Orientation to Genetics & Molecular Biology

Where I'm coming from in Bio2250 - Principles of Genetics

Course Philosophy

Genetics is traditionally taught 'Peas first, DNA later'. Facts are presented and concepts are developed in the historical order in which they were discovered. After re-discovery of Mendel's work in 1900, genetics courses were taught for fifty years without any understanding of the molecular nature of the gene, and emphasized the analysis of crosses to understand the nature of heredity. After the discovery of the structure of DNA in 1953, the historical-logical approach continued to work well through the unraveling of the "Central Dogma" (DNA makes RNA makes Protein) by the early 1970s. In those days, we arrived at an understanding of protein synthesis, and the end of the course, simultaneously.

However, 2003 was the 50^th anniversary of the discovery of the structure of DNA. The first complete human DNA genome sequence was published in 2004. Bioinformatic interpretation of complete genomes is emerging as the New Wave in genetics. The traditional approach requires the pretense that, when we begin by talking about round and wrinkled peas, the student does not know about DNA, because Mendel didn't. Genetics and molecular biology have proliferated in so many directions that a single introductory course struggles to be comprehensive. Further, there is an ever-widening stretch between what foundational concepts can be taught and what is required to understand molecular genetics. Most recently, the current revolution in genomics have become technically so involved that it is difficult to present the complete logic, and we must skip to summaries of conclusions, and rely on databases for useful information.

Bio2250 reverse the traditional order: it is taught "DNA first, peas later". We begin with the molecular biology of DNA structure and protein function, build on this foundation to introduce the behaviour of genes on chromosomes and in crosses, then move onto modern & contemporary developments in molecular genetics. A course that begins, "DNA is a double-helix that is replicated semi-conservatively...." (a standing broad jump over 50 years of classical genetics) serves to remind most students of material known at least since high school. Analysis of the classical molecular experiments of Hershey & Chase, Watson & Crick, and Meselson & Stahl, and others, remain invaluable introductions to scientific inference and problem solving (and is included in Biol4241 - Advanced Genetics). They are however not critical to understanding how DNA functions. Likewise, it is necessary to understand in detail how the Genetic Code works, and less so to know how Nirenberg & Khorana figured it out in the first place. An initial grounding in the processes of molecular biology equips us to talk about current topics such as DNA cloning, Genetic Engineering, Biotechnology, and Bioinformatic results from the Human Genome Project. Most of molecular genetics is doing in a test tube what goes on in a cell. If you understand nucleic acid structure, base pairing rules, semi-conservative replication, polynucleotide directionality, and translation / translitteration of nucleic acids, you can understand molecular cloning, in vitro gene amplification, DNA sequencing in its various forms. With such a background, and an orientation to modern experimental techniques, I hope that the course will empower students to investigate further areas of individual interest.

THE DIFFERENCE IN APPROACH MAY BE SUMMARIZED AS FOLLOWS.

The traditional method of Genetics is the analysis of crosses. The traditional method of teaching genetics is to observe the phenotypes from crosses to make inferences about genotypes. For example, we teach that peas have genes "for" characters such such as "seed shape" or "colour", which exist in alternative phenotypes such as round versus wrinkled, or green vs yellow. In the same way, humans have genes "for" genetic diseases such as phenylketonuria. For each gene, we examine the ratio obtained in crosses between alternative forms, or the pattern of inheritance in family pedigrees. We then describe the two alternative alleles in any individual as dominant or recessive. With the advent of molecular biology, we acknowledge the expression of alternative alleles as due to variations in proteins, which in turn are predictable consequence of mutational changes in DNA sequences.

The modern method is to observe how DNA genotypes influence protein-based metabolic pathways that produce characteristic phenotypes, the consequences of mutations in DNA for alteration of the outcomes of these pathways, and the interactions of the alleles involved in terms of how they affect those phenotypes. For example, we will see that in Peas, there is a DNA segment that codes for a Starch Branching Protein, which when modified causes a loss of turgor pressure in seeds, and a "wrinkled" appearance. Similarly, in humans there is a gene that codes for the enzyme Phenylalanine Hydroxylase, that various alleles of this gene produce higher or lower levels of PAH, and that the biochemical interaction between the particular pair of alleles that an individual has inherited determines whether or not that individual manifests a diseasephenotype called "Phenylketonuria". We understand "dominant" and "recessive" as descriptions of a phenotype that is a consequence of a molecular genotype involving DNA and protein, rather than intrinstic properties of bead-like genes on a string. The use of molecular biology to understand the flow of information from DNA to phenotype is sometimes called "Reverse Genetics" because it reverses the traditional genetic logic, despite the fact that "DNA makes RNA makes Protein" is a forward process.

The Social Contract

1. I expect that all students will attend all lectures.
Exams are based on lecture material, not on the text.
Doing all of the assigned homework problems is the best preparation for exams.

2. As a matter of courtesy to other students and the lecturer, during lectures please:
Silence your cell phones.
      Do not make or receive phone calls.
Do not send or answer text messages.
Do not talk with your classmates.

3. When you send me e-mail, please include '2250' in the subject line, to keep it from being sent to the Trash.
     Please include a polite salutation: Dear Dr Carr, Hi Prof, Hey Steve, or something like that. It sounds better.

4. Average course marks in a recent year were:

    Midterm I       69%
    Midterm II        65%
    Final                56%
    Labs        92%
    Course       68%

   Lab marks are purposely kept high: the exercises are intended to guide you through a hands-on experience with fundamental genetic concepts, rather than to make you sweat about marks. Do not assume that a high lab mark going into the Final exam guarantees a high mark for the course. Exams are intentionally tougher. It is a serious mistake to slack off studying for the Final on such an assumption.