The Molecular Basis of Inheritance Chapter 16 The Molecular Basis of Inheritance

Overview: Life’s Operating Instructions Hereditary information is encoded in DNA and reproduced in all cells of the body This DNA program directs the development of biochemical, anatomical, physiological, and (to some extent) behavioral traits © 2011 Pearson Education, Inc.

Figure 16.1 Figure 16.1 How was the structure of DNA determined?

Sugar–phosphate backbone Figure 16.5 Sugar–phosphate backbone Nitrogenous bases 5 end Thymine (T) Adenine (A) Cytosine (C) Figure 16.5 The structure of a DNA strand. Phosphate Guanine (G) Sugar (deoxyribose) DNA nucleotide Nitrogenous base 3 end

Key features of DNA structure (b) Partial chemical structure Figure 16.7a 5 end C G Hydrogen bond C G 3 end G C G C T A 3.4 nm T A G C G C C G A T 1 nm C G T A C G G C C Figure 16.7 The double helix. G A T A T 3 end A T 0.34 nm T A 5 end (a) Key features of DNA structure (b) Partial chemical structure

(c) Space-filling model Figure 16.7b Figure 16.7 The double helix. (c) Space-filling model

Replication: Basics When? What? Key players and roles?

Replication

Meselson-Stahl experiment

Which one can we eliminate?

How does DNA’s structure effect the replication process? Enzymes can only add to the 3’ end Leading and lagging strands

Origin of replication 3 5 RNA primer 5 3 Sliding clamp 3 Figure 16.15b Origin of replication 3 5 5 RNA primer 3 Sliding clamp 3 DNA pol III Parental DNA 5 3 5 Figure 16.15 Synthesis of the leading strand during DNA replication. 5 3 3 5

Overall directions of replication Figure 16.15a Overview Leading strand Lagging strand Origin of replication Primer Leading strand Lagging strand Figure 16.15 Synthesis of the leading strand during DNA replication. Overall directions of replication

Replicating the Ends of DNA Molecules Limitations of DNA polymerase create problems for the linear DNA of eukaryotic chromosomes The usual replication machinery provides no way to complete the 5 ends, so repeated rounds of replication produce shorter DNA molecules with uneven ends This is not a problem for prokaryotes, most of which have circular chromosomes © 2011 Pearson Education, Inc.

Ends of parental DNA strands Leading strand Lagging strand 3 Figure 16.20 5 Ends of parental DNA strands Leading strand Lagging strand 3 Last fragment Next-to-last fragment Lagging strand RNA primer 5 3 Parental strand Removal of primers and replacement with DNA where a 3 end is available 5 3 Second round of replication Figure 16.20 Shortening of the ends of linear DNA molecules. 5 New leading strand 3 New lagging strand 5 3 Further rounds of replication Shorter and shorter daughter molecules

Ends of parental DNA strands Lagging strand 3 Figure 16.20a 5 Leading strand Ends of parental DNA strands Lagging strand 3 Last fragment Next-to-last fragment RNA primer Lagging strand 5 3 Parental strand Figure 16.20 Shortening of the ends of linear DNA molecules. Removal of primers and replacement with DNA where a 3 end is available 5 3

Second round of replication Figure 16.20b 5 3 Second round of replication 5 New leading strand 3 New lagging strand 5 3 Figure 16.20 Shortening of the ends of linear DNA molecules. Further rounds of replication Shorter and shorter daughter molecules

Eukaryotic chromosomal DNA molecules have special nucleotide sequences at their ends called telomeres Telomeres do not prevent the shortening of DNA molecules, but they do postpone the erosion of genes near the ends of DNA molecules It has been proposed that the shortening of telomeres is connected to aging © 2011 Pearson Education, Inc.

Figure 16.21 Figure 16.21 Telomeres. 1 m

If chromosomes of germ cells became shorter in every cell cycle, essential genes would eventually be missing from the gametes they produce An enzyme called telomerase catalyzes the lengthening of telomeres in germ cells © 2011 Pearson Education, Inc.

The shortening of telomeres might protect cells from cancerous growth by limiting the number of cell divisions There is evidence of telomerase activity in cancer cells, which may allow cancer cells to persist © 2011 Pearson Education, Inc.

Concept 16.3 A chromosome consists of a DNA molecule packed together with proteins The bacterial chromosome is a double-stranded, circular DNA molecule associated with a small amount of protein Eukaryotic chromosomes have linear DNA molecules associated with a large amount of protein In a bacterium, the DNA is “supercoiled” and found in a region of the cell called the nucleoid © 2011 Pearson Education, Inc.

Chromatin, a complex of DNA and protein, is found in the nucleus of eukaryotic cells Chromosomes fit into the nucleus through an elaborate, multilevel system of packing For the Cell Biology Video Cartoon and Stick Model of a Nucleosomal Particle, go to Animation and Video Files. Animation: DNA Packing © 2011 Pearson Education, Inc.

Nucleosome (10 nm in diameter) Figure 16.22a Nucleosome (10 nm in diameter) DNA double helix (2 nm in diameter) H1 Histone tail Figure 16.22 Exploring: Chromatin Packing in a Eukaryotic Chromosome Histones Nucleosomes, or “beads on a string” (10-nm fiber) DNA, the double helix Histones

Replicated chromosome (1,400 nm) Figure 16.22b Chromatid (700 nm) 30-nm fiber Loops Scaffold 300-nm fiber 30-nm fiber Figure 16.22 Exploring: Chromatin Packing in a Eukaryotic Chromosome Replicated chromosome (1,400 nm) Looped domains (300-nm fiber) Metaphase chromosome

DNA double helix (2 nm in diameter) Figure 16.22c DNA double helix (2 nm in diameter) Figure 16.22 Exploring: Chromatin Packing in a Eukaryotic Chromosome

Nucleosome (10 nm in diameter) Figure 16.22d Nucleosome (10 nm in diameter) Figure 16.22 Exploring: Chromatin Packing in a Eukaryotic Chromosome

Chromatin undergoes changes in packing during the cell cycle At interphase, some chromatin is organized into a 10-nm fiber, but much is compacted into a 30-nm fiber, through folding and looping Though interphase chromosomes are not highly condensed, they still occupy specific restricted regions in the nucleus © 2011 Pearson Education, Inc.

Figure 16.23 Figure 16.23 Impact: Painting Chromosomes 5 m

Loosely packed chromatin is called euchromatin Most chromatin is loosely packed in the nucleus during interphase and condenses prior to mitosis Loosely packed chromatin is called euchromatin During interphase a few regions of chromatin (centromeres and telomeres) are highly condensed into heterochromatin Dense packing of the heterochromatin makes it difficult for the cell to express genetic information coded in these regions © 2011 Pearson Education, Inc.

Histones can undergo chemical modifications that result in changes in chromatin organization © 2011 Pearson Education, Inc.

Evolution of the Genetic Code The genetic code is nearly universal, shared by the simplest bacteria to the most complex animals Genes can be transcribed and translated after being transplanted from one species to another © 2011 Pearson Education, Inc. 36

(a) Tobacco plant expressing (b) Pig expressing a jellyfish Figure 17.6 Figure 17.6 Expression of genes from different species. (a) Tobacco plant expressing (b) Pig expressing a jellyfish a firefly gene gene