Gene Expression Through Time and Tissue

2. Gene Expression Through Time and Tissue • Changes in gene expression may occur over time and in different cell types • This may occur at the molecular, tissue, or organ/gland level • Epigenetic changes • - Changes to the chemical groups that associate with DNA that are transmitted to daughter cells after cell division

3. Hemoglobin Adult hemoglobin has four globular polypeptide chains - Two alpha (a) chains = 141 amino acids - Encoded on chromosome 11 - Two beta (b) chains = 146 amino acids - Encoded on chromosome 16

4. Hemoglobin Each globin surrounds an iron-containing heme group Figure 11.1

5. Globin Chain Switching Subunits change in response to oxygen levels Subunit makeup varies over lifetime - Embryo = Two epsilon (e) + two zeta (z) - Fetus = Two gamma (g) + two alpha (a) - Adult = Two beta (b) + two alpha (a) - The adult type is about 99% of hemoglobins by four years of age

6. Globin Chain Switching Figure 11.2

7. Changing Gene Expression in Blood Plasma Blood plasma contains about 40,000 different types of proteins Changing conditions cause a change in the protein profile of the plasma Stem cell biology is shedding light on how genes are turned on and off

8. Pancreas The pancreas is a dual gland - Exocrine part releases digestive enzymes into ducts - Endocrine part secretes polypeptide hormones directly into the bloodstream

9. Pancreas Differential gene expression produces either endocrine or exocrine cells If transcription factor pdx-1 is activated, some progenitor cells follow the exocrine pathway Other progenitor cells respond to different signals and yield daughter cells that follow the endocrine pathway

10. Figure 11.3 Figure 11.4

11. Proteomics Proteomics tracks all proteins made in a cell, tissue, gland, organ or entire body Proteins can be charted based on the relative abundance of each class at different stages of development There are fourteen categories of proteins - Including the immunoglobulins, which are activated after birth

12. Figure 11.4 Figure 11.5

13. Control of Gene Expression A protein-encoding gene contains some controls over its own expression level - Promoter sequence (mutations) - Extra copies of gene Much of the control of gene expression occurs in two general processes 1) Chromatin remodeling = “On/off” switch 2) microRNAs = “Dimmer” switch

14. Chromatin Remodeling Histones play major role in gene expression - Expose DNA when and where it is to be transcribed and shield it when it is to be silenced The three major types of small molecules that bind to histones are: - Acetyl group - Methyl groups - Phosphate groups

15. Chromatin Remodeling Figure 11.5

16. Acetyl binding can subtly shift histone interactions in a way that eases transcription Figure 11.6

17. Chromatin Remodeling

18. MicroRNAs belong to a class of molecules called noncoding RNAs They are 21-22 bases long The human genome has about 1,000 distinct microRNAs that regulate at least 1/3rd of the protein-encoding genes When a microRNA binds to a “target” mRNA, it prevents translation MicroRNAs

19. Figure 11.7

20. Cancer provides a practical application of microRNAs because certain microRNAs are more or less abundant in cancer cells than in healthy ones A related technology is called RNA interference (RNAi) - Small synthetic, double-stranded RNA molecules are introduced into selected cells to block gene expression MicroRNAs

21. RNA Interference Animation Please note that due to differing operating systems, some animations will not appear until the presentation is viewed in Presentation Mode (Slide Show view). You may see blank slides in the “Normal” or “Slide Sorter” views. All animations will appear after viewing in Presentation Mode and playing each animation. Most animations will require the latest version of the Flash Player, which is available at http://get.adobe.com/flashplayer.

22. The human genome contains about 20,325 genes - However, these encode about 100,000 mRNAs, which in turn specify more than a million proteins Several events account for the fact that proteins outnumber genes Maximizing Genetic Information

23. Maximizing Genetic Information Figure 11.8 Figure 11.11

24. The “genes in pieces” pattern of exons and introns and alternate splicing help to greatly expand the gene number Maximizing Genetic Information Figure 11.9

25. An intron in one gene’s template strand may encode a protein on the coding strand Information is also maximized when a protein undergoes post-translational modifications - Addition of sugars and lipids to create glycoproteins and lipoproteins Maximizing Genetic Information

26. Another way that one gene can encode more than one protein is if the protein is cut to yield two products This happens in dentinogenesis imperfecta - Caused by a deficiency in the two proteins DPP and DSP - Both are cut from the same DSPP protein Maximizing Genetic Information

27. Dentinogenesis Imperfecta • Caused by deficiency in proteins DPP and DSP • Both are cut from same larger protein Figure 11.10

28. DPP and DSP Figure 11.10 Figure 11.13b

29. Only 1.5% of human DNA encodes protein Rest of genome includes: - Viral DNA - Noncoding RNAs - Introns - Promoters and other control sequences - Repeated sequences Most of the Human GenomeDoes Not Encode Protein

30. About 8% of our genome is derived from RNA viruses called retroviruses - This is evidence of past infection - Sequences tend to increase over time Viral DNA Figure 11.11

31. Nearly all of the human genome can be transcribed, and much of it is in the form of noncoding RNAs (ncRNAs) This includes rRNAs and tRNAs However, there are hundreds of thousands of other ncRNAs - These are transcribed from pseudogenes - But are not translated into protein Noncoding RNAs

32. Transposons are the most abundant type of repeat - Sequences that jump about the genome - Alu repeats can copy themselves - Comprise about 2-3% of the genome Rarer classes of repeats include those that comprise telomeres, centromeres, and rRNA gene clusters Repeats

33. Transposon Animation Please note that due to differing operating systems, some animations will not appear until the presentation is viewed in Presentation Mode (Slide Show view). You may see blank slides in the “Normal” or “Slide Sorter” views. All animations will appear after viewing in Presentation Mode and playing each animation. Most animations will require the latest version of the Flash Player, which is available at http://get.adobe.com/flashplayer.

34. Table 11.4