Genetic recombination
Genetic recombination
Structure of the Holliday junction intermediate in genetic recombination. The four separate DNA strands are coloured red, blue, green and yellow.[95]
Further information: Genetic recombination
Recombination involves the breakage and rejoining of two chromosomes (M
and F) to produce two re-arranged chromosomes (C1 and C2).
A DNA helix usually does not interact with other segments of DNA,
and in human cells the different chromosomes even occupy separate areas
in the nucleus called "chromosome territories".[96]
This physical separation of different chromosomes is important for the
ability of DNA to ******** as a stable repository for information, as
one of the few times chromosomes interact is during chromosomal crossover when they recombine. Chromosomal crossover is when two DNA helices break, swap a section and then rejoin.
Recombination allows chromosomes to exchange genetic information and
produces new combinations of genes, which increases the efficiency of natural selection and can be important in the rapid evolution of new proteins.[97] Genetic recombination can also be involved in DNA repair, particularly in the cell`s response to double-strand breaks.[98]
The most common form of chromosomal crossover is homologous recombination,
where the two chromosomes involved share very similar sequences.
Non-homologous recombination can be damaging to cells, as it can
produce chromosomal translocations and genetic abnormalities. The recombination reaction is catalyzed by enzymes known as recombinases, such as RAD51.[99] The first step in recombination is a double-stranded break either caused by an endonuclease or damage to the DNA.[100] A series of steps catalyzed in part by the recombinase then leads to joining of the two helices by at least one Holliday junction,
in which a segment of a single strand in each helix is annealed to the
complementary strand in the other helix. The Holliday junction is a
tetrahedral junction structure that can be moved along the pair of
chromosomes, swapping one strand for another. The recombination
reaction is then halted by cleavage of the junction and re-ligation of
the released DNA.[101]
Evolution of DNA metabolism
Further information: RNA world hypothesis
DNA contains the genetic information that allows all modern living
things to ********, grow and reproduce. However, it is unclear how long
in the 4-billion-year history of life
DNA has performed this ********, as it has been proposed that the
earliest forms of life may have used RNA as their genetic material.[90][102] RNA may have acted as the central part of early cell metabolism as it can both transmit genetic information and carry out catalysis as part of ribozymes.[103] This ancient RNA world where nucleic acid would have been used for both catalysis and genetics may have influenced the evolution
of the current genetic code based on four nucleotide bases. This would
occur since the number of unique bases in such an organism is a
trade-off between a small number of bases increasing replication
accuracy and a large number of bases increasing the catalytic
efficiency of ribozymes.[104]
Unfortunately, there is no direct evidence of ancient genetic
systems, as recovery of DNA from most fossils is impossible. This is
because DNA will survive in the environment for less than one million
years and slowly degrades into short fragments in solution.[105]
Although claims for older DNA have been made, most notably a report of
the isolation of a viable bacterium from a salt crystal 250-million
years old,[106] these claims are controversial and have been disputed.[107][108]
Uses in technology
Genetic engineering
Further information: Molecular biology and genetic engineering
Modern biology and biochemistry make intensive use of recombinant DNA technology. Recombinant DNA is a man-made DNA sequence that has been assembled from other DNA sequences. They can be transformed into organisms in the form of plasmids or in the appropriate format, by using a viral vector.[109] The genetically modified organisms produced can be used to produce products such as recombinant proteins, used in medical research,[110] or be grown in agriculture.[111][112]
Forensics
Further information: Genetic fingerprinting
Forensic scientists can use DNA in blood, semen, skin, saliva or hair at a crime scene to identify a perpetrator. This process is called genetic fingerprinting, or more accurately, DNA profiling. In DNA profiling, the lengths of variable sections of repetitive DNA, such as short tandem repeats and minisatellites, are compared between people. This method is usually an extremely reliable technique for identifying a criminal.[113] However, identification can be complicated if the scene is contaminated with DNA from several people.[114] DNA profiling was developed in 1984 by British geneticist Sir Alec Jeffreys,[115] and first used in forensic science to convict Colin Pitchfork in the 1988 Enderby murders case.[116]
People convicted of certain types of crimes may be required to provide
a sample of DNA for a database. This has helped investigators solve old
cases where only a DNA sample was obtained from the scene. DNA
profiling can also be used to identify victims of mass casualty
incidents.[117]
Bioinformatics
Further information: Bioinformatics
Bioinformatics involves the manipulation, searching, and data mining of DNA sequence data. The development of techniques to store and search DNA sequences have led to widely-applied advances in computer science, especially string searching algorithms, machine learning and database theory.[118]
String searching or matching algorithms, which find an occurrence of a
sequence of letters inside a larger sequence of letters, were developed
to search for specific sequences of nucleotides.[119] In other applications such as text editors,
even simple algorithms for this problem usually suffice, but DNA
sequences cause these algorithms to exhibit near-worst-case behaviour
due to their small number of distinct characters. The related problem
of sequence alignment aims to identify homologous sequences and locate the specific mutations that make them distinct. These techniques, especially multiple sequence alignment, are used in studying phylogenetic relationships and protein ********.[120] Data sets representing entire genomes` worth of DNA sequences, such as those produced by the Human Genome Project,
are difficult to use without annotations, which label the locations of
genes and regulatory elements on each chromosome. Regions of DNA
sequence that have the characteristic patterns associated with protein-
or RNA-coding genes can be identified by gene finding algorithms, which allow researchers to predict the presence of particular gene products in an organism even before they have been isolated experimentally.[121]
DNA nanotechnology
The DNA structure at left (schematic shown) will self-assemble into the structure visualized by atomic force microscopy at right. DNA nanotechnology is the field which seeks to design nanoscale structures using the molecular recognition properties of DNA molecules. Image from Strong, 2004. [1]
Further information: DNA nanotechnology
DNA nanotechnology uses the unique molecular recognition
properties of DNA and other nucleic acids to create self-assembing
branched DNA complexes with useful properties. DNA is thus used as a
structural material rather than as a carrier of biological information.
This has led to the creation of two-dimensional periodic lattices (both
tile-based as well as using the "DNA origami" method) as well as three-dimensional structures in the shapes of polyhedra. Nanomechanical devices and algorithmic self-assembly have also been demonstrated, and these DNA structures have been used to template the arrangement of other molecules such as gold nanoparticles and streptavidin proteins.
DNA and computation
Further information: DNA computing
DNA was first used in computing to solve a small version of the directed Hamiltonian path problem, an NP-complete problem.[122] DNA computing
is advantageous over electronic computers in power use, space use, and
efficiency, due to its ability to compute in a highly parallel fashion
(see parallel computing). A number of other problems, including simulation of various abstract machines, the boolean satisfiability problem, and the bounded version of the travelling salesman problem, have since been analysed using DNA computing.[123] Due to its compactness, DNA also has a theoretical role in cryptography, where in particular it allows unbreakable one-time pads to be efficiently constructed and used.[124]
History and anthropology
Further information: Phylogenetics and Genetic genealogy
Because DNA collects mutations over time, which are then inherited,
it contains historical information and by comparing DNA sequences,
geneticists can infer the evolutionary history of organisms, their phylogeny.[125] This field of phylogenetics is a powerful tool in evolutionary biology. If DNA sequences within a species are compared, population geneticists can learn the history of particular populations. This can be used in studies ranging from ecological genetics to anthropology; for example, DNA evidence is being used to try to identify the Ten Lost Tribes of Israel.[126][127]
DNA has also been used to look at modern family relationships, such
as establishing family relationships between the descendants of Sally Hemings and Thomas Jefferson.
This usage is closely related to the use of DNA in criminal
investigations detailed above. Indeed, some criminal investigations
have been solved when DNA from crime scenes has matched relatives of
the guilty individual.[128]
