Splicing may occur so that (1) each and every exon in a pre-mRNA is in-corporated into one mature mRNA through the joining of all successive exons, or (2) one combination of exons in a pre-mRNA is incorporated in one pre-mRNA while other combinations are incorporated in other mRNAs. At present it appears that about 42% of total human transcription units use the latter form of splicing, to produce mRNA. However, this estimate is probably low because the ESTs used to detect alternative splicing come from a limited number of tissues or developmental states, and cover only part of each mRNA. More thorough studies of chromosome 22 show that 59% of its genes are alternatively spliced and even this number may be low.
    Exons are either constitutive or regulated. A constitutive exon is included in all mRNAs formed. A regulated exon, also called a cassette exon, is an exon that is included in some mRNAs and excluded from other mRNAs. Many alternate spiicing patterns are possible for a typical multi-exon pre-mRNA. A cassette exon located between two constitutive exons may either be included or skipped when a pre-mRNA is spliced to form mRNA. Inclusion of one cassette exon may prevent the inclusion of other cassette exons. Mutually exclusive splicing occurs when an array of cassette exons is located between two constitutive exons and only one of the cassette exons can be incorporated into mature mRNA. An intron between two constitutive exons may be included in some mRNAs but not in others. Thus, a single DNA sequence may act as either an intron (when it is excised) or an exon (when it is incorporated). Some exons have alternative splice sites at their 3'-end or their 5'-end. When mRNAs formed by alternative splicing of a given pre-mRNA are translated, the proteins formed usually share common functions but differ within one or more domains. Sometimes, alternative splicing introduces a termination codon in mRNA, causing a premature end to protein synthesis. Alternative splicing may also alter the reading frame so that the same RNA sequence is present in two different reading frames.