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Genetics: From Genes to Genomes

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1 Genetics: From Genes to Genomes
PowerPoint to accompany Genetics: From Genes to Genomes Fourth Edition Leland H. Hartwell, Leroy Hood, Michael L. Goldberg, Ann E. Reynolds, and Lee M. Silver Prepared by Mary A. Bedell University of Georgia Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display 1 1

2 1 Genetics: The study of biological information
Introduction to Genetics in the Twenty-First Century CHAPTER CHAPTER Genetics: The study of biological information CHAPTER OUTLINE 1.1 DNA: The Fundamental Information Molecule of Life 1.2 Proteins: The Functional Molecules of Life Processes 1.3 Complex Systems and Molecular Interactions 1.4 Molecular Similarities of all Life-Forms 1.5 The Modular Construction of Genomes 1.6 Modern Genetic Techniques 1.7 Human Genetics Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1

3 Three levels of biological information
DNA Macromolecule made of nucleic acids Repository of the genetic code Proteins Macromolecules made of amino acids Amino acid sequence determined by DNA sequence Biological systems Network of interactions between molecules or groups of cells Accomplish coordinated functions Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1

4 The biological information in DNA generates an enormous diversity of living organisms
Fig. 1.1 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1

5 Complementary base pairs are a key feature of the DNA molecule
DNA is comprised of four nitrogenous bases [guanine (G), adenine (A), cytosine (C), and thymine (T)], a deoxyribose, and a phosphate G – C and A – T hydrogen bonds between each strand of the double helix The two strands of the double helix are in opposite orientation Fig. 1.2 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1

6 The information in DNA is one-dimensional and is digital
Biological information is encoded in the nucleotide sequence of DNA and each unit of information is discrete DNA sequence can be handled by computers Automated DNA sequencers can sequence about 106 base pairs/day New technologies can sequence even more DNA per day Fig. 1.3 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1

7 Organization of genetic information in cells
Genes are sequences of DNA that encode proteins Chromosomes are organelles that package and manage the storage, duplication, expression, and evolution of DNA Genomes are the entire collection of chromosomes in each cell of an organism The human genome: 24 kinds of chromosomes 3 x 109 base pairs Encodes 20,000 – 30,000 genes Figure 1.4 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1

8 Proteins are polymers of hundreds to thousands of amino acids
There are 20 different amino acids Information in DNA of a gene dictates the sequence of amino acids for the protein The order of amino acids determines the type of protein and its three dimensional structure Diversity of three-dimensional structure of protein generates an extraordinary diversity of protein function Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1

9 The amino acid sequence determines the three-dimensional shape of the protein
Chemical formulas for two amino acids Three-dimensional shapes of two proteins Figure 1.5a Figure 1.5c Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1

10 Conversion of biological information from a one- to a four-dimensional state
Fig. 1.6 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1

11 Evolution of biological information on earth
RNA may have been the first information-processing molecule Has ability to store, replicate, mutate, express information, and fold in 3-dimensions RNA is unstable so other stable macromolecules evolved DNA took over the linear information and replication functions Proteins took over the 3-dimensional folding functions All organisms alive now descended from the first organisms that adopted this molecular specialization Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1

12 RNA evolved into an intermediary in conversion of DNA information into protein
RNA is comprised of four nitrogenous bases [guanine (G), adenine (A), cytosine (C), and uracil (U)], a ribose, and a phosphate Bases are read as triplets to encode amino acid subunits of protein Fig 1.7a Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1

13 All living organisms use essentially the same genetic code
Specific triplets of RNA bases encode the 20 amino acids Figure 1.7b Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1

14 Many genes have similar functions in different organisms
Comparison of gene products in different organisms can reveal identical and similar amino acid sequences e.g. cytochrome C protein from six species Figure 1.8 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1

15 A gene from one organism can functionally replace a gene in another organism
Example: Pax6 gene is required for eye development in insects, mice, and humans Expression of human Pax6 gene in Drosophila can induce eye development Figure 1.9 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1

16 Fossil evidence for some of the major stages in the evolution of life
Duplication and divergence of genetic information is evident in the evolutionary history of life Table 1.1 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1

17 The modular construction of genomes
Hierarchical organization of information in chromosomes In eukaryotes, exons are arranged into genes Exons from different genes can be rearranged to create new combinations Genes can duplicate and diverge to create multi-gene families Multi-gene families can rapidly expand to create super- families Regulatory networks that control gene expression can change rapidly Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1

18 Evolution of gene families by duplication of ancestral genes
Gene duplication followed by sequence divergence underlies the evolution of new genes with new functions Figure 1.10 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1

19 Example of the effects of changes to a key regulatory network
Two-winged flies evolved from four-winged flies This evolutionary change was also accomplished in the lab Mutation of a regulatory network converts a normal two-winged fly into a four- winged fly Figure 1.11 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1

20 Modern genetic techniques
Genetic dissection of model organisms Inactivate a gene and observe the consequences Genome sequencing Human Genome Project Model organisms and other organisms Understanding higher-order processes that arise from interacting biological networks Genomics can rapidly analyze thousands of genes High-throughput DNA sequencing and genotyping Large-scale DNA arrays (chips) Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1

21 Genomes of five model organisms were sequenced as part of the Human Genome Project
Figure 1.12 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1

22 New global tools of genomics can analyze thousands of genes rapidly
Schematic drawing of the components of a DNA chip Figure 1.13a Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1

23 Hybridization of cDNAs made from cellular mRNAs to a DNA chip
Figure 1.13b Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1

24 Computerized analysis of chip hybridizations can be used to compare mRNA expression in two types of cells Thousands of genes can be simultaneously analyzed In this example, genes whose expression was altered by treatment with an experimental cancer drug were identified using a DNA chip Figure 1.13c Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1

25 The focus of this book is on human genetics
Genetics has powerful tools for understanding human biology Paradigm shift from studying one gene or protein at a time to studying interacting networks of many genes and proteins Molecular studies can lead to predictive and preventive medicine DNA diagnostics can be used to generate a genetic profile of an individual Design of therapeutic drugs to prevent or minimize symptoms of gene-based diseases Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1

26 Important implications of genetics to social issues
Entire genetic profiles of individuals will become available This genetic information can be used to help people Make predictions about future possibilities and risks Or, genetic information could also be used to to restrict people's lives Genetic Information Nondiscrimination Act was passed by the federal government in 2008 Prohibits discrimination on the basis of genetic tests by insurance companies and employers Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1

27 Important implications of genetics to social issues (continued)
Proper interpretation of genetic information and understanding of statistical concepts is essential Regulation and control of new technology Transgenic technology (genetic engineering) is routine in many animals Should genetic engineering of human embryos be allowed? Guidelines must be established to prevent misuse of new knowledge in human genetics Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 1

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