolution. J Mol Biol 196:769–779
Poschl E, Pollner R, Kuhn K (1988) The genes for the α1(IV) and α2(IV) chains of human basement membrane collagen type IV are arranged head-to-head and separated by a bidirectional promoter of unique structure. EMBO J 7:2687–2695
Runnegar B (1985) Collagen gene construction and evolution. J Mol Evol 22:141–149
Saitta B, Buttice G, Gambina R (1989) Isolation of a putative collagen-like gene from the sea urchinParacentrotus lividus. Biochem Biophys Res Commun 158:633–639
Sakurai Y, Sullivan M, Yamada Y (1986) α1 type IV collagen gene evolved differently from fibrillar collagen genes. J Biol Chem 261:6654–6657
Sanger F, Nicklen S, Coulson AR (1977) DNA sequencing with chain terminating inhibitors. Proc Natl Acad Sci USA 74:5463–5467
Saus J, Quinones S, MacKrell AJ, Blumberg B, Muthukumaran G, Pihlajaniemi T, Kurkinen M (1989) The complete primary structure of mouse α2(IV) collagen. Alignment with mouse α1(IV) collagen. J Biol Chem 264:6318–6324
Soininen R, Tikka L, Chow L, Pihlajaniemi T, Kurkinen M, Prockop DJ, Boyd CD, Tryggvason K (1986) Large introns in the 3′ end of the gene for the proα1(IV) chain of human basement membrane collagen. Proc Natl Acad Sci USA 83:1568–1572
Soininen R, Haka-Risku T, Prockop DJ, Tryggvason K (1987) Complete primary structure of the 1 chain of human basement membrane (type IV) collagen. FEBS Lett 225:188–194
Soininen R, Huotari M, Hostikka SL, Prockop DJ, Tryggvason K (1988) The structural genes for α1 and α2 chains of human type IV collagen are divergently encoded on opposite DNA strands and have an overlapping promoter region. J Biol Chem 263:17217–17220
Solomon E, Hiorns LR, Spurr N, Kurkinen M, Barlow D, Hogan BLM, Dalgleish R (1985) Chromosomal assignments of the genes coding for human types II, III, and IV collagen: a dispersed gene family. Proc Natl Acad Sci USA 82:3330–3334.
Strauss EC, Kobori JA, Sin G, Hood LE (1986) Specific-primerdirected DNA sequencing. Anal Biochem 154:353–360
Tabor S, Richardson CC (1987) DNA sequence analysis with a modified bacteriophage T7 DNA polymerase. Proc Natl Acad Sci USA 84:4767–4771
Timpl R, Dziadek M (1986) Structure, development, and molecular pathology of basement membranes. Int Rev Exp Pathol 29:1–113
Venkatesan M, de Pablo F, Vogeli G, Simpson RT (1986) Structure and developmentally regulated expression of aStrongylocentrotus purpuratus collagen gene. Proc Natl Acad Sci USA 83:3351–3355
Wood L, Theriault N, Vogeli G (1988) cDNA clones completing the nucleotide and derived amino acid sequence of the α1 chain of basement membrane (type IV) collagen from mouse. FEBS Lett 227:5–8
Yamada Y, Avvedimento VE, Mudryj M, Ohkubo H, Vogeli G, Irani M, Pastan I, de Crombrugghe B (1980) The collagen gene: evidence of its evolutionary assembly by amplification of a DNA segment containing an exon of 54 bp. Cell 22:887–893
Yamada Y, Liau G, Mudryj M, Obici S, de Crombrugghe B (1984) Conservation of sizes for one but not another class of exons in two chick collagen genes. Nature 310:333–337
Soininen R, Huotari M, Ganguly A, Prockop DJ, Tryggvason K (1989) Structural organization of the gene for the α1 chain of human type IV collagen. J Biol Chem 264:13565–13571
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Butticè, G., Kaytes, P., D'Armiento, J. et al. Evolution of collagen IV genes from a 54-base pair exon: A role for introns in gene evolution. J Mol Evol 30, 479–488 (1990). https://doi.org/10.1007/BF02101102
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DOI: https://doi.org/10.1007/BF02101102