Molecular Basis for

1
Molecular Basis for Relationship between Genotype
and Phenotype
DNA
genotype
DNA sequence
transcription
RNA
translation
amino acid sequence
protein
function
organism
phenotype
2
Molecular Basis for Relationship between Genotype
and Phenotype
DNA
genotype
DNA sequence
transcription
RNA
translation
amino acid sequence
protein
function
organism
phenotype
3
Alternative Splicing Produces Related but
Distinct Protein Isoforms
4
Posttranslational Events
Protein Folding Translational product
(polypeptide) achieves appropriate folding by aid
of chaperone proteins. Modification of Amino
Acids Phosphorylation/dephosphorylation
Ubiquitination Protein Targeting Directing
proteins to specific locations (for example,
nucleus, mitochondria, or cell membrane) is
accomplished by tagging of proteins (signal
sequence for secreted proteins, nuclear
localization sequences for nuclear proteins).
5
Posttranslational Events
Protein Folding Translational product
(polypeptide) achieves appropriate folding by aid
of chaperone proteins. Modification of Amino
Acids Phosphorylation/dephosphorylation
Ubiquitination Protein Targeting Directing
proteins to specific locations (for example,
nucleus, mitochondria, or cell membrane) is
accomplished by tagging of proteins (signal
sequence for secreted proteins, nuclear
localization sequences for nuclear proteins).
6
Phosphorylation and Dephosphorylation of Proteins
Kinases add phosphate groups to hydroxyl groups
of amino acids such as serine and threonine.
Phosphatases remove phosphate groups.
7
Ubiquitinization Targets a Protein for Degradation

• Short-lived proteins are ubiquitinated
• cell-cycle regulators
• damaged proteins

8
Posttranslational Events
Protein Folding Translational product
(polypeptide) achieves appropriate folding by aid
of chaperone proteins. Modification of Amino
Acids Phosphorylation/dephosphorylation
Ubiquitination Protein Targeting Directing
proteins to specific locations (for example,
nucleus, mitochondria, or cell membrane) is
accomplished by tagging of proteins (signal
sequence for secreted proteins, nuclear
localization sequences for nuclear proteins).
9
Signal Sequences Target Proteins for Secretion
Signal sequence at the amino-terminal end of
membrane proteins or secretory proteins are
recognized by factors and receptors that mediate
transmembrane transport. Signal sequence is
cleaved by signal peptidase.
Nuclear localization sequences (NLSs) are located
in interior of proteins such as DNA and RNA
polymerases. They are recognized by nuclear pore
proteins for transport into nucleus.
10
Molecular Basis for Relationship between Genotype
and Phenotype
DNA
genotype
DNA sequence
transcription
RNA
translation
amino acid sequence
protein
function
organism
phenotype
11
Frameshift Mutations and Suppressor Mutations
frameshift mutations insertions or deletions of
nucleotides that cause a shift in the
translational reading frame
suppressor mutations mutations that counteract
or suppress the effects of another mutation
wild-type CAU CAU CAU CAU CAU HIS HIS
HIS HIS HIS
addition of A
deletion of A
CAU ACA UCA UCA UCA U__ HIS THR SER
SER SER .
CAU ACU CAU CAU CAU HIS THR HIS HIS
HIS
deletion of U
addition of G
CAU CAC AUC AUC AU__ HIS HIS ILE
ILE .
CAU CAC GAU CAU CAU HIS HIS ASP HIS
HIS
12
Mutation Levels of Hereditary Change
Gene (Point) Mutation One allele changes to a
different allele. Effects are limited to that
locus.
Chromosome Mutation Changes occur at the
chromosome level. Multi-locus effects are not
unusual.
13
Molecular Basis for Relationship between Genotype
and Phenotype
DNA
genotype
DNA sequence
transcription
RNA
translation
amino acid sequence
protein
function
organism
phenotype
14
Point mutations at the molecular level
Base substitution change in base of nucelotide
pair Base additions insertion of nucleotide
pairs Base deletions deletion of nucleotide
pairs
15
Point mutations at the molecular level
16
Consequences of Point Mutations within Genes
17
Point Mutations Can Alter mRNA Splicing
18
Point Mutations on Gene Products