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Molecular Basis for Relationship between Genotype and Phenotype genotype DNA DNA sequence transcription RNA translation protein function phenotype organism amino acid sequence Molecular Basis for Relationship between Genotype and Phenotype genotype DNA DNA sequence transcription RNA translation protein function phenotype organism amino acid sequence 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 for Relationship between Genotype and Phenotype genotype DNA DNA sequence transcription RNA translation protein function phenotype organism amino acid sequence 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 CAU ACA UCA UCA UCA U__ HIS THR SER SER SER . deletion of U CAU CAC AUC AUC AU__ HIS HIS ILE ILE . deletion of A CAU ACU CAU CAU CAU HIS THR HIS HIS HIS addition of G CAU CAC GAU CAU CAU HIS HIS ASP HIS HIS 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. Molecular Basis for Relationship between Genotype and Phenotype genotype DNA DNA sequence transcription RNA translation protein function phenotype organism amino acid sequence 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 Point mutations at the molecular level Consequences of Point Mutations within Genes Point Mutations Can Alter mRNA Splicing Point Mutations on Gene Products