- Genes can be structural or regulatory, with regulatory genes controlling the expression of other genes. - Homeotic genes control embryonic development and malfunctions can result in body parts appearing in abnormal locations. - Gene expression involves transcription of DNA into mRNA, which is then translated into proteins. Regulatory elements and splicing modify gene transcripts.

1. Genes in Action

2. Gene Function Structural genes Become part of the structure & functioning of an organism Regulatory genes Control the action of other genes ie. “switch genes on or off” Or control rate of production of proteins Can switch genes on or off in one of two ways

3. Two types of gene regulation Regulatory genes may code for a DNA-binding protein These have a positively charged binding site that will enable it to bind to DNA They will bind to a region near a gene and directly turn it on or off Regulatory genes may code for a signalling protein This will bind to a receptor on the cell membrane Genes will be turned on or off via signal transduction

4. Homeotic Genes “Master genes” that control embryonic development in insects and vertebrates. A malfunctioning homeotic gene in flies may result in wings, legs, antennae and halteres being absent, or appearing in places that they should not.

5. Homeotic Genes In humans, homeotic genes fall in to 4 groups (Hox A,B,C & D). These encompas 39 genes spread over 4 chromosomes Malfunction of HOXC8 results in an extra pair of ribs Malfunction of HOXD13 results in an extra digit between digits 3 & 4 (often fused)

6. Gene Structure The arrangement of base pairs (c) in a piece of double stranded DNA (d) will determine many things, such as the coding and non-coding portions of DNA (a), and the length of a gene (b). Thus many representations of the same strand required.

7. Gene Structure Enzymes need to know when to start and stop reading a section of DNA. If the base pairs were a sentence, regulatory genes may be likened to capital letters and full stops. 5’ 3’ 3’ 5’ Regulatory gene START STOP Promoter region Terminator region

8. Gene Expression Our DNA is like the master plan for building an organism Genes are specific instructions on how to build one tiny part of the entire organism. Genes are located on the DNA, in the nucleus of our cells The mechanisms for making the products for which these genes code are in the cytoplasm How does the message get out of the nucleus and in to the cytoplasm?

9. Gene Expression In order to be expressed, DNA must be transcribed in to mRNA. A C A T A G G C T T G T A T C C G A

10. Transcription After the complimentary strand is unzipped, the RNA is written against the template strand of DNA A C A T A G G C T U G U A U C C G A 1 2

11. Transcription: step-by-step The enzyme RNA polymerase attaches to the DNA in the upstream (3’) region of the template strand on the promoter sequence. The double-stranded DNA helix unwinds As RNA polymerase moves down the strand, complimentary RNA bases are put down in a 5’ to 3’ direction. A methylated cap is added to the 5’ end of the mRNA The transcribed portion of the helix recoils once it has provided a template for the mRNA bases

12. Transcription: continued Once RNA polymerase reaches the terminator sequence a hairpin loop forms in the mRNA, causing it to be released Poly-A polymerase cleaves the end of the mRNA and synthesises a poly-A tail (adenine bases and proteins). A single stranded molecule called pre-messenger RNA (pre-mRNA) is produced

13. Post-transcription modification The DNA in Eukaryotic genes is made up of ... Introns (non-coding sequences) Exons (coding sequences) Prokaryotic DNA does not contain introns The entire gene is copied during transcription, so it is necessary to the spice out the introns Exon Exon Exon Intron Intron

14. Post-transcription modification Introns are removed by a spliceosome, which is made up of a bundle of protein factors called snerps (snRNP) The introns are coiled in to a shape called a lariat and released The remaining exons are then joined together.

15. One gene, multiple products Research reveals that a single gene is able to make a different product at different stages of development Also, a single gene can make one type of product in one type of tissue and a different product in another type of tissue tissue How is this possible? The human genome contains approx. 25,000 genes Yet there are approx. 120,000 recognised protein-coding mRNA sequences. How is this possible?

16. Alternative splicing of pre-mRNA A) Intron retention The final product can look quite different if not all introns are spliced out B) Exon juggling Exons can be recombined in a anumber of different combinations

17. Translation The mature mRNA moves out of the nucleus, through a nuclear pore, in to the cytoplasm Ribosome assembles around mRNA and sequence of bases is read in blocks of 3 bases known as triplets ( = 1 codon) A transfer RNA (tRNA) molecule with the complementary anticodon is brought in and attaches to the mRNA The AUG triplet is the “start” codon

19. Codons with corres-ponding amino acids The genetic code is universal 99.9% of species use the same triplet code for the same amino acid

21. Prokaryotes vs Eukaryotes Where transcription / translation occurs Eukaryotes: nucleus then cyctoplasm Prokaryotes: cytoplasm Speed at which it occurs Slower in Eukaryotes due to necessity to move out to cytoplasm as well as time required to splice mRNA Life span of mRNA Prokaryotes: a few minutes Eukaryotes: hours/days to allow time for p/t modification Ribosomes Eukaryotic ribosomes are larger and have a different rRNA to protein ratio

23. Gene regulation in Prokaryotes CASE STUDY: THE LAC OPERON Bacteria have groups of genes that are controlled together and are turned on/off as required The LAC operon is a group of genes that produce the enzymes required to preak down lactose to glucose and galactose The bacterium only wants to produce these enzymes when lactose is present.

24. The LAC Operon Usually a repressor protein (produced by LAC regulatory gene) sits on the controlling region When lactose enters the cell it binds to the repressor, and the repressor releases from the DNA The LAC genes will now start transcribing mRNA, which will enter a ribosome and produce the 3 enzymes required for lactose metabolism When concentration of lactose in the cell decreases, the lactose is released from the repressor and it returns to inhibiting the operon

25. Not all genes produce proteins Instead of mRNA, genes can also be transcribed as: tRNA: then move out in to the cytoplasm as a transfer molecule rRNA: then move in to the cytoplasm to form part of a ribosome The nucleolus is a region in the nucleus where rRNA is transcribed and stored until required

26. Mitochondrial DNA In Eukaryotes, mitochondrial DNA (mtDNA) is a double-stranded circular molecule In humans, it encompasses only 16,568 base pairs and 37 genes in total. Apart from the genes coding for tRNA and rRNA, the rest are involved in cellular respiration. Mitochondrial DNA is inherited entirely along maternal lines.