genes, genomes seminar of molecular and cell biology markéta dostalíková
TRANSCRIPT
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Genes, genomes
Seminar of molecular and cell biology
Markéta Dostalíková
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Genome
• complete set of information in an organism´s DNA
• human genome– nuclear DNA – linear dsDNA
• 25 000 genes
– mitochondrial - circular dsDNA• 37 genes
– 13 genes encode for proteins (respiration complex – oxidative fosforylation)
– 24 genes encode for 22 tRNA and 2 rRNA
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Gene
• Short strech of DNA encoding a single RNA or a single protein and adjacent sequences that are involved in gene regulation (they are transcribed, but not translated)
• Exon - transcribed into RNA and codes for the amino acid sequence of part of a protein
• Intron - transcribed into RNA, excised by RNA splicing to produce mRNA, does not code for protein
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DNA
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DNA molecule
• 4 types of nucleotides: A,G,C,T• Base,sugar, phosphate
• Hydrogen bonds• Phosphodiester bonds
• 2 polynucleotide chains• Double helix
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Bases
DNA : A, G, C, TRNA : A, G, C, U
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Sugars
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The Formation of DNA
Base + Sugar = Nucleoside– the 1´ carbon of pentose is attached to
nitrogen 1 of pyrymidine or nitrogen 9 of purine
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The Formation of DNA
Base + Sugar + Phosphate = Nucleotide– phosphate is attached to
the 5´-carbon of the pentose ring
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►deoxyribonukleotides – basic structure of DNA
dAMP = deoxyadenosinmonophosphate dATP = deoxyadenosintriphosphate
dNTP
nukleoside(eg. deoxyadenosin)
{
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The other functions of nucleotides
Energy carriers, chemical groups carriers Specific regulators
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The Formation of DNA
Nucleotides join together to form nucleic acid • The hydroxyl group attached to the 3´-pentose carbon of one
nucleotide forms an ester bond with the phosphate of another molecule, eliminating a water molecule
• The link between nucleotides is known as a phosphodiester bond
• Thus, one end of a DNA strand has a sugar residue in which the 5´-carbon is not linked to another sugar residue (the 5´end)
• Whereas at the other end the 3´carbon lacks a phosphordiester bond (the 3´end)
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3’
5’
3’
5’
Po
larity of D
NA
strand
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DNA Structure• The double helical structure of DNA was proposed by Watson and
Crick (1950)• The DNA helix
– The „backbone“ on the outside of the helix consists of alternating sugars and phosphates
– The bases are attached to the sugars and form the „rungs“ of the helix
• The strands are – anti-parallel
• their 5´,3´-phosphordiester links run in opposite directions– complementary
• because of base pairing the chains complement each other
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video
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DNA is usually found in the structure of right-handed double helix of complementary and antiparallel strands
Minor groove
Major groove
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Nucleid acid are polymers of nucleotids. Double-stranded DNA containing deoxyribose can have several conformations
A - DNA Z - DNA
B - DNA
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RNA
can have (3D) conformation because of the intramolecular base-pairing (A-U, G-C)
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Modifications of DNA
• methylation of cytosin
• CpG islands, in promotores, in non-coding regions
• they are involved in the gene imprinting, condensation of X chromosom
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The elementary structural unit of DNA is nucleosome
Histons: H2A, H2B, H3, H4 are present in nucleosome core (each twice). This protein - octamer - scaffold and DNA altogether form nucleosome
The lenght of DNA from one nucleosome to another is 200 bpcca 150 bases pairs is wounded around nucleosome
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Composition of nucleosome
Histons are very conservative proteins containing so call histon fold and long N-ends
Octamer of histons composes from tetramers H3/H4 and two dimers H2A/B
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Nucleosome is dynamic structure
Dynamics of nucleosome condensing and releasing is regulated by other proteins
Other various types of histones can be found in some specific nucleosomes and sequences
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Higher level of chromatin organisation – „solenoid“, 30 nm fiber
Nucleosomes are bound together by H1 activity and activity of N- ends, e.g. H4 free ends
Nucleosome beads on DNA wire
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10 000 fold condensated DNA form mitotic...
...chromosome
Stick structure is in next step condensated by group of proteins - condensins
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Organization of DNA into chromosomesEukaryotic chromosomes contain one linear dsDNADNA associates with histons and creates chromatin
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Chromatin remodeling complexes
Modification of chromatin
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Modification of histons: acetylation, methylation, fosphorylation
Modification of chromatin
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Histon code
In addition to genetic code there is also „histon code“ – next level of genome information realization
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Histon code
Modificated histons are bound to other types of proteins - system of readers and writers
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DNA and histon modifications take place in epigenetic regulation of gene expression
Genetic vs epigenetic information and heredity
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Genetic information
• nearly all information that is realized by cell is in DNA
• information concerning the structure and functioning of cell
• It is carried through generations
• It must be changeable but not too much (lasting and stable
enough vs capability of changing during evolution)
• Genom is complete set of DNA (and thus information)
• Genophore: carrier of genetic information
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Genes• Gene: sequence of nucleid acid which encodes a single polypeptide
chain (protein) or a single RNA chain (rRNA, tRNA)• Eukaryotic and prokaryotic genes differs in many features
(monocistrons, introns)• Regulatory regions of genes – promotors; enhancers• Repetitive sequences: are used for identification • Mobil elementes (transposons): spread in genom• Pseudogenes
Gene locus
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35
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Repetitive sequences are used for identification
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Seqences in DNA:
• Encode aminoacids – proteins (mRNA)• Encode RNA as a final product
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Genetic codeGenetic code – a rule by which certain sequence of bases
determines relevant amino acid
tripletive, universal, redundant
Three bases code one amino acid = triplet = codon
20 coded amino acids
4 bases (A, G, C, T) → 64 (43) combination of triplets (codons)
initiation codon is also a codone for methionin
3 triplets function as stop codons 3 possibilities of reading of the sequence of triplets: reading frames
38
Some aminoacids can be encoded by one codon (methionine, tryptophan) some by six codons (leucine, serine, arginine)
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Task
AGUGAAAUGAUUAAUGCAAGGUGAGGGGAGAACGAGUGAUAA
Tyrosine - Y
Tryptofan - W
Glutamine - Q
Arginine - R
Asparagine - N
Lysine - K
Aspartic acid - D
Glutamic acid - E
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Frameshift
Deletion or addition of DNA sequences– They may arise as a result of unequal crossing over during
meiosis, or spontaneous breakage of chromosomes
• For example, deletion of a single base will alter remaining
amino acid sequence
• Duchenne muscular dystrophy (deletion and alteration of
reading frame)
• Becker muscular dystrophy (deletion but not alteration of
reading frame)
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Expansion of trinucleotide repeats
expansion of a sequence of DNA that contains a series of repeated
nucleotide triplets
– In diseases identified so far the repetitive sequence is present in
the gene of normal individuals, but is expanded up to a 1000-fold
in the gene of affected patients
– Myotonic dystrophy – CAG repetition, progressive muscle
weakness
– Huntington‘s disease – progressive dementia and involuntary
movements, in middle age
– Fragile X syndrome – X chromosome linked mental retardation
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Task
To find this nucleotide sequence on web site
gcccgagagaccatgcagaggtcgcctctggaaaaggccagcgttgtctccaaacttttt
http://blast.st-va.ncbi.nlm.nih.gov/Blast.cgi?CMD=Web&PAGE_TYPE=BlastHome