Chapter 1 Introduction to Genetics

Genetics : the study of inheritance

History of Genetics
Early civilizations Mayans with maize, Chinese with rice, Assyrians with date palms crossing individual plants of a species to make hybrids with more desirable characteristics Greeks : humors produced from an individual represented hereditary traits humors were combined to produce offspring Ongoing production of hybrids in agriculture and examination of reproduction

Recent history
Up to 1800s : preformation gametes contributed parts of individual that assemble or contained whole person (homunculus)

Recent history
1600s : began to challenge preformation William Harvey : theory of epigenesis substances in gametes produce adult structure

Recent history
Before 1860cell theory: cells come from preexisting cells 1. Hooke, van Leeuwenhoek observed cells in microscope 2. Brown discovered nuclei of cells 3. von Mohl described mitosis in nuclei 4. Darwin published The Origin of Species

Recent history
18601900 1. Mendel described inheritance in peas 2. Fleming described chromosomes and Waldeyer first used word chromosome 3. Hertwig described fusion of egg and sperm 4. Boveri, Rabl, van Breden showed chromosomes have continuity over generations 5. Weismann showed that nuclei determine inheritance, reductional state of cell division 6. Hertwig and Boveri described meiosis
used existing evidence and tested new hypotheses

Recent history
19001944: period of major advances in genetics 1. de Vries, Correns, and von Tschermak rediscovered Mendel's work 2. Sutton showed that meiotic behavior of chromosomes explained Mendel's results 3. Sturtevant showed that genes are linearly arranged on chromosomes 4. Stadler and Mller showed that X rays cause mutations 5. Fisher, Wright, and Haldane developed the mathematics to study evolution 6. Luria and Delbrck showed that bacteria have normal genetic systems could now use bacteria and viruses as models for genetic processes

Recent history
1944present 1. Avery et al. showed that DNA was genetic material 2. Watson and Crick determined structure of DNA 3. Arber, Smith, and Nathans et al. discovered and described restriction endonucleases 4. Berg created a recombinant DNA molecule 5. sequencing of genomes, including human
Emerging fields : genomics and proteomics

Classifications of Genetics
I. Classical geneticsconcerned with genes, chromosomes, mutations, and phenotypes -begun by Mendel 1. Mendel proposed that each organism has two units of a trait; appreciation of his work required an understanding of the segregation of chromosomes 2. He showed that traits behave independently

7 traits in pea plants, each with 2 discrete forms

Mendels two rules:

Law of segregation
Two alleles separate randomly from each other during gamete formation

Law of independent assortment

The alleles of different genes sort independently of each other into gametes

Classifications of Genetics
I. Classical genetics (contd)
3. People studied traits by looking for mutants 4. The results of many studies showed that genes are discrete units, arranged linearly on chromosomes 5. Beadle and Tatum showed that most genes make enzymes

Applications of classical genetics : Chromosomes Contain Genes and Are Carriers of the Genetic Material
Chromosome 2: Drosophila melanogaster Shows the relative positions of mutations

Applications of classical genetics :

Pedigree Analysis: Inheritance of an Autosomal Recessive Disease

Filled symbols = affected individuals

Open symbols = unaffected individuals

Applications of classical genetics :

Karyotype representation of all chromosomes in an individual

Classifications of Genetics
II. Molecular geneticsstructure and control of genetic material; the molecules of heredity 1. Watson and Crick : structure of DNA, the genetic material - proposed that mutations change the sequence of nucleotides in the DNA - proposed that DNA unzips to replicate

The DNA Double Helix

The Genetic Material

Double-stranded DNA
Repeating units of

Sugar (deoxyribose)
Phosphate

Nucleic acid base Helices held together by bases: adenine, guanine, cytosine, & thymine

The Two Strands of the Double Helix Unwind During Replication

Each strand serves as a template for a new double helix.

Classifications of Genetics
II. Molecular genetics (contd) 2. RNA polymerase makes RNA from DNA - RNA has the base U instead of T and ribose instead of deoxyribose - 3 nucleotides (codon) code for one amino acid 3. Ribosomes convert RNA sequences to amino acid sequences 4. Much of the control of gene activity is at the level of transcription

The Relationship between DNA and RNA during Transcription

During gene expression, the information contained in DNA is transcribed into RNA The sugar deoxyribose is replaced with ribose

Thymine is replaced with uracil

The Genetic Code

Groups of three nucleotide bases form a codon that specifies one of twenty naturally occurring amino acids.

Translation
The message in the mRNA is translated into amino acids at the ribosomes

rRNA ribosomal RNA, the site of protein synthesis

mRNA contains the information that will be translated

into the proteins amino acid sequence

The Central Dogma of Molecular Genetics

The flow of genetic information: DNA is transcribed into mRNA that is subsequently translated into protein

Classifications of Genetics
II. Molecular genetics (contd) 5. Recombinant DNA involves cutting DNA with restriction enzymes and making hybrid molecules - allows genes to be isolated and large amounts of useful proteins to be made - helps to identify cancer-causing genes - allowed the entire sequence of genomes, including the human genome, to be determined Genomics : the study of an organisms complete DNA or RNA makeup, organization and expression of genes, and relations of genes between species

Cloning a Gene
Recombinant DNA techniques:
Restriction endonucleases

-Enzymes that cut DNA

Plasmids -Small, circular extrachromosomal DNA found in some bacteria Ligase -Seals DNA fragments together

Insertion of the foreign DNA into a plasmid allows the foreign gene to grow inside a bacteria

Classifications of Genetics
III. Population and Evolutionary geneticsmechanisms that result in changes in allele frequency in populations over time. 1. Hardy and Weinberg : rules for genetic equilibrium - no change in gene frequencies occurs without selection - gives a baseline to see whether selection is occurring 2. Recent results indicate much polymorphism (variation in alleles) within populations, but this variation does not select for differences in traits 3. Punctuated equilibrium changes are not graded but may occur in bursts. 4. Sociobiology social behavior may be under the control of genes

Choice of Model Organisms in Genetics

Factors : quick generation time, many offspring, growth in small space, application to other organisms, has sequenced DNA Drosophila melanogaster (fruit fly) - short generation (two weeks), easily grown, large chromosomes, - many scoreable phenotypes Escherichia coli - short generation (20 minutes) - small number of genes - easily grown Viruses - simple structure - one hundred fold increase in one hour Scientists discover a phenomenon and then need to test its universality in other systems

Applications of Genetics to the Human Population

Treatments for diseases
Genetically manipulated food crops Genetic Counseling

A Boy with Severe Combined Immunodeficiency Disease (SCID)

Bubble-boy disease

Absence of adenine deaminase (ADA)

Gene therapy: Ashanti DeSilva -Wild-type ADA gene introduced into T cells -T cells reintroduced in the body and migrate to bone marrow -T cells produce ADA at low normal but high enough for a normal life