D box gene transcriptions

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Associate Editor(s)-in-Chief: Henry A. Hoff

File:RF00071.jpg
This example of a C/D box is a small nucleolar RNA 73 (snoRNA U73). Credit: Rfam database (RF00071).{{free media}}

For "box C/D snoRNAs, boxes C and D and an adjoining stem form a vital structure, known as the box C/D motif."[1]

In snoRNA U73 on the right, from the right side, the D box is AGUCY. In 5' to 3' direction, the D box is YCUGA.

Degenerate nucleotides

For transcription, U (in RNA) is T, Y=(C or T) and R=(A or G).

Consensus sequences

File:U14 snoRNA.png
This U14 snoRNA from Saccharomyces cerevisiae shows structure and genomic organization. Credit: Dmitry A.Samarsky, Maurille J.Fournier, Robert H.Singer and Edouard Bertrand.{{fairuse}}

Shown in the image on the right is the D box (3'-AGUCUG-5'). Substituting T for U yields D box = 3'-AGTCTG-5' in the transcription direction on the template strand.

"Members of the box C/D snoRNA family, which are the subject of the present report, possess characteristic sequence elements known as box C (UGAUGA) and box D (GUCUGA)."[1]

D-box (TGAGTGG).[2]

Hypotheses

  1. The D boxes are not involved in the transcription of A1BG.
  2. The promoters of A1BG do not contain a Samarsky D box.

(Samarsky) samplings

For the Basic programs (starting with SuccessablesDbox.bas) written to compare nucleotide sequences with the sequences on either the template strand (-), or coding strand (+), of the DNA, in the negative direction (-), or the positive direction (+), the programs are, are looking for, and found:

  1. negative strand in the negative direction (from ZSCAN22 to A1BG) is SuccessablesDbox--.bas, looking for 3'-AGTCTG-5', 1, 3'-AGTCTG-5', 2947,
  2. negative strand in the positive direction (from ZNF497 to A1BG) is SuccessablesDbox-+.bas, looking for 3'-AGTCTG-5', 1, 3'-AGTCTG-5', 3923,
  3. positive strand in the negative direction is SuccessablesDbox+-.bas, looking for 3'-AGTCTG-5', 1, 3'-AGTCTG-5', 1355,
  4. positive strand in the positive direction is SuccessablesDbox++.bas, looking for 3'-AGTCTG-5', 0,
  5. complement, negative strand, negative direction is SuccessablesDboxc--.bas, looking for 3'-TCAGAC-5', 1, 3'-TCAGAC-5', 1355,
  6. complement, negative strand, positive direction is SuccessablesDboxc-+.bas, looking for 3'-TCAGAC-5', 0,
  7. complement, positive strand, negative direction is SuccessablesDboxc+-.bas, looking for 3'-TCAGAC-5', 1, 3'-TCAGAC-5', 2947,
  8. complement, positive strand, positive direction is SuccessablesDboxc++.bas, looking for 3'-TCAGAC-5', 1, 3'-TCAGAC-5', 3923,
  9. inverse complement, negative strand, negative direction is SuccessablesDboxci--.bas, looking for 3'-CAGACT-5', 0,
  10. inverse complement, negative strand, positive direction is SuccessablesDboxci-+.bas, looking for 3'-CAGACT-5', 2, 3'-CAGACT-5', 1744, 3'-CAGACT-5', 2416,
  11. inverse complement, positive strand, negative direction is SuccessablesDboxci+-.bas, looking for 3'-CAGACT-5', 2, 3'-CAGACT-5', 15, 3'-CAGACT-5', 1616,
  12. inverse complement, positive strand, positive direction is SuccessablesDboxci++.bas, looking for 3'-CAGACT-5', 3, 3'-CAGACT-5', 2943, 3'-CAGACT-5', 3006, 3'-CAGACT-5', 3924,
  13. inverse, negative strand, negative direction, is SuccessablesDboxi--.bas, looking for 3'-GTCTGA-5', 2, 3'-GTCTGA-5', 15, 3'-GTCTGA-5', 1616,
  14. inverse, negative strand, positive direction, is SuccessablesDboxi-+.bas, looking for 3'-GTCTGA-5', 3, 3'-GTCTGA-5', 2943, 3'-GTCTGA-5', 3006, 3'-GTCTGA-5', 3924,
  15. inverse, positive strand, negative direction, is SuccessablesDboxi+-.bas, looking for 3'-GTCTGA-5', 0,
  16. inverse, positive strand, positive direction, is SuccessablesDboxi++.bas, looking for 3'-GTCTGA-5', 2, 3'-GTCTGA-5', 1744, 3'-GTCTGA-5', 2416.

(Samarsky) distal promoters

Negative strand, negative direction: 5'-AGTCTG-3' at 2947, and complement.

Positive strand, negative direction: 5'-CAGACT-3' at 1616, 5'-AGTCTG-3' at 1355, 5'-CAGACT-3' at 15, and complements.

Negative strand, positive direction: 5'-AGTCTG-3' at 3923, 5'-CAGACT-3' at 2416, and complements.

Positive strand, positive direction: 5'-CAGACT-3' at 3924, 5'-CAGACT-3' at 3006, 5'-CAGACT-3' at 2943, and complements.

D boxes

The human ribosomal protein L11 gene (HRPL11) has [...] two potential snRNA-coding sequences in intron 4: [...] a D box beginning at +4237 (TCCTG), [...].[3]

(Voronina) samplings

For the Basic programs testing consensus sequence 5'-TCCTG-3' (starting with SuccessablesAAA.bas) written to compare nucleotide sequences with the sequences on either the template strand (-), or coding strand (+), of the DNA, in the negative direction (-), or the positive direction (+), the programs are, are looking for, and found:

  1. negative strand, negative direction, looking for 5'-TCCTG-3', 4, 5'-TCCTG-3' at 4467, 5'-TCCTG-3' at 3755, 5'-TCCTG-3' at 3639, 5'-TCCTG-3' at 3388, and complements.
  2. negative strand, positive direction, looking for 5'-TCCTG-3', 10, 5'-TCCTG-3' at 4408, 5'-TCCTG-3' at 4185, 5'-TCCTG-3' at 3621, 5'-TCCTG-3' at 3295, 5'-TCCTG-3' at 2519, 5'-TCCTG-3' at 2500, 5'-TCCTG-3' at 2210, 5'-TCCTG-3' at 1775, 5'-TCCTG-3' at 1117, 5'-TCCTG-3' at 143, and complements.
  3. positive strand, negative direction, looking for 5'-TCCTG-3', 5, 5'-TCCTG-3' at 4545, 5'-TCCTG-3' at 3905, 5'-TCCTG-3' at 1910, 5'-TCCTG-3' at 1840, 5'-TCCTG-3' at 595, and complements.
  4. positive strand, positive direction, looking for 5'-TCCTG-3', 4, 5'-TCCTG-3' at 4251, 5'-TCCTG-3' at 3130, 5'-TCCTG-3' at 2459, 5'-TCCTG-3' at 1669, and complements.
  5. complement, negative strand, negative direction, looking for 5'-AGGAC-3', 5, 5'-AGGAC-3' at 4545, 5'-AGGAC-3' at 3905, 5'-AGGAC-3' at 1910, 5'-AGGAC-3' at 1840, 5'-AGGAC-3' at 595.
  6. complement, negative strand, positive direction, looking for 5'-AGGAC-3', 4, 5'-AGGAC-3' at 4251, 5'-AGGAC-3' at 3130, 5'-AGGAC-3' at 2459, 5'-AGGAC-3' at 1669.
  7. complement, positive strand, negative direction, looking for 5'-AGGAC-3', 4, 5'-AGGAC-3' at 4467, 5'-AGGAC-3' at 3755, 5'-AGGAC-3' at 3639, 5'-AGGAC-3' at 3388.
  8. complement, positive strand, positive direction, looking for 5'-AGGAC-3', 10, 5'-AGGAC-3' at 4408, 5'-AGGAC-3' at 4185, 5'-AGGAC-3' at 3621, 5'-AGGAC-3' at 3295, 5'-AGGAC-3' at 2519, 5'-AGGAC-3' at 2500, 5'-AGGAC-3' at 2210, 5'-AGGAC-3' at 1775, 5'-AGGAC-3' at 1117, 5'-AGGAC-3' at 143.
  9. inverse complement, negative strand, negative direction, looking for 5'-CAGGA-3', 0.
  10. inverse complement, negative strand, positive direction, looking for 5'-CAGGA-3', 7, 5'-CAGGA-3' at 3869, 5'-CAGGA-3' at 3572, 5'-CAGGA-3' at 3129, 5'-CAGGA-3' at 2746, 5'-CAGGA-3' at 2621, 5'-CAGGA-3' at 708, 5'-CAGGA-3' at 425, and complements.
  11. inverse complement, positive strand, negative direction, looking for 5'-CAGGA-3', 23, 5'-CAGGA-3' at 4437, 5'-CAGGA-3' at 4283, 5'-CAGGA-3' at 4171, 5'-CAGGA-3' at 4139, 5'-CAGGA-3' at 3250, 5'-CAGGA-3' at 3218, 5'-CAGGA-3' at 3111, 5'-CAGGA-3' at 2690, 5'-CAGGA-3' at 2588, 5'-CAGGA-3' at 2368, 5'-CAGGA-3' at 2251, 5'-CAGGA-3' at 2135, 5'-CAGGA-3' at 1942, 5'-CAGGA-3' at 1824, 5'-CAGGA-3' at 1289, 5'-CAGGA-3' at 1276, 5'-CAGGA-3' at 998, 5'-CAGGA-3' at 985, 5'-CAGGA-3' at 851, 5'-CAGGA-3' at 832, 5'-CAGGA-3' at 715, 5'-CAGGA-3' at 579, 5'-CAGGA-3' at 442, and complements.
  12. inverse complement, positive strand, positive direction, looking for 5'-CAGGA-3', 5, 5'-CAGGA-3' at 3864, 5'-CAGGA-3' at 3620, 5'-CAGGA-3' at 2999, 5'-CAGGA-3' at 758, 5'-CAGGA-3' at 219, and complements.
  13. inverse negative strand, negative direction, looking for 5'-GTCCT-3', 23, 5'-GTCCT-3' at 4437, 5'-GTCCT-3' at 4283, 5'-GTCCT-3' at 4171, 5'-GTCCT-3' at 4139, 5'-GTCCT-3' at 3250, 5'-GTCCT-3' at 3218, 5'-GTCCT-3' at 3111, 5'-GTCCT-3' at 2690, 5'-GTCCT-3' at 2588, 5'-GTCCT-3' at 2368, 5'-GTCCT-3' at 2251, 5'-GTCCT-3' at 2135, 5'-GTCCT-3' at 1942, 5'-GTCCT-3' at 1824, 5'-GTCCT-3' at 1289, 5'-GTCCT-3' at 1276, 5'-GTCCT-3' at 998, 5'-GTCCT-3' at 985, 5'-GTCCT-3' at 851, 5'-GTCCT-3' at 832, 5'-GTCCT-3' at 715, 5'-GTCCT-3' at 579, 5'-GTCCT-3' at 442.
  14. inverse negative strand, positive direction, looking for 5'-GTCCT-3', 5, 5'-GTCCT-3' at 3864, 5'-GTCCT-3' at 3620, 5'-GTCCT-3' at 2999, 5'-GTCCT-3' at 758, 5'-GTCCT-3' at 219.
  15. inverse positive strand, negative direction, looking for 5'-GTCCT-3', 0.
  16. inverse positive strand, positive direction, looking for 5'-GTCCT-3', 7, 5'-GTCCT-3' at 3869, 5'-GTCCT-3' at 3572, 5'-GTCCT-3' at 3129, 5'-GTCCT-3' at 2746, 5'-GTCCT-3' at 2621, 5'-GTCCT-3' at 708, 5'-GTCCT-3' at 425.

DVor core promoters

Negative strand, negative direction: 5'-TCCTG-3' at 4467, and complement.

Positive strand, negative direction: 5'-TCCTG-3' at 4545, 5'-CAGGA-3' at 4437, and complements.

Negative strand, positive direction: 5'-TCCTG-3' at 4408, and complement.

DVor proximal promoters

Positive strand, negative direction: 5'-CAGGA-3' at 4283, and complement.

Negative strand, positive direction: 5'-TCCTG-3' at 4185, and complement.

Positive strand, positive direction: 5'-TCCTG-3' at 4251, and complement.

DVor distal promoters

Negative strand, negative direction: 5'-TCCTG-3' at 3755, 5'-TCCTG-3' at 3639, 5'-TCCTG-3' at 3388, and complements.

Positive strand, negative direction: 5'-CAGGA-3' at 4171, 5'-CAGGA-3' at 4139, 5'-TCCTG-3' at 3905, 5'-CAGGA-3' at 3250, 5'-CAGGA-3' at 3218, 5'-CAGGA-3' at 3111, 5'-CAGGA-3' at 2690, 5'-CAGGA-3' at 2588, 5'-CAGGA-3' at 2368, 5'-CAGGA-3' at 2251, 5'-CAGGA-3' at 2135, 5'-CAGGA-3' at 1942, 5'-TCCTG-3' at 1910, 5'-TCCTG-3' at 1840, 5'-CAGGA-3' at 1824, 5'-CAGGA-3' at 1289, 5'-CAGGA-3' at 1276, 5'-CAGGA-3' at 998, 5'-CAGGA-3' at 985, 5'-CAGGA-3' at 851, 5'-CAGGA-3' at 832, 5'-CAGGA-3' at 715, 5'-TCCTG-3' at 595, 5'-CAGGA-3' at 579, 5'-CAGGA-3' at 442, and complements.

Negative strand, positive direction: 5'-CAGGA-3' at 3869, 5'-TCCTG-3' at 3621, 5'-CAGGA-3' at 3572, 5'-TCCTG-3' at 3295, 5'-CAGGA-3' at 3129, 5'-CAGGA-3' at 2746, 5'-CAGGA-3' at 2621, 5'-TCCTG-3' at 2519, 5'-TCCTG-3' at 2500, 5'-TCCTG-3' at 2210, 5'-TCCTG-3' at 1775, 5'-TCCTG-3' at 1117, 5'-CAGGA-3' at 708, 5'-CAGGA-3' at 425, 5'-TCCTG-3' at 143, and complements.

Positive strand, positive direction: 5'-CAGGA-3' at 3864, 5'-CAGGA-3' at 3620, 5'-TCCTG-3' at 3130, 5'-CAGGA-3' at 2999, 5'-TCCTG-3' at 2459, 5'-TCCTG-3' at 1669, 5'-CAGGA-3' at 758, 5'-CAGGA-3' at 219, and complements.

(Johnson) samplings

TCTCACATT(A/C)AATAAGTCA is a D-box.[4]

For the Basic programs testing consensus sequence 5'-TCTCACATT(A/C)AATAAGTCA-3' (starting with SuccessablesAAA.bas) written to compare nucleotide sequences with the sequences on either the template strand (-), or coding strand (+), of the DNA, in the negative direction (-), or the positive direction (+), the programs are, are looking for, and found:

  1. negative strand, negative direction, looking for 5'-TCTCACATT(A/C)AATAAGTCA-3', 0.
  2. negative strand, positive direction, looking for 5'-TCTCACATT(A/C)AATAAGTCA-3', 0.
  3. positive strand, negative direction, looking for 5'-TCTCACATT(A/C)AATAAGTCA-3', 0.
  4. positive strand, positive direction, looking for 5'-TCTCACATT(A/C)AATAAGTCA-3', 0.
  5. complement, negative strand, negative direction, looking for 5'-AGAGTGTAA(G/T)TTATTCAGT-3', 0.
  6. complement, negative strand, positive direction, looking for 5'-AGAGTGTAA(G/T)TTATTCAGT-3', 0.
  7. complement, positive strand, negative direction, looking for 5'-AGAGTGTAA(G/T)TTATTCAGT-3', 0.
  8. complement, positive strand, positive direction, looking for 5'-AGAGTGTAA(G/T)TTATTCAGT-3', 0.
  9. inverse complement, negative strand, negative direction, looking for 5'-TGACTTATT(G/T)AATGTGAGA-3', 0.
  10. inverse complement, negative strand, positive direction, looking for 5'-TGACTTATT(G/T)AATGTGAGA-3', 0.
  11. inverse complement, positive strand, negative direction, looking for 5'-TGACTTATT(G/T)AATGTGAGA-3', 0.
  12. inverse complement, positive strand, positive direction, looking for 5'-TGACTTATT(G/T)AATGTGAGA-3', 0.
  13. inverse negative strand, negative direction, looking for 5'-ACTGAATAA(A/C)TTACACTCT-3', 0.
  14. inverse negative strand, positive direction, looking for 5'-ACTGAATAA(A/C)TTACACTCT-3', 0.
  15. inverse positive strand, negative direction, looking for 5'-ACTGAATAA(A/C)TTACACTCT-3', 0.
  16. inverse positive strand, positive direction, looking for 5'-ACTGAATAA(A/C)TTACACTCT-3', 0.

(Mracek) samplings

There is another promoter D box, or D-box: "Located in the region [...] is a single D-box element (5′-GTTGTATAAC-3′) with a distinct sequence from that of the functional D-box identified in the per2 promoter (5′-CTTATGTAAA-3′) [21]."[5]

(Mracek1) samplings

For the Basic programs testing consensus sequence 5'-GTTGTATAAC-3' (starting with SuccessablesMra1.bas) written to compare nucleotide sequences with the sequences on either the template strand (-), or coding strand (+), of the DNA, in the negative direction (-), or the positive direction (+), the programs are, are looking for, and found:

  1. negative strand, negative direction, looking for 5'-GTTGTATAAC-3', 0.
  2. negative strand, positive direction, looking for 5'-GTTGTATAAC-3', 0.
  3. positive strand, negative direction, looking for 5'-GTTGTATAAC-3', 0.
  4. positive strand, positive direction, looking for 5'-GTTGTATAAC-3', 0.
  5. complement, negative strand, negative direction, looking for 5'-CAACATATTG-3', 0.
  6. complement, negative strand, positive direction, looking for 5'-CAACATATTG-3', 0.
  7. complement, positive strand, negative direction, looking for 5'-CAACATATTG-3', 0.
  8. complement, positive strand, positive direction, looking for 5'-CAACATATTG-3', 0.
  9. inverse complement, negative strand, negative direction, looking for 5'-GTTATACAAC-3', 0.
  10. inverse complement, negative strand, positive direction, looking for 5'-GTTATACAAC-3', 0.
  11. inverse complement, positive strand, negative direction, looking for 5'-GTTATACAAC-3', 0.
  12. inverse complement, positive strand, positive direction, looking for 5'-GTTATACAAC-3', 0.
  13. inverse negative strand, negative direction, looking for 5'-CAATATGTTG-3', 0.
  14. inverse negative strand, positive direction, looking for 5'-CAATATGTTG-3', 0.
  15. inverse positive strand, negative direction, looking for 5'-CAATATGTTG-3', 0.
  16. inverse positive strand, positive direction, looking for 5'-CAATATGTTG-3', 0.

(Mracek2) samplings

For the Basic programs testing consensus sequence 5'-CTTATGTAAA-3' (starting with SuccessablesMra2.bas) written to compare nucleotide sequences with the sequences on either the template strand (-), or coding strand (+), of the DNA, in the negative direction (-), or the positive direction (+), the programs are, are looking for, and found:

  1. negative strand, negative direction, looking for 5'-CTTATGTAAA-3', 0.
  2. negative strand, positive direction, looking for 5'-CTTATGTAAA-3', 0.
  3. positive strand, negative direction, looking for 5'-CTTATGTAAA-3', 0.
  4. positive strand, positive direction, looking for 5'-CTTATGTAAA-3', 0.
  5. complement, negative strand, negative direction, looking for 5'-TTTTTTTT-3', 0.
  6. complement, negative strand, positive direction, looking for 5'-TTTTTTTT-3', 0.
  7. complement, positive strand, negative direction, looking for 5'-TTTTTTTT-3', 0.
  8. complement, positive strand, positive direction, looking for 5'-TTTTTTTT-3', 0.
  9. inverse complement, negative strand, negative direction, looking for 5'-TTTTTTTT-3', 0.
  10. inverse complement, negative strand, positive direction, looking for 5'-TTTTTTTT-3', 0.
  11. inverse complement, positive strand, negative direction, looking for 5'-TTTTTTTT-3', 0.
  12. inverse complement, positive strand, positive direction, looking for 5'-TTTTTTTT-3', 0.
  13. inverse negative strand, negative direction, looking for 5'-AAAAAAAA-3', 0.
  14. inverse negative strand, positive direction, looking for 5'-AAAAAAAA-3', 0.
  15. inverse positive strand, negative direction, looking for 5'-AAAAAAAA-3', 0.
  16. inverse positive strand, positive direction, looking for 5'-AAAAAAAA-3', 0.

AAA core promoters

AAA proximal promoters

AAA distal promoters

Consensus sequence (Motojima)

D-box (TGAGTGG).[2]

(Motojima) samplings

Copying the consensus of the D-box: 5'-TGAGTGG-3' and putting the sequence in "⌘F" finds no locations between ZSCAN22 and A1BG and one between ZNF497 and A1BG as can be found by the computer programs.

For the Basic programs testing consensus sequence 5'-AAAAAAAA-3' (starting with SuccessablesAAA.bas) written to compare nucleotide sequences with the sequences on either the template strand (-), or coding strand (+), of the DNA, in the negative direction (-), or the positive direction (+), the programs are, are looking for, and found:

  1. negative strand, negative direction, looking for 5'-AAAAAAAA-3', 0.
  2. negative strand, positive direction, looking for 5'-AAAAAAAA-3', 0.
  3. positive strand, negative direction, looking for 5'-AAAAAAAA-3', 0.
  4. positive strand, positive direction, looking for 5'-AAAAAAAA-3', 0.
  5. complement, negative strand, negative direction, looking for 5'-TTTTTTTT-3', 0.
  6. complement, negative strand, positive direction, looking for 5'-TTTTTTTT-3', 0.
  7. complement, positive strand, negative direction, looking for 5'-TTTTTTTT-3', 0.
  8. complement, positive strand, positive direction, looking for 5'-TTTTTTTT-3', 0.
  9. inverse complement, negative strand, negative direction, looking for 5'-TTTTTTTT-3', 0.
  10. inverse complement, negative strand, positive direction, looking for 5'-TTTTTTTT-3', 0.
  11. inverse complement, positive strand, negative direction, looking for 5'-TTTTTTTT-3', 0.
  12. inverse complement, positive strand, positive direction, looking for 5'-TTTTTTTT-3', 0.
  13. inverse negative strand, negative direction, looking for 5'-AAAAAAAA-3', 0.
  14. inverse negative strand, positive direction, looking for 5'-AAAAAAAA-3', 0.
  15. inverse positive strand, negative direction, looking for 5'-AAAAAAAA-3', 0.
  16. inverse positive strand, positive direction, looking for 5'-AAAAAAAA-3', 0.

AAA core promoters

AAA proximal promoters

AAA distal promoters

Acknowledgements

The content on this page was first contributed by: Henry A. Hoff.

Initial content for this page in some instances came from Wikiversity.

See also

References

  1. 1.0 1.1 Dmitry A.Samarsky, Maurille J.Fournier, Robert H.Singer and Edouard Bertrand (1 July 1998). "The snoRNA box C/D motif directs nucleolar targeting and also couples snoRNA synthesis and localization" (PDF). The European Molecular Biology Organization (EMBO) Journal. 17 (13): 3747–3757. doi:10.1093/emboj/17.13.3747. PMID 9649444. Retrieved 2017-02-04.
  2. 2.0 2.1 Masaru Motojima, Takao Ando and Toshimasa Yoshioka (10 July 2000). "Sp1-like activity mediates angiotensin-II-induced plasminogen-activator inhibitor type-1 (PAI-1) gene expression in mesangial cells" (PDF). Biomedical Journal. 349 (2): 435–441. doi:10.1042/0264-6021:3490435. PMID 10880342. Retrieved 13 August 2020.
  3. E. N. Voronina, T. D. Kolokol’tsova, E. A. Nechaeva, and M. L. Filipenko (2003). "Structural–Functional Analysis of the Human Gene for Ribosomal Protein L11" (PDF). Molecular Biology. 37 (3): 362–371. Retrieved 11 April 2019.
  4. PA Johnson, D Bunick, NB Hecht (1991). "Protein Binding Regions in the Mouse and Rat Protamine-2 Genes" (PDF). Biology of Reproduction. 44 (1): 127–134. Retrieved 6 April 2019.
  5. Philipp Mracek, Cristina Santoriello, M. Laura Idda, Cristina Pagano, Zohar Ben-Moshe, Yoav Gothilf, Daniela Vallone, Nicholas S. Foulkes (December 6, 2012). "Regulation of per and cry Genes Reveals a Central Role for the D-Box Enhancer in Light-Dependent Gene Expression". PLoS ONE. 7 (12): e51278. doi:10.1371/journal.pone.0051278. Retrieved 10 February 2019.

External links