chem structure of genes

8/13/2019 Chem Structure of Genes

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DNA

The central dogma of molecular biology

transcription translation

replication

reverse-transcription

replication

RNA protein


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Watson and Crick1953


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DNA is a polynucleotide

(i.e., a polymer of nucleotides)

general structure of a nucleotide

Note labels of

C atoms

deoxyribose, a five-carbon sugar

Purine and pyrimidine bases


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NOMENCLATURE CONVENTIONS

Base Nucleoside Nucleotides(base and sugar) (Nucleoside Phosphates)

Purines:

Adenine (A) Adenosine, deoxyadenosine AMP, dADP, ATP, dATP

Guanine (G) Guanosine, deoxyguanosine GMP, dGDP, GDP, dGTP

Hypoxanthine Inosine (I) IMP

Pyrimidines:

Cytosine (C) Cytidine, deoxycytidine CMP, dCDP, CTP

Uracil (U) Uridine, deoxyuridine UMP, dUDP

Thymine (T) Thymidine Thymidylic acid, dTMP


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Structure of nucleotides in DNA

Nucleoside triphosphates


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Note polarity of chain

Note polarity of chains


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Watson-Crick Base Pairing

AT

Hydrogen bond

GC

Chargaffs Rule

[A+G] = [C+T]

Purines = Pyrimidines

[A] = [T]

[G] = [C]


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Major groove

Minor groove

Other structural featuresof DNA: B-DNA

Structural polymorphism of DNA:B vs. Z-DNA


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Structural polymorphism of DNA:A, B and Z-DNA

What is a chromosome?


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Types of eukaryotic DNA

Protein-coding genes

Solitary genes

Duplicated and diverged genes (functional gene families

and nonfunctional pseudogenes) Tandemly repeated genes encoding rRNA, 5S rRNA, tRNA,

and histones

Repetitive DNA

Simple-sequence repeats

Moderately repeated DNA (mobile DNA elements)

Transposons

Viral retrotransposons

Long interspersed elements (LINES, nonviralretrotransposons)

Short interspersed elements (SINES, nonviralretrotransposons)

Unclassified spacer DNA

DNA vs. RNA

a ribonucleotide

OH

RNA is a polymer of ribonucleotides


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RNA single stranded

consists of four ribonucleotides A,U,G,C

sugar is a ribose forms secondary structure

What is a gene?

(classical) the determinant of an observable trait of an

organism

(molecular) the DNA sequence that determines thechemical structure of a specific polypeptide or RNAmolecule

(molecular) entire nucleic acid sequence necessary forthe synthesis of a functional polypeptide (proteinchain) or functional RNA


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Gene definition caveats

Some genomes are RNA instead of DNA

Some gene products are RNA (tRNA, rRNA,

and others) instead of protein

Some nucleic acid sequences that do not

encode gene products (noncoding regions)

are necessary for production of the geneproduct (RNA or protein)

Reading frame

The genetic code is triplet and non-

overlapping. Example:ggactttggctaagatttgattcctga

Possible reading frames in a sequenceof DNA

3 per strand (therefore, 6 for duplex DNA)


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The protein-coding region

open reading frame (ORF)

The molecular definition of gene includes more thanjust the coding region


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Coding and template strands

Only one strand of DNA serves as a templatefor transcription.

(coding, non-template strand)

(template strand)


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Different genes may be transcribed fromdifferent strands


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Promoter - a critical control site

Nucleotide at which transcription starts isdesignated +1

+1Promoter

Nucleotides with negative and positive

numbers indicate upstream and downstreamnt, respectively.

Region of DNA to which RNA polymerase bindsbefore initiating the transcription of DNA into RNA.


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Functions of a promoter

The promoter determines:

Which strand will serve as a template.

Transcription starting point.

Strength of polymerase binding.

Frequency of polymerase binding.

Coding sequence not continuous

Eukaryote gene structure

majority of nuclear protein coding genes consist mostlyof introns

monocistronic mRNA: encodes a single protein


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(Exon-intron-exon)n structure of various genes

-globin

HGPRT

(HPRT)

total = 1,660 bp; exons = 990 bp

histone

factor VIII

total = 400 bp; exon = 400 bp

total = 42,830 bp; exons = 1263 bp

total = ~186,000 bp; exons = ~9,000 bp

exon intron


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Alternative splicing

Splicing - removal of introns and joining ofexons

mRNA from some genes can be spliced intotwo or more different mRNAs


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Noncoding regions

Intergenic regions

Regulatory regions

RNA polymerase binding site

Transcription factor binding sites

Introns

Polyadenylation [poly(A)] sites

Duplicated genes

Encode closely related (homologous) proteins

Clustered together in genome

Formed by duplication of an ancestral genefollowed by mutation

Five functional genes and two pseudogenes


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Pseudogenes

Nonfunctional copies of genes Formed by duplication of ancestral gene, or

reverse transcription (and integration)

Not expressed due to mutations that producea stop codon (nonsense or frameshift) orprevent mRNA processing, or due to lack of

regulatory sequences

Classes of repetitive DNA

Interspersed (dispersed) repeats (e.g., Alu sequences)

TTAGGGTTAGGGTTAGGGTTAGGG

Tandem repeats (e.g., microsatellites)

GCTGAGG GCTGAGGGCTGAGG


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Repetitive DNA

Moderately repeated DNA Tandemly repeated rRNA, tRNA and histone genes(gene products needed in high amounts)

Large duplicated gene families

Mobile DNA

Simple-sequence DNA

Tandemly repeated short sequences

Found in centromeres and telomeres (and others)

Used in DNA fingerprinting to identify individuals

Bacterial genes

Most do not have introns

Many are organized in operons: contiguousgenes, transcribed as a single polycistronicmRNA, that encode proteins with relatedfunctions; a polycistronic mRNA encodes

several proteins


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Bacterial operon

Next meeting

Survey of techniques for

characterizing genes and genomes

chem structure of genes

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