Chapter 1, Genes, Genetic Codes and Mutation

 

Chapter1, Genes, Genetic Codes and Mutation

 

NUCLEOTIDE SEQUENCES

 

DNA - two complementary strands

4 kinds of nucleotides - 2 purines [R] (adenine [A], guanine [G]), 2 pyrimidines [Y] (thymine [T], cytosine[C])

A=T weak bond, G≡C strong bond, canonical base pairs

5' - upstream, 3' - downstream

heavy strand - contains many purines, light strand - contains many pyrimidines

RNA - single- or double-stranded

Uracil [U] instead of thymine [T]

A, T, G, C, U - standard nucleotides

units - base pairs (bp), kilobases (Kb), megabases(Mb)

 

GENOMES AND DNA REPLICATION

 

Genome - the entire complement of genetic material carried out by an individual

Genic DNA - contains genes

Nongenic DNA - does not contain genes

Transcriptome - the entire set of transcribed sequences produced by the genome

Proteome - the entire set of proteins encoded by the genome

Semiconservative replication

Replication bubble - origin of replication

Replication folks - where replication proceeds

Leading strand - template for a continuosly synthesiszed daugher strand

Lagging strand - replicated with Okazaki fragments, which are subsequetly ligated

 

GENES AND GENE STRUCTURE

 

Gene - a sequence of genomic DNA or RNA that is essential for a specific function.

1. Protein-coding genes

2. RNA-specifying genes

3. Untranscribed genes

1 & 2 == structural / productive genes

Transcription - the synthesis of a complementary RNA molecule on a DNA template

RNA pol I   - rRNA gene

RNA pol II  - protein-coding gene

RNA pol III - tRNA gene

 

Protein-coding genes

 

5' and 3' flanking regions

Precursor messenger RNA (pre-mRNA) - the transcribed RNA

Heterogenous nuclear RNA (hnRNA) - the pre-mRNAs in the nucleus

Antisense strand - the DNA strand from whcih the pre-mRNA is transcribed

Sense strand- the untranscribed complementary strand identical with the pre-mRNA

Transcription initiation site

Transcription termination site

Polyadenylation site

Introns/Exons

Protein coding exons (coding regions)

5' and 3' untranslated regions (UTRs)

Non-self-splicing (spliceosomal) introns - introns that are transcribed by RNA pol II

Self-splicing introns - cleaved out without the help of exogenous gene products

Splicing sites (junctions) - donor and acceptor sites

GT-AG rule

 

RNA-specifying genes

They are transcribed into RNA but are not translated into proteins

 

Posttranscriptional modifications of RNA

RNA editing - production of an RNA molecule that is not complementary to the DNA sequence from which it has been transcribed

Cryptogene - RNA editing is extensively occured so RNA bearing little resemblance to the DNA sequence

 

Untranscribed genes

Replicator genes -  specifying the sites for initiation and termination of DNA replication

Recombinator genes - provide specific recognition sites for the recombination enzymes during meiosis

Telomeric sequences - short, repetitive seq at the end of many eukaryotic chromosomes, work as protective cap

Segregator genes - provide specific sites for attachment of the chromosomes to the spindle machinery during meiotic and mitotic segration

Attachment sites

Constructional sites

 

Pseudogenes

Pseudogenes (prefix Ψ, suffix P) - a nongenic DNA segment due to defects

 

AMINO ACIDS

 

20 AAs

-NH2 (amine) group, -COOH (carboxyl) group, α carbon, -H, -R group (side chain)

 

PROTEINS

 

Peptide bond

N terminus

C terminus

Primary structure - linear arrangement

Secondary structure - folding, α helix, β-pleated sheet, random coil

Tertiary structure - spatial arrangement, subunit

Quaternary structure - spatial arrangement of subunits

Prosthetic groups - nonprotein components

Holoprotein - protein/prosthetic group complex

Apoprotein - protein w/o prosthetic group

 

TRANSLATION AND GENETIC CODES

 

tRNA - has anticodon

aminoacyl-tRNA synthetases

Translation

Codon - triplets of nucleotides, initiation codon / stop codon

Reading frame

Release factors - recognize stop codon and terminate the translation process

Genetic code - universal, 61 sense codons + 3 stop codons, unambiguous

Degenerate code - most AAs are encoded by more than 1 codon

Synonymous codons - different codons specifying the same AA

Codon family - Synonymous codons that differ from each other at 3rd position only

Absent codon - codons never appear in protein-coding genes

Unassigned codon - no appropriate tRNA that can pair

 

MUTATION

 

Point mutation / Segmental mutation

 

Substitution mutatations

Transitions - A <-> G (purines), C <-> T (pyrimidines), 4 types

Transversion - R <-> Y, 8 types

Synonymous - no change in AAs <- silent mutation

Nonsynonymous - a change in AAs, replacement <- AA-altering mutations

1. missense mutation - different AAs

2. nonsense mutation - sense codon -> stop codon

Pretermination codons

 

Recombination

Crossing over (reciprocal recombination) - even exchange of homologous seqs

Gene conversion (nonreciprocal recombination) - uneven replacement of seqs

Holliday structure (or junction)

Heteroduplexes - the formation of streches of mismatched dsDNA

Homologous recombination

Site-specific recombination - the exchange of seq by another one that bears no similarity

 

Deletion and insertions

Unequal crossing over

Intrastrand deletion

Replication slippage (slipped-strand mispairing)

Indels

Frameshift mutation

 

Inversions

1. chromosome breakage and rejoining

2. intrachromosomal crossing over between two homologous segments that are oriented opposite directions

 

Mutation rates

Estimated indirectly from the rate of substitution in pesudogenes

Mutation rate varies enormously with genomic region

 

Spatial distribution of mutations

Hotspots - regions more prone to mutate, e.g. 5'-CG-3' (CpG) -> 5'-TG-3'

 

Patterns of mutation

The direction of mutation is nonrandom

Transtions occur more frequently than transversions

 

Are mutations random?

Do NOT occur at random with respect to genomic location

NOR do all types of mutations occur with equal frequency

Mutation is RANDOM in respect to their effect on the FITNESS of the organism carrying them