Intergenic region

An Intergenic region (IGR) is a stretch of DNA sequences located between genes.[1] Intergenic regions are a subset of noncoding DNA. Occasionally some intergenic DNA acts to control genes nearby, but most of it has no currently known function. It is one of the DNA sequences sometimes referred to as junk DNA, though it is only one phenomenon labeled such and in scientific studies today, the term is less used. Recently transcribed RNA from the DNA fragments in intergenic regions were known as "dark matter" or "dark matter transcripts".[2]

Illustration of intergenic DNA

Properties

Intergenic regions are different from intragenic regions (or introns), which are short, non-coding regions that are found within genes, especially within the genes of eukaryotic organisms.

According to the ENCODE project's study of the human genome, due to "both the expansion of genic regions by the discovery of new isoforms and the identification of novel intergenic transcripts, there has been a marked increase in the number of intergenic regions (from 32,481 to 60,250) due to their fragmentation and a decrease in their lengths (from 14,170 bp to 3,949 bp median length)"[3]

Scientists have now artificially synthesized proteins from intergenic regions.[4]

Functions

Historically intergenic regions have sometimes been called junk DNA suggesting that they have no function. However, it has been known for a long time that these regions do contain functionally important elements such as promoters and enhancers. In particular, intergenic regions often contain enhancer DNA sequences, which can activate expression of discrete sets of genes over distances of several thousand base pairs. Changes in the proteins bound on enhancers reprogram gene expression and affect the cell phenotype. [5] [6] Also intergenic regions may contain as yet unidentified genes such as noncoding RNAs. Though little is known about them, they are thought to have regulatory functions. In recent years the ENCODE project has been studying intergenic regions in humans in more detail.[7][8] Statistical method has been specifically developed to detect trait- or disease-associated regions located in intergenic region using whole genome sequencing data, including sliding window procedure[9] and dynamic window procedure.[10][11]

Intergenic regions in organisms

In humans, intergenic regions comprise about 50% of the genome, whereas this number is much less in bacteria (15%) and yeast (30%) [12]

In Plasmodium falciparum, many intergenic regions have an AT content of 90% [13]

See also

References
  1. Tropp BE (2008). Molecular Biology: Genes to Proteins. Jones & Bartlett Learning. ISBN 9780763709167.
  2. van Bakel H, Nislow C, Blencowe BJ, Hughes TR (May 2010). "Most "dark matter" transcripts are associated with known genes". PLOS Biology. 8 (5): e1000371. doi:10.1371/journal.pbio.1000371. PMC 2872640. PMID 20502517.
  3. Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T, Mortazavi A, et al. (September 2012). "Landscape of transcription in human cells". Nature. 489 (7414): 101–8. Bibcode:2012Natur.489..101D. doi:10.1038/nature11233. PMC 3684276. PMID 22955620.
  4. Dhar PK, Thwin CS, Tun K, Tsumoto Y, Maurer-Stroh S, Eisenhaber F, Surana U (February 2009). "Synthesizing non-natural parts from natural genomic template". Journal of Biological Engineering. 3: 2. doi:10.1186/1754-1611-3-2. PMC 2642765. PMID 19187561.
  5. Schmidt SF, Larsen BD, Loft A, Nielsen R, Madsen JG, Mandrup S (September 2015). "Acute TNF-induced repression of cell identity genes is mediated by NFκB-directed redistribution of cofactors from super-enhancers". Genome Research. 25 (9): 1281–94. doi:10.1101/gr.188300.114. PMC 4561488. PMID 26113076.
  6. Vlahopoulos SA (August 2017). "Aberrant control of NF-κB in cancer permits transcriptional and phenotypic plasticity, to curtail dependence on host tissue: molecular mode". Cancer Biology & Medicine. 14 (3): 254–270. doi:10.20892/j.issn.2095-3941.2017.0029. PMC 5570602. PMID 28884042.
  7. Birney E, Stamatoyannopoulos JA, Dutta A, Guigó R, Gingeras TR, Margulies EH, et al. (June 2007). "Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project". Nature. 447 (7146): 799–816. Bibcode:2007Natur.447..799B. doi:10.1038/nature05874. PMC 2212820. PMID 17571346.
  8. Dunham I (September 2012). "An integrated encyclopedia of DNA elements in the human genome". Nature. 489 (7414): 57–74. Bibcode:2012Natur.489...57T. doi:10.1038/nature11247. PMC 3439153. PMID 22955616.
  9. Morrison AC, Huang Z, Yu B, Metcalf G, Liu X, Ballantyne C, et al. (February 2017). "Practical Approaches for Whole-Genome Sequence Analysis of Heart- and Blood-Related Traits". American Journal of Human Genetics. 100 (2): 205–215. doi:10.1016/j.ajhg.2016.12.009. PMC 5294677. PMID 28089252.
  10. Li Z, Li X, Liu Y, Shen J, Chen H, Zhou H, et al. (May 2019). "Dynamic Scan Procedure for Detecting Rare-Variant Association Regions in Whole-Genome Sequencing Studies". American Journal of Human Genetics. 104 (5): 802–814. doi:10.1016/j.ajhg.2019.03.002. PMC 6507043. PMID 30982610.
  11. Li, Zilin; Liu, Yaowu; Lin, Xihong (2020-09-14). "Simultaneous Detection of Signal Regions Using Quadratic Scan Statistics With Applications to Whole Genome Association Studies". Journal of the American Statistical Association: 1–30. arXiv:1710.05021. doi:10.1080/01621459.2020.1822849. ISSN 0162-1459.
  12. Francis WR, Wörheide G (June 2017). "Similar Ratios of Introns to Intergenic Sequence across Animal Genomes". Genome Biology and Evolution. 9 (6): 1582–1598. doi:10.1093/gbe/evx103. PMC 5534336. PMID 28633296.
  13. Gardner MJ, Hall N, Fung E, White O, Berriman M, Hyman RW, et al. (October 2002). "Genome sequence of the human malaria parasite Plasmodium falciparum". Nature. 419 (6906): 498–511. Bibcode:2002Natur.419..498G. doi:10.1038/nature01097. PMC 3836256. PMID 12368864.
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