NULLOMERS are short sequences of
DNA base pairs that do not occur in
the genome of a species (commonly humans), even though they are
Nullomers must be under a selective pressure
- for example, they may be toxic to the cell. Some nullomers have
been shown to be useful to treat leukemia , breast , and prostate
cancer . They are not useful in healthy cells because normal cells
adapt and become immune to them.
Nullomers are also being developed
for use as
DNA tags to prevent cross contamination when analyzing
crime scene material.
* 1 Background
* 2 Cancer Treatment
* 3 Forensics
* 4 References
Nullomers are naturally available but potentially unused sequences of
DNA . Determining these "forbidden" sequences can improve the
understanding of the basic rules that govern sequence evolution .
Sequencing the entire genome has shown that there is a high level of
non-uniformity in genomic sequences. When a codon is artificially
substituted for a synonymous codon, it often results in a lethal
change and cell death. This is believed to be due to ribosomal
stalling and early termination of protein synthesis. For example, both
AGA and CGA code for arginine in bacteria; however, bacteria almost
never use AGA, and when substituted it proves lethal. Such codon
biases have been seen in all species, and are examples of constraints
on sequence evolution . Other sequences may have selective pressure;
for example, GG-rich sequences are used as sacrificial sinks for
oxidative damage because oxidizing agents are attracted to regions
with GG-rich sequences and then induce strand breakage .
SEQUENCE OF HUMAN NULLOMERS OF 11BP IN LENGTH
NO OCCURRENCE IN THE HUMAN GENOME
CGCTCGACGTA, GTCCGAGCGTA, CGACGAACGGT, CCGATACGTCG
ONE OCCURRENCE IN THE HUMAN GENOME
TACGCGCGACA, CGCGACGCATA, TCGGTACGCTA, TCGCGACCGTA, CGATCGTGCGA,
TWO OCCURRENCES IN THE HUMAN GENOME
CGTCGCTCGAA, TCGCGCGAATA, TCGACGCGATA, ATCGTCGACGA, CTACGCGTCGA,
CGTATACGCGA, CGATTACGCGA, CGATTCGGCGA, CGACGTACCGT, CGACGAACGAG,
THREE OCCURRENCES IN THE HUMAN GENOME
CGCGCATAATA, CGACGGCAGTA, CGAATCGCGTA, CGGTCGTACGA, GCGCGTACCGA,
CGCGTAATCGA, CGTCGTTCGAC, CCGTCGAACGC, ACGCGCGATAT, CGAACGGTCGT,
CGCGTAACGCG, CCGAATACGCG, CATATCGCGCG
Table of the number of nullomers present in different organisms and
the nullomer length
Nullomers have been used as an approach to drug discovery and
development. Nullomer peptides were screened for anti-cancer action .
Absent sequences have short polyarginine tails added to increase
solubility and uptake into the cell, producing peptides called
PolyArgNulloPs. One successful sequence, RRRRRNWMWC, was demonstrated
to have lethal effects in breast and prostate cancer . It damaged
mitochondria by increasing ROS production, which reduced ATP
production, leading to cell growth inhibition and cell death . Normal
cells show a decreased sensitivity to PolyArgNulloPs over time.
Accidental transfer of biological material containing
DNA can produce
misleading results. This is a particularly important consideration in
forensic and crime labs, where mistakes can cause an innocent person
to be convicted of a crime. There was no way to detect if a reference
sample was mislabeled as evidence or if a forensic sample is
contaminated, but a nullomer barcode can be added to reference samples
to distinguish them from evidence on analysis. Tagging can be carried
out during sample collection without affecting genotype or
quantification results. Impregnated filter paper with various
nullomers can be used to soak up and store
DNA samples from a crime
scene, making the technology simple and effective. Tagging with
nullomers can be detected—even when diluted to a million-fold and
spilled on evidence, these tags are still clearly detected. Tagging
in this way supports National Research Council\'s recommendations on
quality control to reduce fraud and mistakes.
* ^ Acquisti, Claudia; Poste, George; Curtiss, David; Kumar, Sudhir
(2007). Salzberg, Steven, ed. "Nullomers: Really a Matter of Natural
Selection?" . PLoS ONE. 2 (10): e1022.
doi :10.1371/journal.pone.0001022 . PMC 1995752 . PMID 17925870 .
* ^ A B C D Alileche, Abdelkrim; Goswami, Jayita; Bourland,
William; Davis, Michael; Hampikian, Greg (2012). "Nullomer derived
anticancer peptides (NulloPs): Differential lethal effects on normal
and cancer cells in vitro". Peptides. 38 (2): 302–11. doi
:10.1016/j.peptides.2012.09.015 . PMID 23000474 . Lay summary – New
Scientist (October 25, 2012).
* ^ A B C D Goswami, Jayita; Davis, Michael C.; Andersen, Tim;
Alileche, Abdelkrim; Hampikian, Greg (2013). "Safeguarding forensic
DNA reference samples with nullomer barcodes". Journal of Forensic and
Legal Medicine. 20: 513–519. doi :10.1016/j.jflm.2013.02.003 . Lay
summary – New Scientist (May 3, 2013).
* ^ A B C Hampikian, Greg; Andersen, Tim (2007). "Absent Sequences:
Nullomers and Primes". Pacific Symposium on Biocomputing: 355–66.
PMID 17990505 .
* ^ Cruz-Vera, Luis Rogelio; Magos-Castro, Marco Antonio;
Zamora-Romo, Efraín; Guarneros, Gabriel (2004). "Ribosome stalling
and peptidyl-tRNA drop-off during translational delay at AGA codons" .
Nucleic Acids Research. 32 (15): 4462–8. doi :10.1093/nar/gkh784 .
PMC 516057 . PMID 15317870 .
* ^ dos Reis, Mario; Savva, Renos; Wernisch, Lorenz (2004).
"Solving the riddle of codon usage preferences: A test for
translational selection" . Nucleic Acids Research. 32 (17): 5036–44.
doi :10.1093/nar/gkh834 . PMC 521650 . PMID 15448185 .
* ^ Friedman, Keith A.; Heller, Adam (2001). "On the Non-Uniform
Distribution of Guanine in Introns of
Human Genes: Possible
Protection of Exons against
Oxidation by Proximal Intron Poly-G
Sequences". The Journal of Physical Chemistry B. 105 (47): 11859–65.