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 and concepts are developed in the same order in which they were discovered historically. Genetics courses were taught for fifty years without any clear understanding of the molecular nature of the gene. The ontogeny of most courses follows this phylogeny. However, a certain pretense is required: when we talk about round and wrinkled peas, we pretend you don't know about DNA, because Mendel didn't. This approach works well through the unraveling of the "Central Dogma" (DNA makes RNA makes Protein) in 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, and the molecular revolution in biology continues to accelerate. Genetics and molecular biology have proliferated in so many directions that a single introductory course struggles to be comprehensive. Worse, there is an ever-widening gap between what can be taught and what is required to understand molecular genetics in 'general science' journals like "Science" or "Nature". Recent experiments in genomics have become technically so involved that it is difficult to present the complete logic, and we must skip to summaries of conclusions. How can the connection be made?

Bio2250 is taught "DNA first, peas later". I reverse the traditional order. We begin with an introduction to the molecular biology of DNA structure and protein function, and build on this foundation to introduce the behaviour of genes on chromosomes and in crosses. 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 in a general way at least since high school. The logic of the classical experiments of Hershey & Chase, Watson & Crick, and Meselson & Stahl, and others, is a valuable introduction to scientific inference and problem solving. It is not crucial 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 the Human Genome Project. Selected experiments are still analyzed in detail, to emphasize the problem-solving approach in genetics. 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, polynucleotide directionality, and replication, you can understand vector insertion and molecular cloning. 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 teaching genetics is to understand phenotype in terms of genotype, and show the genotypic basis of phenotypes. The method of analyzing crosses is the traditional basis of "Genetics". That is, we teach that Peas have genes "for" alternative characteristics such as round vs wrinkled, or green vs yellow. In the same way, Humans have a gene "for" a genetic disease such as phenylketonuria. For each gene, we talk about in terms of one phenotype "dominating" another, and two alternative alleles being dominant or recessive. The nature of these alleles turns out to be due to variations the protein sequence, which is in turn a predictable consequence of particular changes in DNA sequences.

The modern method is to show how DNA genotypes influence protein 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 disease 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 protein to phenotype is sometimes called "Reverse Genetics" .

The Social Contract

1. I expect that all students will attend all lectures.
Exams are based on lecture material, not on the text.

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 Carr, 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.

Other courses in Genetics at Memorial:

Population genetics is covered in Bio 2900 (Principles of Evolution & Systematics), another course in the core curriculum. My own research is an application of molecular genetics to evolutionary biology. You'll hear more about this later.

Molecular Biology of Nucleic Acids is covered in Biochemistry 3107 (Dr. Mulligan), which goes into greater depth on some of these same topics, from the perspective of a biochemist. Courses in Prokaryotic and Eukaryotic Gene Regulation are also taught through Biochemistry.

Advanced Genetics (Bio4241) is typically offered in alternate years. This course considers classic and current genetics experiments in detail, and cover additional topics (eg, Immunogenetics, Cancer Genetics, Quantitative Genetics, Developmental Genetics) in greater detail.

Fundamentals of Genetic Biotechnology (Bio4900) is a hands-on lab course offerred as a three-week intensive introduction to DNA extraction, PCR, Cloning, DNA sequencing, and bioinformatic interpretation of DNA sequence data.

New courses in Genomics, Plant Genetics, Developmental Genetics, etc., are being developed by new faculty, as part of a concentration in Genomics & Cell Biology.