SHADOW OF DNA Part 6

DNA’s ROLE IN FORENSIC SCIENCE


DNA has been an increasingly important part of
forensic science and crime solving in the last few
decades. Since DNA differs between each
individual, a person can be linked to a crime
based on the genetic information that is found at
a crime scene. This generic information can also
be used as exculpatory evidence to clear an
individual’s name from the list of suspects.
Similar to the use of fingerprints, investigators
collect blood samples as well as saliva, hair and
any skin that may be under a victim’s fingernails.
These samples are then tested for the DNA
information and can also identify a victim to the
relatives in the event that no body can be located.
Once the DNA evidence is in the computer
system, this information can be connected to
crimes in other areas of the country as well. This
is especially useful for similar crimes that occur
at different locations which may or may not be
caused by one person.
DNA can be tested from teeth, fingernails, urine,
mucus, perspiration, and other bodily fluids; this
valuable DNA information can be found on
evidence from decades prior to the investigation.
Environmental factors can affect DNA, so every
piece of DNA that is found cannot always be used
as part of the profile. The tests from the DNA
cannot indicate how long age the suspect was at
the crime scene, it can only determine whether or
not the suspect was there.
Since forensic technology has advanced so much
in recent years, police are reopening cold cases to
further analyze any possible DNA evidence left
over from the original investigation. Not only has
the emerging technology put criminals in jail, but
it has also exonerated many people who had
been serving time for a crime.
DNA Forensics : Information on how forensic
identification works in relation to DNA.
DNA Typing : Information on the basics of DNA
typing.
DNA Profiling : DNA profiling information in
forensic science.
Forensic DNA : Information on the research and
backlogs of forensic DNA.
DNA Use : Information on the use of DNA in the
legal system.

SHADOW OF DNA Part 5

DNA STRUCTURE AND ITS ROLE IN FORENSIC SCIENCE.......


DNA stands for deoxyribonucleic acid and is the
material in most organisms, including humans,
that controls hereditary properties. It is the
building block that is fundamental for the entire
genetic makeup of an individual or being.
Although a small amount of DNA can be found in
the mitochondria, most DNA is found in the cell
nucleus. The same DNA is present in nearly all of
the cells of a person’s body which means that the
DNA in blood cells is the same as the DNA in
saliva and skins cells. Although the DNA is
virtually the same in almost every aspect of a
person, it differs between another person unless
they are identical twins. The long-term
information that is stored in DNA is used to
instruct the functioning and development of living
organisms except for some viruses.
DNA Structure
Each DNA is made of two nucleotides that have
backbones made from phosphate and sugar
groups and are joined together by ester bonds.
The nucleotides are anti-parallel, which means
they run in the opposite direction of each other.
Four types of molecules, called bases, are
attached to each sugar. These bases are:
adenine
thymine
cytosine
guanine
The bases are sequenced along the backbones in
a way that encodes information. Guanine and
adenine are purines, which are the larger of the
two types of bases. The other type of bases is
pyrimidine which consists of cytosine and
thymine.
The information that is encoded is used by use of
the genetic code; this shows the specific
sequence of amino acids within the proteins. The
process of reading this information is called
transcription. DNA is organized within cells as
long structures called chromosomes; when these
chromosomes are duplicated before they are
divided, the process is called DNA replication.

SHADOW OF DNA Part-4

RNA structures
RNA molecules are also polynucleotides with a sugar-phosphate backbone and four kinds of bases. The main differences between RNA and DNA are:

• RNA molecules are single-stranded
• The sugar in RNA is a ribose sugar (as opposed to deoxy-ribose) and has an �OH at the 2' C position highlighted in red in the figure below (DNA sugars have �H at that position)
• Thymine in DNA is replaced by Uracil in RNA. T has a methyl (-CH₃) group instead of the H atom shown in red in U.

The picture shows an ATP molecule (adenosine tri-phosphate) about to be incorporated into an RNA chain with the release of a di-phosphate).
RNA molecules do not have a regular helical structure like DNA. Instead, they can form complicated 3-dimensional structures where the strands can loop back and form intra-strand base-pairs from self-complementary regions along the chain.
DNA structure


RNA structure


There are three classes of RNA molecules:

• messenger RNA (mRNA) which acts as a template for protein synthesis and has the same sequence of bases (read from the 5' to the 3' end) as the DNA strand that has the gene sequence. mRNA can range from ~300 nucleotides to ~7000 nucleotides, depending on the size and the number of proteins that they are coding for.

• transfer RNA (tRNA), one for each triplet codon that codes for a specific amino-acid (the building blocks of proteins). tRNA molecules are covalently attached to the corresponding amino-acid at one end, and at the other end they have a triplet sequence (called the anti-codon) that is complementary to the triplet codon on the mRNA. All tRNA molecules are in the range ~70-90 nucleotides. They have a molecular weight of ~25,000 and have sedimentation constant ~ 4 Svedberg (S) units.

• ribosomal RNA (rRNA) which make up an integral part of the ribosome, the protein synthesis machinery in the cell.

SHADOW OF DNA Part-3

The Three Roles of RNA in Protein Synthesis

Although DNA stores the information for protein synthesis and RNA carries out the instructions encoded in DNA, most biological activities are carried out by proteins. The accurate synthesis of proteins thus is critical to the proper functioning of cells and organisms. We saw in Chapter 3 that the linear order of amino acids in each protein determines its three-dimensional structure and activity. For this reason, assembly of amino acids in their correct order, as encoded in DNA, is the key to production of functional proteins.

Three kinds of RNA molecules perform different but cooperative functions in protein synthesis:-

The three roles of RNA in protein synthesis. Messenger RNA (mRNA) is translated into protein by the joint action of transfer RNA (tRNA) and the ribosome, which is composed of numerous proteins and (more...)

1.

Messenger RNA (mRNA) carries the genetic information copied from DNA in the form of a series of three-base code “words,” each of which specifies a particular amino acid.

2.

Transfer RNA (tRNA) is the key to deciphering the code words in mRNA. Each type of amino acid has its own type of tRNA, which binds it and carries it to the growing end of a polypeptide chain if the next code word on mRNA calls for it. The correct tRNA with its attached amino acid is selected at each step because each specific tRNA molecule contains a three-basesequence that can base-pair with its complementary code word in the mRNA.

3.

Ribosomal RNA (rRNA) associates with a set of proteins to form ribosomes. These complex structures, which physically move along an mRNA molecule, catalyze the assembly of amino acids into protein chains. They also bind tRNAs and various accessory molecules necessary for protein synthesis. Ribosomes are composed of a large and small subunit, each of which contains its own rRNA molecule or molecules.

SHADOW OF DNA part-2

The most common DNA structure in solution is the B-DNA. Under conditions of applied force or twists in the DNA, or under low hydration conditions, it can adopt several helical conformations, referred to as the A-DNA, Z-DNA, S-DNA...


Shown in picture above are three crystallized states of DNA, the A-DNA (left), B-DNA (middle) and Z-DNA (right). The A-form crystallizes under low hydration conditions and is not normally found for DNA in the cell. It is, however, the structure adopted by double-stranded regions in RNA as well as the transient double-helix between DNA and RNA during transcription.  Both A- and B-DNA are right-handed helices whereas Z-DNA is a left-handed helix and is commonly found in regions of DNA that have an alternating purine-pyrimidine (e.g. 5'-CGCGCGCG-3' or 5'-CGCGCATGC-3') sequences. The table below summarizes some of the major differences.
                                    A-DNA                                B-DNA                                Z-DNA
                             Right-handed helix                    Right-handed                      Left-handed
                                Short and broad                     Long and thin                    Longer and thinner
Helix Diameter                25.5A                                  23.7A                                    18.4A
Rise / base-pair                 2.3A                                    3.4A                                      3.8A
Base-pair / helical turn       ~ 11                                    ~ 10                                        ~ 12
Helix pitch                            25A                                    34A                                        47A
Tilt of the bases                    20 deg                               -1 deg                                   -9 deg

The ball-and-stick representation shown above can be misleading because it suggests that there is empty space between the two strands and between the base-pair stacks. Another representation is the filled space representation in which each of the atoms are shown as a ball of radius representative of its Van der waals radius. The picture below shows this view for the 3 DNA structures shown above.

Here, the B-DNA is on the left and the A-DNA is in the middle. The blue and white atoms are the sugar-phosphate backbone atoms, the red are G-C base-pairs and the yellow are A-T base-pairs. The B-DNA picture shows very clearly the 'grooves' in between the backbones that also spiral around the DNA structure; the grooves in B-DNA come in two sizes, the minor groove and the major groove.
A DNA molecule is not a rigid, static structure as x-ray diffraction pictures might suggest, and the crystallographic parameters shown above are average parameters. In reality, each of these structures are under constant thermal fluctuations, which result in local twisting, stretching, bending, and unwinding of the double-strands. Also, certain sequences lead to permanent bends or kinks in the direction of the helix. These local (sequence-specific) fluctuations are essential for the recognition of specific binding sites along the DNA molecule where proteins involved in replication, transcription, regulation of gene expression, or DNA-damage repair can bind. 

SHADOW OF DNA part-1

INTRODUCTION


DNA is usually a double-helix and has two strands running in opposite directions. (There are some examples of viral DNA which are single-stranded). Each chain is a polymer of subunits called nucleotides (hence the namepolynucleotide).
Each strand has a backbone made up of (deoxy-ribose) sugar molecules linked together by phosphate groups. The 3' C of a sugar molecule is connected through a phosphate group to the 5' C of the next sugar. This linkage is also called 3'-5' phosphodiester linkage. All DNA strands are read from the 5' to the 3' end where the 5' end terminates in a phosphate group and the 3' end terminates in a sugar molecule.

Each sugar molecule is covalently linked to one of 4 possible bases (Adenine, Guanine, Cytosine and Thymine). A and G are double-ringed larger molecules (called purines); C and T are single-ringed smaller molecules (called pyrimidines).
In the double-stranded DNA, the two strands run in opposite directions and the bases pair up such that A always pairs with T and G always pairs with C. The A-T base-pair has 2 hydrogen bonds and the G-C base-pair has 3 hydrogen bonds. The G-C interaction is therefore stronger (by about 30%) than A-T, and A-T rich regions of DNA are more prone to thermal fluctuations.



The bases are oriented perpendicular to the helix axis. They are hydrophobic in the direction perpendicular to the plane of the bases (cannot form hydrogen bonds with water). The interaction energy between two bases in a double-helical structure is therefore a combination of hydrogen-bonding between complementary bases, and hydrophobic interactions between the neighboring stacks of base-pairs.