A nucleotide sequence in a gene that does not code for the gene product (compare exon). Introns occur principally in eukaryotes, although they have also been found in certain archaea and cyanobacteria and in some viruses. Introns are transcribed into pre-messenger RNA (pre-mRNA) but are subsequently removed from the primary transcript before the mature mRNA transcript moves into the cytoplasm for translation (see rna processing). In certain cases, removal of the introns is an autocatalytic process—self-splicing—whereby the RNA itself has the properties of an enzyme (see ribozyme). Self-splicing occurs in primary transcripts of some single-celled organisms, such as Tetrahymena, as well as chloroplasts, mitochondria, and some viruses. However, splicing of eukaryote primary transcripts produced in the nucleus generally requires the participation of a spliceosome, a complex of proteins and RNAs. In the earliest eukaryotes introns may simply have been sequences of selfish DNA, able to move between different loci within the genome (see transposon) with no benefit to the host. However, they now serve a range of valuable functions in gene expression and DNA organization. Introns act as ‘spacers’ for exons and facilitate alternative splicing to create distinct mRNAs from the same gene. They contain regulatory sequences, such as enhancers and silencers, that control transcription of their ‘host’ gene. Introns contain genes for non-coding RNAs, such as microRNAs and short interfering RNAs, which can suppress translation of the messenger RNA or direct it for degradation. In some cases the transcription of introns may serve as a mechanism to specify the timing between activation of a gene and the appearance of its protein product. Moreover, the placement of introns can influence the way in which chromosomes are packaged into nucleosomes. Of evolutionary significance is exon shuffling—the recombination or rearrangement of exons encoding functional domains of proteins that is permitted by the presence of introns. This permits rapid evolution of proteins with novel permutations of functional groups.