CHAPTER 1Genetics: An IntroductionPeter J. Russelledited by Yue-Wen Wang Ph. D. Dept. of Agronomy, NTUA molecular Approach 2nd Edition

Classical and Modern Genetics1.Humans have long understood that offspring tend to resemble parents, and have selectively bred animals and plants for many centuries. The principles of heredity were first explained by Mendel in the mid nineteenth century, using defined crosses of pea plants.

Classical and Modern Genetics2.In the last century, genetics has become an important biological tool, using mutants to gain an understanding of specific processes. This work has included:a. Analyzing heredity in populations.b. Analyzing evolutionary processes.c. Identifying genes that control steps in processes.d. Mapping genes.e. Determining products of genes.f.Analyzing molecular features of genes and regulation of gene expression.

Classical and Modern Genetics3.Recent important milestones in genetics include:a. Bergs construction (1972) of the first recombinant DNA molecule in vitro.b. Boyer and Cohens first cloning (1973) of a recombinant DNA molecule.c. Invention by Mullis (1986) of the polymerase chain reaction (PCR) to amplify specific DNA sequences

Classical and Modern Genetics4.Completion of genomic sequencing for an increasing number of organisms has spawned the new field of genomics. Knowledge of individual genes and their regulation will be important to basic biological research, as well as to specific applications such as medical genetics.5.Powerful new techniques in genetics raise important ethical, legal and social issues that will need thoughtful solutions.

Basic Concepts of GeneticsThe concepts and processes of genetics summarized here are intended as a review from the introductory biology course.

DNA, Genes and Chromosomes1.Genetic material of both eukaryotes and prokaryotes is DNA (deoxyribonucleic acid). Many viruses also have DNA, but some have RNA genomes instead.2.DNA has two chains, each made of nucleotides composed of a deoxyribose sugar, a phosphate group and a base. The chains form a double helix (Figure 1.1).

Fig. 1.1 DNAPeter J. Russell, iGenetics: Copyright Pearson Education, Inc., publishing as Benjamin Cummings.

DNA, Genes and Chromosomes3.There are four bases in DNA: A (adenine), G (guanine), C (cytosine) and T (thymine).a. In RNA, U (uracil) replaces T.b. The sequence of bases determines the genetic information.c. Genes are specific sequences of nucleotides that pass traits from parents to offspring.

DNA, Genes and Chromosomes4.Genetic material in cells is organized into chromosomes (literally colored body because it stains with biological dyes).a. Prokaryotes generally have one circular chromosome.b. Eukaryotes generally have:i. Linear chromosomes in their nuclei, with different species having different numbers of chromosomes.ii. DNA in organelles (e.g., mitochondria and chloroplasts) that is usually a circular molecule.

Transmission of Genetic Information1.Transmission of traits from parents to offspring was addressed in Mendels work with peas.a. He selected strains that differed in particular traits (e.g., smooth or wrinkled seeds, purple or white flowers) (Figure 1.2).b. After making genetic crosses, he counted the appearance of traits in the progeny and analyzed the results mathematically.c. He concluded that each organism contains two copies of each gene, one from each parent, and that alternative versions of the genes (alleles) exist (e.g., pea seed color alleles are yellow, Y, and green, y).

Transmission of Genetic Information2.An organism that has the same alleles for a trait is homozygous (e.g., YY or yy). An organism with two different alleles (e.g., Yy) is heterozygous.3.The complete genetic makeup of an organism is its genotype. All observable traits of an organism are its phenotype. The genotype interacts with both internal and external environments of the organism to produce the phenotype.

Transmission of Genetic Information4.Mendel considered the factors controlling the phenotypes he observed in peas.a. He deduced that the factors (now called genes) segregate randomly into gametes (Mendels first law, the Principle of Segregation).b. The two factors for a particular trait assort independently of factors controlling other traits (Mendels second law, the Principle of Independent Assortment).c. An example is seed color in peas:i. True-breeding plants with yellow seeds (YY) are crossed with true-breeding plants with green seeds (yy).ii. The progeny (F1) have yellow seeds, and a heterozygous genotype (Yy).iii. When the progeny self-pollinate, the F2 contains threeyellow:1 green, with genotypic ratios of 1 YY : 2 Yy : 1 yy.

Transmission of Genetic Information5.Mendel died in 1884, the material basis of gene segregation was shown until 1902.6.In 1902, Sutton and Boveri proposed that genes are on chromosomes and their movement explainable by the segregation of chromosomes during meiosis.

Expression of Genetic Information1.Gene expression is the process by which a gene produces its product and the product carries out its function.2.Beadle and Tatum (1941) showed in the fungus Neurospora crassa that there is a relationship between a gene and each enzyme needed in a biochemical pathway, resulting in the one gene-one enzyme hypothesis (now modified to one gene-one polypeptide, since not all proteins are enzymes and some require more than one polypeptide).

Expression of Genetic Information3.Production of proteins requires two steps:a. Transcription involves an enzyme (RNA polymerase) making an RNA copy of part of one DNA strand. There are four main classes of RNA:i. Messenger RNAs (mRNA), which specify the amino acid sequence of a protein by using codons of the genetic code.ii. Transfer RNAs (tRNA).iii. Ribosomal RNAs (rRNA).iv. Small nuclear RNAs (snRNA), found only in eukaryotes.b. Translation converts the information in mRNA into the amino acid sequence of a protein using ribosomes, large complexes of rRNAs and proteins.

Fig. 1.3 TranscriptionPeter J. Russell, iGenetics: Copyright Pearson Education, Inc., publishing as Benjamin Cummings.

Expression of Genetic Information

Expression of Genetic Information4.Only some of the genes in a cell are active at any given time, and activity also varies by tissue type and developmental stage. Regulation of gene expression is not completely understood, but it has been shown to involve an array of controlling signals.a. Jacob and Monod (1961) proposed the operon model to explain prokaryotic gene regulation, showing that a genetic switch is used to control production of the enzymes needed to metabolize lactose. Similar systems control many genes in bacteria and their viruses.b. Genetic switches used in eukaryotes are different and more complex, with much remaining to be learned about their function.

Sources of Genetic VariationGenetic differences between organisms arise from mutations, recombination and selection. All three are necessary for the process of evolution.a. Mutations (heritable changes in the genetic material) may be spontaneous or induced. Only those that escape the cells DNA repair mechanisms are fixed in the genome and passed to the next generation.b. Recombination (exchange of genetic material) is produced by enzymes that cut and rejoin DNA molecules.i. In eukaryotes, recombination via crossing-over is common in meiosis and occurs more rarely in mitosis.ii. In prokaryotes, recombination may occur when two DNA molecules with similar sequences become aligned.c. Selection (favoring particular combinations of genes in a given environment) was described by Darwin. Its main consequence is to change the frequency of genes affecting traits under selection. Different genotypes contribute alleles to the next generation in proportion to their selective advantage.

Geneticists and Genetics Research1.Enormous amounts of genetic research have been done, typically using the hypothetico-deductive method of investigation, which consists of:a. Making observations.b. Forming hypotheses to explain the observations.c. Making experimental predictions based on the hypotheses.d. Testing the predictions, resulting in new observations and another cycle of research.

Geneticists and Genetics Research2.Research is unpredictable, which helps motivate scientists by making the work exciting. (An example of unpredictability is McClintocks work with corn kernel color, which led to the discovery of transposons).

The Sub-disciplines of Genetics1.Genetics is often divided into four subdisciplines:a. Transmission (classical) genetics deals with movement of genes and genetic traits from parents to offspring, and with genetic recombination.b. Molecular genetics deals with the molecular structure and function of genes.c. Population genetics studies heredity in groups for traits determined by one or a few genes.d. Quantitative genetics studies group hereditary for traits determined by many genes simultaneously.

The Sub-disciplines of Genetics2. Historically, transmission genetics developed first, followed by population, quantitative and finally molecular genetics.3. Genes influence all aspects of an organisms life, and are relevant to all fields of biology.

Basic and Applied Research1. Basic research is done to understand fundamental phenomena, regardless of usefulness for immediate applications. Most of the information in this book comes from basic research. The results of basic research are used to fuel basic and applied research.2. Applied research has the goal of an immediate application, and is important in agriculture and medicine, producing improved livestock and crop plants, as well as diagnostic tests and treatments for diseases.

Basic and Applied Research3. Basic and applied research are closely related, using similar techniques. Both rely on the accumulated body of information. Recombinant DNA technology is an example of basic research that has led to many applications, including:a. Plant breeding to improve disease resistance, shelf life and flavor.b. Animal breeding to develop livestock that produce leaner meat, and more milk or eggs.c. Medicines including antibiotics, hormones, clotting factors and human insulin.d. Diagnostic tests for many human diseases.e. Forensics techniques that are used in paternity testing, criminal cases and anthropological studies.

Genetic Databases and Maps1.Genetic databases have become more sophisticated as computer analysis tools have been developed. The National Center for Biotechnology Information (NCBI) is an important website for genetics (http://www.ncbi.nlm.nih.gov), which includes the following search tools:a. BLAST, a tool to compare nucleotide or protein sequences.b. GenBank, an annotated DNA sequence database.c. PubMed, which searches literature citations and abstracts and links to electronic versions of journals.d. Online Mendelian Inheritance in Man (OMIM), a database of human genes and genetic disorders.e. Entrez is a system for searching linked databases.

Genetic Databases and Maps2.Genetic maps have been constructed since 1902. They show the sites of genes (loci) on chromosomes, and genetic distances between them calculated from recombination in experimental crosses. Genetic maps can show whether genes with related functions are on the same chromosome, and are useful in cloning and genome sequencing.

Fig. 1.6Example of a genetic map, here some of the genes on chromosome 2 of the fruit fly, Drosophila melanogasterPeter J. Russell, iGenetics: Copyright Pearson Education, Inc., publishing as Benjamin Cummings.

Model Organisms1.Many organisms are used in genetic research. Desirable qualities for an experimental organism include:a. A well-known genetic history.b. A short life cycle so generations can be studied in a relatively short time.c. A large number of offspring from each mating.d. Ease of growing and handling the organism.e. Marked genetic variation within the population.

2.Eukaryotes keep their DNA in the nucleus, a discrete structure bounded by a nuclear envelope (absent in prokaryotes).3.Eukaryotes can be unicellular or multicellular.4.These eukaryotes are used in much of current genetic research:a. Saccharomyces cerevisiae (a unicellular baking yeast).b. Drosophila melanogaster (fruit fly).c. Caenorhabditis elegans (a nematode worm).d. Arabidopsis thaliana (a small weed in the mustard family).e. Mus musculus (mouse).f. Homo sapiens (human).

5.Additional eukaryotes that have made important contributions in genetics include:g. Neurospora crassa (orange bread mold).h. Tetrahymena (unicellular protozoa).i. Paramecium (unicellular protozoa).j. Chlamydomonas reinhardtii (unicellular green alga).k. Pisum sativum (garden pea).l. Zea mays (corn).m. Gallus (chicken).Figure 1.7

Fig. 1.8 Eukaryotic cellsPeter J. Russell, iGenetics: Copyright Pearson Education, Inc., publishing as Benjamin Cummings.

6.Generalized features of higher plant and animal cells are (Figure 1.8):a. A plasma membrane encloses the cytoplasm in both.b. Plant cells have a rigid cell wall.c. In both, the nucleus contains DNA complexed with proteins and organized into chromosomes.d. The nuclear envelope is two layers of semipermeable membrane with pores that allow movement of materials (e.g., ribosomes) between nucleoplasm and cytoplasm.

e. The cytoplasm contains many materials and organelles. Important in genetics are:i. Centrioles (basal bodies) are in cytoplasm of nearly all animals, but not in most plants. In animals, a pair of centrioles is associated with the centrosome region of the cytoplasm where spindle fibers are organized in mitosis or meiosis.ii. The endoplasmic reticulum (ER) is a double membrane system that runs through the cell. ER with ribosomes attached collects proteins that will be secreted from the cell or localized to an organelle.iii. Ribosomes synthesize proteins, either free in the cytoplasm or attached to the cytoplasmic side of the ER.iv. Mitochondria are large organelles surrounded by double membrane that play a key role in energy processing for the cell. They contain their own DNA encoding some mitochondrial proteins, rRNAs and tRNAs.v. Chloroplasts are photosynthetic structures that occur in plants. The organelle has a triple membrane layer, and includes a genome encoding some of the genes needed for organelle functions.

7. Prokaryotes have no nuclear envelope. All bacteria are prokaryotes, and most are single-celled, with their shape maintained by a rigid cell wall outside the cell membrane (Figure 1.9).a. Bacteria are divided into two distantly related groups:i. Eubacteria, common organisms found in other organisms and in the environment, and the type most often studied. E. coli is in this group.ii. Archaebacteria, normally found in extreme environments (e.g., hot springs, salt or methane marshes, deep ocean).b. Bacteria generally range in size from 100 nm to 10X60 mm. One species, Epulopiscium fishelsoni, is 60X800 mm, a million times larger than E. coli.

Fig. 1.9 Cutaway diagram of a generalized prokaryotic cellPeter J. Russell, iGenetics: Copyright Pearson Education, Inc., publishing as Benjamin Cummings.