Chapter 16 The Molecular Basis of Inheritance

Question? Traits are inherited on chromosomes, but what in the chromosomes is the genetic material? Two possibilities: Protein DNA

Qualifications Protein: DNA: very complex. high specificity of function. DNA: simple. not much known about it (early 1900’s).

For testing: Name(s) of experimenters Outline of the experiment Result of the experiment and the importance of the result

Griffith - 1928 Pneumonia in mice. Two strains: S - pathogenic R - harmless

Griffith’s Experiment

Result Something turned the R cells into S cells. Transformation - the assimilation of external genetic material by a cell.

Problem Griffith used heat. Heat denatures proteins. So could proteins be the genetic material? DNA - heat stable. Griffith’s results contrary to accepted views.

Avery, McCarty and MacLeod - 1944 Repeated Griffith’s experiments, but added specific fractions of S cells. Result - only DNA transformed R cells into S cells. Result - not believed.

Hershey- Chase 1952 Genetic information of a virus or phage. Phage - virus that attacks bacteria and reprograms host to produce more viruses.

Bacteria with Phages

Phage Components Two main chemicals: Protein DNA Which material is transferred to the host?

Used Tracers Protein - CHONS, can trace with 35S. DNA - CHONP, can trace with 32P.

Experiment Used phages labeled with one tracer or the other and looked to see which tracer entered the bacteria cells.

Result DNA enters the host cell, but the protein did not. Therefore: DNA is the genetic material.

Picture Proof

Chargaff - 1947 Studied the chemical composition of DNA. Found that the nucleotides were in certain ratios.

Chargaff’s Rule A = T G = C Example: in humans, A = 30.9% T = 29.4%

Why? Not known until Watson and Crick worked out the structure of DNA.

Watson and Crick - 1953 Used X-ray crystallography data (from Rosalind Franklin) Used model building. Result - Double Helix Model of DNA structure. (One page paper, 1953).

Rosalind Franklin

Book & Movies “The Double Helix” by James Watson- His account of the discovery of the shape of DNA Movie – The Double Helix

DNA Composition Deoxyribose Sugar (5-C) Phosphate Nitrogen Bases: Purines Pyrimidines

DNA Backbone Polymer of sugar-phosphate. 2 backbones present.

Nitrogen Bases Bridge the backbones together. Purine + Pyrimidine = 3 rings. Constant distance between the 2 backbones. Held together by H-bonds.

Chargaff’s Rule Explained by double helix model. A = T, 3 ring distance. G = C, 3 ring distance.

Watson and Crick Published a second paper (1954) that speculated on the way DNA replicates. Proof of replication given by others.

Replication The process of making more DNA from DNA. Problem: when cells replicate, the genome must be copied exactly. How is this done?

Models for DNA Replication Conservative - one old strand, one new strand. Semiconservative - each strand is 1/2 old, 1/2 new. Dispersive - strands are mixtures of old and new.

Replication Models

Meselson - Stahl late 1950’s Grew bacteria on two isotopes of N. Started on 15N, switched to 14N. Looked at weight of DNA after one, then 2 rounds of replication.

Results Confirmed the Semiconservative Model of DNA replication.

Replication - Preview DNA splits by breaking the H-bonds between the backbones. Then DNA builds the missing backbone using the bases on the old backbone as a template.

Origins of Replication Specific sites on the DNA molecule that starts replication. Recognized by a specific DNA base sequence.

Prokaryotic Circular DNA. 1 origin site. Replication runs in both directions from the origin site.

Eukaryotic Cells Many origin sites. Replication bubbles fuse to form new DNA strands.