Human Intronless Genes and their Associated Diseases

Abstract

Intronless genes (IGs) are common in single‐celled eukaryotes, whereas in metazoans they comprise only a small percentage of genes. The distribution of human IGs among functional groups is different from the distribution in the whole human genome: IGs mostly encode signal‐transducing molecules, such as G‐protein coupled receptors, which are the largest family within IGs; the second largest group encodes histones. IGs often exhibit tissue‐specific expression, especially in testis and brain. Accordingly, mutations in IGs are predominantly associated with neurological and developmental disorders, as well as several types of cancer. From the evolutionary viewpoint, most IGs are relatively recent and emerged by retroposition. Processing of messenger ribonucleic acids (mRNAs) encoded by natural IGs is independent of splicing, and resembles the processing of some unspliced viral transcripts. In contrast to random RNA sequences, mRNAs encoded by natural IGs are stable and efficiently accumulate in the cytoplasm.

Key Concepts:

  • Human IGs constitute about 3% of the human genome.

  • Human IGs encode mostly signalling molecules and histones.

  • IG‐associated diseases comprise mostly neurological and developmental disorders and some types of cancer.

  • IGs often display tissue‐specific expression, usually in the nervous system and testis.

  • Most human IGs emerged in the process of retroposition.

  • Natural IGs have evolved their own means of processing, independent of splicing.

Keywords: intronless genes; GPCR; signal‐transducing molecules; histones; retroposition; mRNA nuclear export

Figure 1.

Different processing of transcripts encoded by intron‐containing and intronless genes. mRNAs derived from intron‐containing genes are processed in the nucleus, exported to the cytoplasm, and efficiently translated with the help of several specific splicing factors. These mRNAs are prone to nonsense‐mediated decay. By contrast, transcripts of naturally intronless genes are processed independently of splicing and they usually possess cis‐acting sequences that enable them to exploit the TAP‐mediated export pathway. These transcripts are immune to NMD.

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Further Reading

Hill Aubrey E and Sorscher Eric J (2006) The non‐random distribution of intronless human genes across molecular function categories. FEBS Letters 580: 4303–4305.

Jeffares DC, Penkett CJ and Bähler J (2008) Rapidly regulated genes are intron poor. Trends Genetics 24: 375–378.

Sakharkar KR, Sakharkar MK, Culiat CT, Chow VTK and Pervaiz S (2006) Functional and evolutionary analyses on expressed intronless genes in the mouse genome. FEBS Letters 580: 1472–1478.

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Grzybowska, Ewa A(May 2013) Human Intronless Genes and their Associated Diseases. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0025005]