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Genome
 Genome is the complete set of genetic information of a cell or an organism in
particular, the complete sequence of DNA/RNA that carries this information.
 In diploid organisms, it refers to the haploid set of chromosomes present in a cell.
 Depending on its localization, genome may be nuclear or organellar.
 Organellar genomes are again of two types: mitochondrial and chloroplast genome.
 Genome size of organisms differs significantly between different species. The size of
the genome governs the size and complexity of an organism. However, many small
sized organisms, in fact have bigger genomes than their larger counterparts.

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Genome

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Genome
The genome contains all the genes present in the nucleus of a cell. Gene
varies in size from a few hundred DNA/RNA bases to more than few
thousand bases.
 The haploid set of chromosome contains the total genome of the
organism.
 The bacterium Mycoplasma genitalium has a small genome size of 0.58Mb
and the plant Triticum aestivim has a large genome size of 16000Mb. The
genome size in human is 3200Mb.

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Genome

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Role of genes within cells
Genes contain the instructions for each cell to make proteins and RNAs.
Genes are made up of DNA fragments.
Within the cell the DNA performs two tasks:
 Act as information repository including instructions in making the
component molecules of the cells.
 Pass on the information to the next generation.
 The mere presence of DNA does not implicate a cell to be alive and
functional. Mammalian red blood cells (RBCs) discard nucleus during
developmental process and thus lacks DNA in mature state.

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Role of genes within cells
Genes are transcribed to RNA which are processed to various
forms like mRNA, tRNA, rRNA etc. mRNA are translated to
proteins depending on the regulatory signals. tRNA and rRNA
serve as the components of translational machinery.
New functions of RNA are also being discovered like regulatory
(miRNA, siRNA etc) and catalytic (ribozymes) functions.

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Gene expression

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Gene expression
1- Access to gene:
Genes are inaccessible as they are buried deep within the highly
packaged chromosomes. The initial step involves a preparative
process that opens the chromatin structure and positions of the
nucleosome in the region of genome containing active genes.
Events involved in gene expression

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Gene expression
2-Formation of transcription initiation complex:
involves the assembly of a set of proteins into a complex that copy
DNA into RNA. This is a highly regulated process as the
transcription initiation complex must be constructed at the precise
position in the genome, adjacent to active genes to form a RNA
copy.
Events involved in gene expression

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Gene expression
Events involved in gene expression

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Gene expression
3- RNA Synthesis
involves the transcription of a gene into RNA molecule and it
occurs in the nucleus.
Events involved in gene expression

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Gene expression
4- RNA Processing
comprises of post transcriptional modification/alterations of the RNA
molecule and its chemical structure required for the RNA to be translated
into protein or non-coding RNA (rRNA, tRNA, miRNA). RNA splicing
(deletion of introns and combination of exons), 5’ capping, polyadenylation
etc are commonly occurred RNA processing steps in eukaryotes. However,
prokaryotic organisms do not have a well developed RNA processing
mechinary.
Events involved in gene expression

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Gene expression
5- Degradation of RNA
is the controlled turnover of RNA molecules and should not be
viewed simply as a mean of getting rid of unwanted RNAs. It
determines the makeup of the transcriptome and is considered as
an important step in genome expression. Different ribonucleases
(RNases) plays the prime role in this process and multiple
cofactors like small RNA (siRNA, miRNA etc), molecular
cheparons (Lsm1-7, Lsm2-8, Hfq etc) regulate this process.
Events involved in gene expression

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Gene expression
6- Protein synthesis
is initiated after the assembly of the translation initiation complex
near the 5’ termini of a mRNA molecule. It involves translation of
RNA molecules into proteins.
Events involved in gene expression

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Gene expression
7- Protein folding and protein processing
may occur together after protein synthesis. Post translation events
like folding involve the protein attaining its correct three
dimensional configuration. Processing (phosphorylation,
glycosylation, carboxylation etc.) involves the modification of the
protein by addition of chemical groups and removal of one or more
functional units of the protein.
Events involved in gene expression

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Gene expression
1- Constitutive expression:
Housekeeping genes are essential and necessary for sustaining life,
and are therefore continuously expressed. gapdh (glyceraldehydes
3 phosphate dehydrogenase), sdha (succinate dehydrogenase) etc
are human housekeeping genes which are expressed throughout
the development.
Types of gene expression

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Gene expression
2- Induction and repression:
The expression levels of some genes fluctuate in response to
external signals. Also, under a certain situation, some genes show
higher expression level, while others show lower expression levels.
The former is called induced expression and the latter is called
repressed expression.
Types of gene expression

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A. Codons
 Codons are presented in the messenger RNA (mRNA) language of
adenine (A), guanine (G), cytosine (C), and uracil (U).
 Their nucleotide sequences are always written from the 5′ end to
the 3′ end.
 The four nucleotide bases are used to produce the three-base
codons. There are, therefore, 64 different combinations of bases

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A. Codons
How to translate a codon

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A. Codons
 This table (or “dictionary”) can be used to translate any codon
sequence and, thus, to determine which amino acids are coded for
by an mRNA sequence.

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A. Codons
Termination (“stop” or “nonsense”) codons
Three of the codons, UAG, UGA, and UAA, do not code
for amino acids but rather are termination codons.
When one of these codons appears in an mRNA
sequence, it signals that the synthesis of the protein
coded for by that mRNA is complete.

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A. Codons
Termination (“stop” or “nonsense”) codons

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A. Codons
Characteristics of the genetic code
1. Specificity: The genetic code is specific (unambiguous), that is, a particular
codon always codes for the same amino acid.
2. Universality:
The genetic code is virtually universal, that is, the specificity of the
genetic code has been conserved from very early stages of
evolution. (Note: An exception occurs in mitochondria, in which a
few codons have meanings different.

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A. Codons
Characteristics of the genetic code
3. Degeneracy:
The genetic code is degenerate (sometimes called redundant). Although
each codon corresponds to a single amino acid, a given amino acid may
have more than one triplet coding for it. For example, arginine is
specified by six different codons
4. Nonoverlapping
and commaless
The genetic code is nonoverlapping and commaless, that
is, the code is read from a fixed starting point as a
continuous sequence of bases, taken three at a time. For
example, ABCDEFGHIJKL is read as ABC/DEF/GHI/JKL
without any “punctuation” between the codons.

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A. Codons
Consequences of altering the nucleotide sequence
Changing a single nucleotide base on the mRNA chain (a “point mutation”)
can lead to any one of three results:
1. Silent mutation: The codon containing the changed base
may code for the same amino acid. For
example, if the serine codon UCA is given
a different third base “U” to become UCU,
it still codes for serine. This is termed a
“silent” mutation.

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A. Codons
Consequences of altering the nucleotide sequence
Changing a single nucleotide base on the mRNA chain (a “point mutation”)
can lead to any one of three results:
2. Missense mutation:
The codon containing the changed base may
code for a different amino acid. For example,
if the serine codon UCA is given a different
first base “C” to become CCA, it will code for
a different amino acid, in this case, proline.
The substitution of an incorrect amino acid is
called a “missense” mutation.

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A. Codons
Consequences of altering the nucleotide sequence
Changing a single nucleotide base on the mRNA chain (a “point mutation”)
can lead to any one of three results:
3. Nonsense mutation:
The codon containing the changed base may
become a termination codon. For example, if
the serine codon UCA is given a different
second base “A” to become UAA, the new
codon causes termination of translation at
that point and the production of a shortened
(truncated) protein. The creation of a
termination codon at an inappropriate place
is called a “nonsense” mutation.

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A. Codons
Other mutations
 Occasionally, a sequence of three bases that is
repeated in tandem will become amplified in number
so that too many copies of the triplet occur.
 If this occurs within the coding region of a gene, the protein
will contain many extra copies of one amino acid. For
example, amplification of the CAG codon leads to the
insertion of many extra glutamine residues in the Huntington
protein, causing the neurodegenerative disorder, Huntington
disease.
a. Trinucleotide repeat expansion:

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A. Codons
Other mutations
 The additional glutamines result in unstable proteins
that cause the accumulation of protein aggregates. If
the trinucleotide repeat expansion occurs in the
untranslated portion of a gene, the result can be a
decrease in the amount of protein produced as seen,
for example, in fragile X syndrome and myotonic
dystrophy.
a. Trinucleotide repeat expansion:

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A. Codons
Other mutations
 Mutations at splice sites can alter the way in which
introns are removed from the pre-mRNA molecules,
 producing aberrant proteins.
b. Splice site mutations:

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A. Codons
Other mutations
If one or two nucleotides are either deleted
from or added to the coding region of a
message sequence, a frame-shift mutation
occurs and the reading frame is altered. This
can result in a product with a radically different
amino acid sequence or a truncated product
due to the creation of a termination codon.
c. Frame-shift mutations:

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A. Codons
Other mutations
If three nucleotides are added, a new amino acid is
added to the peptide, or if three nucleotides are
deleted, an amino acid is lost. In these instances, the
reading frame is not affected. Loss of three nucleotides
maintains the reading frame but can result in serious
pathology.
c. Frame-shift mutations:

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A. Codons
Other mutations
For example, cystic fibrosis (CF), a hereditary
disease that primarily affects the pulmonary
and digestive systems, is most commonly
caused by a deletion of three nucleotides
from the coding region of a gene, resulting in
the loss of phenylalanine at the 508th
position (ΔF508) in the protein encoded by
that gene. This ΔF508 mutation prevents
normal folding of the CF transmembrane
conductance regulator (CFTR) protein
c. Frame-shift mutations: