Introns: Phase Compatibility

Abstract

Introns that lie between coding regions of protein‐coding genes may be assigned to three different phase classes, depending on their position relative to the reading frame of the translated protein: phase 0 (located between two codons), phase 1 (splitting codons between the first and second nucleotides) or phase 2 (splitting codons between the second and third nucleotides). In the case of protein‐coding genes with a unique pattern of pre‐messenger ribonucleic acid (mRNA) splicing (and a unique protein product), the 5′ and 3′ splice junctions of an intron always belong to the same phase class (as defined by the unique protein product).

Keywords: intron phase; splice junction; reading frame; exon shuffling; exon skipping; alternative splicing

Figure 1.

Significance of intron phase in exon shuffling. The boxes represent exons (or exon sets); the connecting lines show the introns. The numbers indicate the phase class of the 5′ and 3′ splice junctions of the intron. Note that deletion, insertion and duplication of modules by intronic recombination join the 5′ splice junction of one intron to the 3′ splice junction of another intron. If the module is ‘symmetrical’ (i.e. when the introns at the 5′ and 3′ boundaries of the module are of identical phase) and the recipient also belongs to the same phase class, then the reading frame is not affected (upper part). However, deletion, duplication or insertion of ‘nonsymmetrical’ exons (i.e. the introns at the 5′ and 3′ boundaries of the exon are of different phase) will disrupt the reading frame (lower part). Reprinted from Patthy with permission from Elsevier.

Figure 2.

Evolution of urokinase, tissue plasminogen activator and factor XII by acquisition of class 1–1 modules. The numbers indicate the phase class of the 5′ and 3′ splice junctions of the introns participating in the assembly process. (For the sake of simplicity, introns within domains are not shown.) The phase 1 intron between the signal peptide domain (S) and trypsin‐homologue domain (P) of the ancestral trypsin‐type protease was a suitable recipient for class 1–1 modules. Note that insertions and duplications of class 1–1 growth factor (G), kringle (K), finger (F) and fibronectin type II (FN2) modules divide and duplicate phase 1 introns. Modular assembly thus resulted in gene structures in which all intermodule introns are phase 1.

Figure 3.

Schematic representation of the structures of the genes of some modular proteins assembled from the class 1–1 C‐type lectin module (LN), class 1–1 epidermal growth factor module (G), class 1–1 complement B‐type module (B), class 1–1 immunoglobulin module (Ig), class 1–1 link protein module (LK), class 1–1 follistatin module (FS) and class 1–1 Kunitz‐type inhibitor module (INH). The numbers indicate the position and phase class of the introns. Phase 1 introns found at the boundaries of modules are highlighted in crossed boxes. The solid boxes on the left‐hand side indicate signal peptide domains; vertical bars represent transmembrane domains. The boxes designating the different domains are drawn to scale. Reprinted from Patthy .

Figure 4.

Comparison of the exon–intron structures of the Drosophila and human tolloid genes. The numbers indicate the position and phase class of the introns. Phase 1 introns found at the boundaries of modules are highlighted. The solid boxes on the left‐hand side indicate signal peptide domains. The boxes designating the different domains are drawn to scale. Reprinted from Patthy .

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Further Reading

Patthy L (1985) Evolution of the proteases of blood coagulation and fibrinolysis by assembly from modules. Cell 41: 657–663.

Patthy L (1991) Exons: original building blocks of proteins? BioEssays 13: 187–192.

Patthy L (1996) Evolution of human proteins by exon‐shuffling. In: Jackson M, Strachan T and Dover GA (eds) Human Genome Evolution, Human Molecular Genetics Series, pp. 35–71. Oxford, UK: BIOS Scientific.

Patthy L (2007) Protein Evolution. Oxford, UK: Blackwell Science.

Web Links

Apolipoprotein B (APOB); LocusID: 338. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=338

Apolipoprotein B (APOB); MIM number: 107730. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?107730

Fibroblast growth factor receptor 2 (FGFR2); LocusID: 2263. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=2263

Fibroblast growth factor receptor 2 (FGFR2); MIM number: 176943. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?176943

Low density lipoprotein receptor (LDLR); LocusID: 3949. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=3949

Low density lipoprotein receptor (LDLR); MIM number: 606945. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?606945

Myeloid cell leukemia sequence 1 (MCL1); LocusID: 4170. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=4170

Myeloid cell leukemia sequence 1 (MCL1); MIM number: 159552. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?159552

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How to Cite close
Patthy, László(Mar 2008) Introns: Phase Compatibility. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005083.pub2]