Hypervariable Region

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A hypervariable region (HVR) is a section of DNA or RNA that contains an above-average number of polymorphisms and is therefore particularly variable. Hypervariable regions occur in the DNA of the cell nucleus as well as in the control region of the mitochondrial DNA and in the RNA of the hepatitis C virus .

Hypervariable region of the mtDNA

Human mitochondrial genome with hypervariable regions I to III (green) within the mtDNA control region (gray)

There are two hypervariable regions in mitochondrial DNA, HVR1 and HVR2. While HVR1 is contiguous at position 16024-16383, HVR2 consists of two sections, which are subdivided as HVR-II at position 57-372 and HVR-III at position 438-574. Due to the high variability, HVR1 and HVR2 are used for DNA analysis and to determine the haplogroup .

In some bony fish such as Protacanthopterygii and Gadidae , the mtDNA control region changes evolutionarily relatively slowly, even more slowly than the mitochondrial genes . The reason for this is still unknown.

Hypervariable regions of the DNA of the nucleus

In the DNA of the cell nucleus, hypervariable regions occur in the section of the antigen- binding region ( complementarity-determining region , CDR) of genes for antibodies and the T-cell receptor . They arise there both in the CDR of the light chain and in the CDR of the heavy chain of the antibodies through VDJ recombination and somatic hypermutation and serve to enable antibodies to adapt to new or changed antigens in the course of an immune reaction .

Rab proteins each have a hypervariable region at their C termini , which determines the respective localization within a cell . Analog function has the hypervariable region of the Ras - protein KRAS 4B and small GTPases such as Rac .

Hypervariable region of the hepatitis C virus RNA

The gene of the envelope protein 2 of hepatitis C virus has N -terminal a hypervariable region as antigenic drift of the immune evasion serves antibodies as part of an immune response against the Hepatitis C virus.

Individual evidence

  1. ↑ M. van Oven, M. Kayser: Updated comprehensive phylogenetic tree of global human mitochondrial DNA variation . In: Human Mutation . 30, No. 2, February 2009, pp. E386-94. doi : 10.1002 / humu.20921 . PMID 18853457 .
  2. ↑ PhyloTree mt . "Annotated mtDNA reference sequences: revised Cambridge Reference Sequence (rCRS)" . Retrieved February 4, 2016.
  3. ↑ Hirohiko Takeshima, Kei-ichiro Iguchi, Mutsumi Nishida: Unexpected Ceiling of Genetic Differentiation in the Control Region of the Mitochondrial DNA between Different Subspecies of the Ayu, Plecoglossus altivelis . In: Zool. Sci. (2005), Volume 22, Issue 4, pp. 401-410. doi : 10.2108 / zsj.22.401 .
  4. ↑ Michael Stein, Paul Zei, Gloria Hwang, Radhika Breaden: Cracking The Boards: USMLE Step 1 . The Princeton Review , 2000, ISBN 9780375761638 (Retrieved September 5, 2011): "Antibodies are remarkably specific, thanks to hypervariable regions in both light and heavy chains."
  5. ↑ P. Chavrier, JP Gorvel, E. Stelzer, K. Simons, J. Gruenberg, M. Zerial: Hypervariable C-terminal domain of rab proteins acts as a targeting signal. In: Nature . Volume 353, Number 6346, October 1991, pp. 769-772, doi : 10.1038 / 353769a0 , PMID 1944536 .
  6. ↑ A. Banerjee, H. Jang, R. Nussinov, V. Gaponenko: The disordered hypervariable region and the folded catalytic domain of oncogenic K-Ras4B partner in phospholipid binding. In: Current opinion in structural biology. Volume 36, February 2016, pp. 10-17, doi : 10.1016 / j.sbi.2015.11.010 , PMID 26709496 , PMC 4785042 (free full text).
  7. ↑ BD Lam, PL Hordijk: The Rac1 hypervariable region in targeting and signaling: a tail of many stories. In: Small GTPases. Volume 4, number 2, 2013 Apr-Jun, pp. 78-89, doi : 10.4161 / sgtp.23310 , PMID 23354415 , PMC 3747260 (free full text).
  8. ↑ J. Prentoe, J. Bukh: Hypervariable Region 1 in Envelope Protein 2 of Hepatitis C Virus: A Linchpin in Neutralizing Antibody Evasion and Viral Entry. In: Frontiers in immunology. Volume 9, 2018, p. 2146, doi : 10.3389 / fimmu.2018.02146 , PMID 30319614 , PMC 6170631 (free full text).
  9. ↑ MU Mondelli, A. Cerino, A. Meola, A. Nicosia: Variability or conservation of hepatitis C virus hypervariable region 1? Implications for immune responses. In: Journal of biosciences. Volume 28, Number 3, April 2003, pp. 305-310, PMID 12734408 .