MtDNA control region explained

Mitochondrial DNA control region secondary structure A
Symbol:	mtDNA ssA
Rfam:	RF01853
Rna Type:	Antisense RNA
Tax Domain:	Mammalia

The mtDNA control region is an area of the mitochondrial genome which is non-coding DNA. This region controls RNA and DNA synthesis.^[1] It is the most polymorphic region of the human mtDNA genome,^[2] with polymorphism concentrated in hypervariable regions. The average nucleotide diversity in these regions is 1.7%.^[3] Despite this variability, an RNA transcript from this region has a conserved secondary structure (pictured) which has been found to be under selective pressure.^[4]

The mtDNA control region contains the origin of replication of one strand, and the origin of transcription for both strands.^[5] There is also an open reading frame thought to code for 7s ribosomal RNA in humans but not in mice or cows, where it has been deleted.^[6]

Distinction from D-loop

The control region and mtDNA D-loop are sometimes used synonymously in the literature; specifically the control region includes the D-loop along with adjacent transcription promoter regions. For this reason, the control region is also known by the acronym DLP, standing for D-Loop and associated Promoters.^[7]

Endurance study

mtDNA control region haplotypes have been linked with endurance capacity in human subjects.^[8] A 2002 study sequenced the control region of 55 subjects and compared their haplotype with the increase in VO₂ max after an eight-week training program. They found that different haplotypes were significantly linked with the subjects' endurance. It was speculated that this was because the control region affects replication and transcription in the mitochondria.

See also

• D-loop
• Hypervariable region

Further reading

• Stoneking M . Hypervariable Sites in the mtDNA Control Region Are Mutational Hotspots . Am. J. Hum. Genet. . 67 . 4 . 1029–32 . October 2000 . 10968778 . 1287875 . 10.1086/303092 .
• Sachidanandam R, Weissman D, Schmidt SC, etal . A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms . Nature . 409 . 6822 . 928–33 . February 2001 . 11237013 . 10.1038/35057149. free .

External links

• EMPOP - the Mitochondrial DNA Control Region Database

Notes and References

1. http://www.geneticorigins.org/mito/theory3.html Structure of the Mitochondrial Genome
2. Stoneking M, Hedgecock D, Higuchi RG, Vigilant L, Erlich HA . Population variation of human mtDNA control region sequences detected by enzymatic amplification and sequence-specific oligonucleotide probes . Am. J. Hum. Genet. . 48 . 2 . 370–82 . February 1991 . 1990843 . 1683035 .
3. Aquadro CF, Greenberg BD . Human Mitochondrial DNA Variation and Evolution: Analysis of Nucleotide Sequences from Seven Individuals . Genetics . 103 . 2 . 287–312 . February 1983 . 10.1093/genetics/103.2.287 . 6299878 . 1219980 . 2010-07-29.
4. Pereira F, Soares P, Carneiro J, etal . Evidence for variable selective pressures at a large secondary structure of the human mitochondrial DNA control region . Mol. Biol. Evol. . 25 . 12 . 2759–70 . December 2008 . 18845547 . 10.1093/molbev/msn225 . free .
5. Anderson S, Bankier AT, Barrell BG, etal . Sequence and organization of the human mitochondrial genome . Nature . 290 . 5806 . 457–65 . April 1981 . 7219534 . 10.1038/290457a0. 1981Natur.290..457A . 4355527 .
6. Ojala D, Montoya J, Attardi G . tRNA punctuation model of RNA processing in human mitochondria . Nature . 290 . 5806 . 470–4 . April 1981 . 7219536 . 10.1038/290470a0. 1981Natur.290..470O . 4323371 .
7. Michikawa Y, Mazzucchelli F, Bresolin N, Scarlato G, Attardi G . Aging-dependent large accumulation of point mutations in the human mtDNA control region for replication . Science . 286 . 5440 . 774–9 . October 1999 . 10531063 . 10.1126/science.286.5440.774.
8. Murakami H, Ota A, Simojo H, Okada M, Ajisaka R, Kuno S . Polymorphisms in control region of mtDNA relates to individual differences in endurance capacity or trainability . Jpn. J. Physiol. . 52 . 3 . 247–56 . June 2002 . 12230801 . 10.2170/jjphysiol.52.247. free .