Genetics exam 2

• There is no such thing as peptidyl transferase; the large ribosomal subunit is said to have peptidyl transferase activity

After Translation: Post-Translational Modification

• Disulfide bridge addition occurs in the eukaryotic lumen of the Rough ER (RER).
• Adding chemical groups to the N-terminus is a common modification.

Chemical Group Examples

• Glycosylation occurs mainly in the Golgi, but sometimes in the ER.
• Acetylation is the most common modification.
• Phosphorylation is carried out by kinases.
• Methylation, Hydroxylation, and Carboxylation.
• Modifications also includes cleavage and addition of amino acids
• Shape modifications are made by chaperones and/or chaperonins.

Proteins and Their Structure

• Most proteins can change shape depending on the cellular environment, substances bound to them, and their inherent nature.
• Inherently disordered proteins (IDPs) are an example of a protein's inherent nature.
• About 25% of mammalian proteins are IDPs.
• Many proteins can moonlight or perform multiple jobs.

Genome

• Genome includes the genes that code for proteins.
• There are about 20,000–25,000 genes in the genome.

Transcriptome

• Transcriptome includes all RNAs, specifically mRNA.
• There are about 250,000 transcriptomes.

Proteome

• Proteome includes all the proteins.
• There are more than 1,000,000 proteomes.
• Alternative splicing can be one of the causes of complexity
• RNA editing can cause complexity
• Post-translational modification can cause complexity

Alternative Splicing

• Multiple mRNAs can be made from the same gene by splicing different exons.
• Different proteins are called isoforms.
• Fibronectin mRNA is present in fibroblasts vs. hepatocytes, but is missing EIIIB and EIIIA.

RNA Editing

• RNA nucleotides are altered after transcription through substitution, addition, or deletion of nucleotides.
• Guide RNA (gRNA) binds to the transcript and causes addition or deletion of bases.

Gene Regulation/Gene Expression Control

• One way of assuring that a gene is more active is by increasing the number of genes available for transcription.

Polytenty and Polyploidy

• Polytenty: endoduplication of DNA without increasing chromosomal number.
• DNA does not separate, and endoduplication occurs by copying within.
• Common in dipterians
• Polyploidy: Possessing 3 or more sets of chromosomes. DNA do not separate. Usually have 3 or more copies of each gene. It increases the chromosome number and can be advantageous if more gene product is needed.
• Sometimes, they may be chosen to be kept

Worked Questions

• Given 2 chromosomes where each weighs 100 pg:
• If a triploid condition arises, the individual will have 3 copies of the chromosomes and the chromosomes will weigh 300 pg.
• If a polyteny situation arises, the individual will have 2 copies of the chromosomes and the chromosomes will weigh 400 pg.

Definitions

• Structural genes code for proteins that are used in metabolism or have structural roles;
• Regulatory genes code for proteins of RNAs that affect gene expression.
• Constitutive genes are constantly expressed, and their protein products encode vital cellular functions that are not regulated
• Cis-acting sequences are sites located 5' from the transcription initiation site.
• Trans-acting factors , typically proteins, bind to the cis-acting sequences to help initiate transcription.
• DNA-binding proteins are involved in most regulation and either promote or inhibit transcription.
• Enhancers are regulatory sequences on DNA to which proteins bind and enhance transcription; enhancers may be located upstream or downstream from a gene, or even in the intron of the gene.
• Silencers are regulatory sequences on DNA to which proteins bind and inhibit, or decrease transcription.
• The structural gene example is hexokinase.
• Regulatory genes include enhancer proteins and transcription factors.

Motifs

• Helix-turn-helix binds to the major groove.
• Zinc-finger binds to the major groove.
• Leucine-zipper binds to two adjacent major grooves.

Multiple Methods of Controlling Gene Expression

• Controlling gene expression can occur at multiple steps:
• DNA (genome)
• Transcriptional control
• Premature mRNA (transcriptome) - Post-transcriptional control processing
  • RNA Editing
  • Alternative Splicing
  • Polyadenylation
  • mRNA (transcriptome)
  • Translational & degradation control
  • Translation (proteome) - Protein
    • Post-Translational Modifications
    • Degradation
• Eukaryotes can make mature mRNA slowly or destroy mRNA for controlling mature mRNA.