Chromosome Structure- Chapter 11

1. Chromosome Structure- Chapter 11

2. Where we’re going • Do some math on DNA- lengths. • Tour of a few types of chromosomes • Endosymbiosis • Some time spent on Eukaryotic chromosome structure • Some repetitive DNA types • Some new information about Epigenetics

3. I. The problem: DNA is LONG: • 3.4 nm/turn of the helix, 0.34 nM (~ 1/3 nM)/ base pair. • There organism is always much smaller than the DNA- so it has to be coiled. • Virus- 20X 50 nm, 50,000 bp, or 17microns of DNA • Bacteria- 4.6 million bp, or 1500 microns of DNA • US- 6 billion bp, or 2 meters of DNA!

4. availability- • In addition, there’s the problem of availability- we can’t just pack our DNA away, since it has to be available for transcription as well.

5. II. Various genomes, their structure and packaging: • Viruses: these have a variety of DNA & types; they need to package their DNA, but it doesn’t need to be available. • Bacteria: coil it into a nucleoid with histone-like proteins (Hu & H); much looser, however • Mitochondria/chloroplasts: Endosymbiosis: they are thought to have evolved from symbiotic bacteria; coiling is similar to that of bacteria

6. How long in mm is a yeast’s genome- ~12 megabases • 1/3 nm/base * 12*10^6bases= 4X 10^6 nm • And, thanks to Kara- reminder that you can get help from Olivia today, 11-12:30! • I think she’s in Student Support Services.

7. Thus, a chloroplast or mitochondria is a mosaic of nuclear and mitochondrial proteins. Endosymbiosis- evidence: Circular DNA Prokaryotic-like ribosomes- antibiotic susceptibility! Gene order similar to that found in prokaryote The mosaic nature would NOT be expected, however.

8. Eukaryotes: • Our DNA is folded in increasing levels of compactness: • “Beads on a string”: Histones H2a, H2B, 3,&4 combine to form an octamer (2 each), which winds up 146 bp of DNA, with another 54 or so in between. The beads are nucleosomes. • 30 nM solenoid: H1 coils the nucleosomes further, into a 30 nM solenoid. This is the chromatin structure typically found in a nucleus, or folded to the next level. • These can produce chromatin loops- loops of solenoids, about 300 nm in size.

9. nucleosomes 30 nm solenoid, or chromatin fiber Chromatin fiber loops

10. Heterochromatin and euchromatin: • Packaging also alters availability for transcription • Two major types of chromatin: euchromatin and heterochromatin. • Heterochromatin is transcriptionally inert, and tends to be more condensed. Genes placed within heterochromatin are turned off- a position effect. Heterochromatin is also replicated later in S phase than euchromatin. • The euchromatin regions are less condensed, and the active genes are found in these regions, but not all euchromatin is active.

11. What goes on in our chromosomes: http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.figgrp.620 This is the protein-coding regions!

12. Two special chromosomes- polytene and lampbrush large chromosomes from salivary glands of Diptera that have hundreds of strands of DNA together, along with homologous chromosomes stuck together;

13. Lampbrush: these are chromosomes found in frog eggs, that are stuck in diplotene- and actively producing components for the eggs. They are again elongated, and active regions are shown by uncoiling from the main chromosome.

14. Repetitive DNA Obviously Functional repetitive: rRNA, (~ 400 copies/cell, centromere and telomere DNA How do we know about the copy number of these????

15. Middle repetitive, unknown/no function: VNTR’s- just saw them- important for DNA fingerprinting- repeats of 15-100 bp’s • Some of this used to be called “junk DNA”- however, there is a growing body of evidence that this DNA is functioning, but not making proteins; much of it is transcribed, and may have a role in control of gene expression.

16. Other middle repetitive DNA- LINES and SINES- these are remnants of retrotransposons- RNA that is able to make a DNA copy, like a retrovirus: • RT • RNA DNA  insert into genome transcribed into RNA • These pieces have the remnants of RT(reverse transcriptase) in them- why we think they are remnant retrotransposons. • The difference between them and a retrovirus is that retroviruses can leave the cell- make a virus particle and exit. So, you can think of retrotransposons as defective retroviruses.

18. Epigenetics- new subject • What- heritable traits that are not coded by our genes. • Methylation of DNA (lowers transcription), and Acetylation of histones (activates) becomes heritable. For example: • http://www.ncbi.nlm.nih.gov/pubmed/16391557 • http://www.ncbi.nlm.nih.gov/pubmed/11368478?dopt=Abstract&holding=npg

19. Data came from Swedish region with regular feast and famine conditions. • If the Paternal Grandfather was fed too much when he was 9-12, then the children had shorter life expectancy • Other studies show effects of starvation and smoking on obesity

20. Toxic legacy.In a controversial finding, exposing a pregnant rat to a toxin had health effects for three generations. J Kaiser Science 2014;343:361-363 Published by AAAS

21. Things to know- Ch 11 • All genomes need folding- only viral g. don’t also need to function, H & Hu • DNA length calculations- KNOW YOUR WAY AROUND THE SMALL END OF THE METRIC SYSTEM!!!!! • Endosymbiosis • Folding of Euk. Chromosome • Repetitive DNA: functional parts, how we know, LINES, SINES, life cycle of a retrotransposon

22. Quiz topics • DNA length problem • Folding- beads on a string, H2a,H2b, H3, H4, chromatin loops with H1 • Where do we find polytene and lampbrush chromosomes??? • What’s a retrotransposon?? • What are some functional repetitive DNA’s, and what do they do??