Molecular Basis forRelationship between Genotype and Phenotype

DNA

RNA

protein

genotype

function

organismphenotype

DNA sequence

amino acidsequence

transcription

translation

Molecular Basis forRelationship between Genotype and Phenotype

DNA

RNA

protein

genotype

function

organismphenotype

DNA sequence

amino acidsequence

transcription

translation

Alternative Splicing Produces Related but Distinct Protein Isoforms

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).

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).

Phosphorylation and Dephosphorylation of Proteins

Kinases add phosphate groups to hydroxyl groups of amino acids such as serine and threonine.

Phosphatases remove phosphate groups.

Ubiquitinization Targets a Protein for Degradation

Short-lived proteins are ubiquitinated:

• cell-cycle regulators

• damaged proteins

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).

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.

Molecular Basis forRelationship between Genotype and Phenotype

DNA

RNA

protein

genotype

function

organismphenotype

DNA sequence

amino acidsequence

transcription

translation

wild-type

CAU CAU CAU CAU CAUHIS HIS HIS HIS HIS

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

CAU ACA UCA UCA UCA U__

HIS THR SER SER SER .

addition of A

CAU ACU CAU CAU CAUHIS THR HIS HIS HIS

deletion of A

CAU CAC AUC AUC AU__

HIS HIS ILE ILE .

deletion of U

CAU CAC GAU CAU CAUHIS HIS ASP HIS HIS

addition of G

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.

Mutation: Levels of Hereditary Change

Molecular Basis forRelationship between Genotype and Phenotype

DNA

RNA

protein

genotype

function

organismphenotype

DNA sequence

amino acidsequence

transcription

translation

Base substitution: change in base of nucelotide pair

Base additions: insertion of nucleotide pairs

Base deletions: deletion of nucleotide pairs

Point mutations at the molecular level

Point mutations at the molecular level

Consequences of Point Mutations within Genes

Point Mutations Can Alter mRNA Splicing

Point Mutations on Gene Products