molecular basis for relationship between genotype and phenotype

Molecular Basis forRelationship between Genotype and Phenotype

DNA

RNA

protein

genotype

function

organismphenotype

DNA sequence

amino acidsequence

transcription

translation

Intron Splicing: Conserved Sequences

exons - coding sequences introns - noncoding sequences

Small nuclear ribonucleoprotein particles (snRNPs) recognize consensus splice junction sequence of GU/AG.

snRNPs are complexes of protein and small nuclear RNA (snRNA). Several snRNPs comprise a spliceosome.

Spliceosome directs the removal of introns and joining of exons.

One end of conserved sequence attaches to conserved adenine in the intron.

The “lariat” is released and adjacent exons are joined.

Spliceosome interacts with CTD and attaches to pre-mRNA.

snRNAs in spliceosomes direct alignment of the splice sites.

Spliceosome Assembly and Function

Reactions in Exon Splicing

These self-splicing introns are an example of RNA that can catalyze a reaction.

RNA molecules can act somewhat like enzymes (ribozymes).

In the protozoan Tetrahymena, the primary transcript of an rRNA can excise a 413-nucleotide intron from itself.

Self-Splicing Reaction

What are the similarities? What are the differences?

Transfer of Information in Prokaryotes and Eukaryotes

Colinearity of Gene and Protein

DNA

RNA

protein

genotype

function

organismphenotype

DNA sequence

amino acidsequence

transcription

translation

“The linear sequence of nucleotides in a gene determines the linear sequence of amino acids in a protein.”

Mutant alleles of trpA gene differed in the position of the mutation at the DNA level, which corresponded to position of amino acid substitution in the gene product.

Colinearity of Gene and Protein

Colinearity of mutations and altered amino acids in subunit of tryptophan synthetase from E. coli

C. Yanofsky, 1967. Scientific American

indole-3-glycerol phosphate

Tryptophan Synthetase Activity

indole

glyceraldehyde 3-phosphate

tryptophan

serine

subunit

subunit

Molecular Basis forRelationship between Genotype and Phenotype

DNA

RNA

protein

genotype

function

organismphenotype

DNA sequence

amino acidsequence

transcription

translation

Anticodon of a tRNA molecule recognizes and pairs with an mRNA codon.

tRNA contains modified bases: pseudouridine, methylguanosine, dimethylguanosine, methylinosine, dihydrouridine.

tRNA

Genetic Code

Aminoacyl-tRNA Synthetase Attaches Amino Acid to tRNA

Aminoacyl-tRNA synthetase catalyzes the formation of “charged” tRNA.

There is an aminoacyl-tRNA synthetase for each amino acid.

The carboxyl end of an amino acid is attached to the 3’ end of the tRNA.

Wobble Position

Some tRNA molecules can recognize and pair with more than one specific codon.

Base-pairing between the 3’ base of a codon and 5’ base of an anticodon is not always exact.