ASBMB Core Concepts in Biochemistry and Molecular Biology: Biological Information

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Better BiochemistryThe American Society for Biochemistry and Molecular Biology (ASBMB) has decided that the best way to teach undergraduate biochemistry is to concentrate on fundamental principles rather than facts and details. This is an admirable goal—one that I strongly support.

Over the past few months, I've been discussing the core concepts proposed by Tansey et al. (2013) [see Fundamental Concepts in Biochemistry and Molecular Biology]. The five concepts are:

1. evolution [ASBMB Core Concepts in Biochemistry and Molecular Biology: Evolution ]
2. matter and energy transformation [ASBMB Core Concepts in Biochemistry and Molecular Biology: Matter and Energy Transformation]
3. homeostasis [ASBMB Core Concepts in Biochemistry and Molecular Biology: Homeostasis]
4. biological information [ASBMB Core Concepts in Biochemistry and Molecular Biology: Biological Information]
5. macromolecular structure and function [ASBMB Core Concepts in Biochemistry and Molecular Biology: Molecular Structure and Function]

So far, I've highlighted several problems with the core concepts of evolution, matter & energy, and homeostasis. It seems as though it is easy to identify broad categories but quite difficult to agree on the core concepts within each category. It some cases, I think the "core concepts" described by Tansey et al. (2013) are incorrect or, at best, misleading.

Let's look at "Biological Information." We can all agree that information and information flow is a very important topic and there should be many important concepts within that topic. Tansey at al. (2014) start off with "The Genome."

The Genome

Two key conditions for life include the presence of powerful biological catalysts, and heritable information to guide the production of those catalysts. The information for an organism's enzymatic catalysts, as well as for proteins and RNA molecules with structural, transport, signaling, and ligand-binding functions, is stored in its genome. The genome is comprised of linear polymers of four nucleotides, called nucleic acids, assembled into unique sequences that encode the information needed to specify the macromolecules particular to that organism. An organism's genome is usually encoded in double-stranded deoxyribonucleic acid (dsDNA) polymers but the genomes of some microbes are comprised of single-stranded or double-stranded ribonucleic acid (ssRNA or dsRNA) polymers. The dsDNA polymers may be very long and encompass millions of nucleotides in each strand. Complete polymers are called chromosomes. The nucleotides of one strand of a DNA chromosome form complementary base pairs with the nucleotides of the other strand, with adenosine residues paired with thymidine, and guanosine paired with cytidine.

Hereditary information passed on from one generation of a species to the next may include all of the genome of the organism (asexual reproduction) or a portion of the genome (sexual reproduction). The heredity of multicellular organisms also depends on the transmission of mitochondrial or chloroplast dsDNA from parent to offspring. The transmission of epigenetic imprinting from one individual to the next is also important.

Students should be able to define what a genome consists of, and how the information in the various genes and other sequence classes within each genome are used to store and express genetic information.

I believe that all introductory biochemistry & molecular biology courses should spend a considerable amount of time on the structure of nucleic acids. I would have added a number of other core concepts to the description. Of course students should know about complimentary base pairs but they should also know the structure of DNA and, especially, what holds the double stranded helix together. The fact that the strands run in opposite direction is essential for understanding DNA replication, repair, and recombination.

This is one of the few times where I support teaching a specific structure in some detail. The idea here is to prove that "information" is contained in well-understood chemical structures. (Cells obey the laws of physics and chemistry.) Students should know that there's nothing magical about biological information.

This is also one of the few times where I support teaching history. The history of the discovery of DNA as the carrier of heritable information is one of the best examples of how science works. Some history is important in teaching science as a way of knowing. Most educators agree that we should be teaching students about the nature of science.

I agree with teaching the concept that the genome contains heritable information but I would make sure to cover specific information other than genes for RNAs and proteins. Students should know about information for regulating gene expression and for things like origins of replication, telomeres, etc.

I would avoid using the word "encode" unless you are referring specifically to reading frames. I would explain that a genome is defined as one complete copy of the collection of large DNA molecules in a cell. It refers to the haploid DNA content. It is not technically correct to say that sexually reproducing species pass on only a "portion of the genome."

If teachers are going to talk about transmission of heritable information outside of the normal chromosomes, I would make sure to include plasmids along with mitochondria and chloroplasts. Otherwise, it look like a course that only covers eukaryotes. (I'm not sure this is a core concept.)

If students are really going to "be able to define what a genome consists of" then one can't avoid talking about the C-value paradox and junk DNA [Five Things You Should Know if You Want to Participate in the Junk DNA Debate]. I think the structure and size of genomes are important core concepts because they help focus student's attention on biological information and what part of the genome is essential.

"Epigenetic imprinting" is a fad. It is not an important core concept. It can be covered in upper-level courses [What is epigenetics?].

Information in the Gene: Nucleotide Sequence to Biological Function

The unit of genetic information in a nucleic acid that specifies some macromolecular product (protein or RNA) is called the gene. The information in a gene is converted into single-stranded RNA in a process called transcription. Those RNAs derived from protein-encoding genes (called "messenger RNA" or mRNA), are then "translated" by ribosomes into protein molecules. Proteins consist of linear sequences of amino acid residues whose order is determined by the sequence of mRNA nucleotides, utilizing a universal genetic code (minor exceptions to code universality are readily explained by evolutionary theory).

All known organisms–bacteria, archaean, or eukaryote–utilize the same pool of 20 "standard" amino acids for protein synthesis, the same genetic code to translate mRNAs and guide that synthesis, and the same set of four nucleotides to constitute genomic nucleic acids.

Students should be able to explain the central dogma of biology (the message in DNA is transcribed into RNA and translated into protein) and relate the commonality of the process to all of life.

This would be an excellent time to teach a very fundamental concept: "what is a gene?" [What Is a Gene? ] This is a fabulous topic for a student-centered learning approach. You can have students come up with their own definitions and then try and reach a consensus. There is no universal definition that works in all cases but by the time students arrive at that conclusion they will have learned a lot.

Students need to understand the basics of information flow from DNA to RNA and protein (Sequence Hypothesis). They should understand the difference between this information flow and the real meaning of the Central Dogma of Molecular Biology [Basic Concepts: The Central Dogma of Molecular Biology]. I hope there will be a time in the future when we don't need to teach this but, for now, we need to teach it because students will have misconceptions about the meaning of the Central Dogma. Tansey et al. share those misconceptions.

I don't know how much of the mechanisms of transcription and translation are basic concepts and how much is detail. I have a tendency to over-emphasize concepts in this part of the course.

The genetic code is important. You can't say that it's "universal" because that's not exactly true. Once you qualify that statement you are obliged to mention that there are exceptions. However, it wrong to say, as Tansey et al. (2013) do, that "minor exceptions to code universality are readily explained by evolutionary theory." I don't know what part of evolutionary theory they are referring to but I can't think of any easy explanation for the genetic code variants found in some species.

Furthermore, if you are going to mention the minor exceptions (variants) then surely you have to mention the codons for the three non-standard amino acids. Don't you?

Two important topics have been neglected. First, we need to teach the important concept that there are multiple types of functional RNAs. In addition to ribosomal RNA, tRNA, and mRNA, there are many smaller RNAs that are catalysts and regulatory molecules.

Second, I think we have to cover RNA processing and modification. The core concepts are that RNA can be post-transcriptionally processed by adding or removing nucleotides and by modifying existing nucleotides. (This includes splicing and the organization of many eukaryotic genes.)

Genome Transmission from One Generation to the Next

Passing a copy of the genome to a new cellular generation requires genome duplication, a process called replication. Each strand of the double-stranded DNA comprising a chromosome is used to direct the synthesis of a complementary strand, leading to the generation of two identical dsDNA products. One copy of the replicated genome is passed to the daughter cell when the cell divides.

Students should be able to illustrate how DNA is replicated and genes are transmitted from one generation to the next in multiple types of organisms including bacteria, eukaryotes, viruses, and retroviruses.

This sounds okay to me.

The important concepts are that DNA replication is semi-conservative, the two strands are never separated, synthesis of new DNA on both strands is coordinated by assembling a molecular machine at the replication fork, synthesis occurs in one direction only, the energy for synthesis is derived from the incoming nucleotide triphosphates, DNA replication begins at specific sites in the genome called origins, and the termination of synthesis at the ends of linear chromosomes presents a problem.

Genome Maintenance

Because genetic mutations can be quite deleterious to an organism and/or its progeny, there is a low biological tolerance for genomic alterations. For this reason, the nucleic acids in chromosomes are nearly unique in that they are the objects of elaborate and energy-intensive repair processes. Repair affords a high degree of genomic stability in most organisms, and limits the rate of evolutionary processes. In higher eukaryotes, including mammals, defects in DNA repair processes produce genomic instability and can lead to cancer.

Students should be able to state how the cell insures high fidelity DNA replication and identify instances where the cell employs mechanisms for damage repair.

The important concept here is that DNA replication is error-prone even though it is extremely accurate compared to transcription and protein synthesis. Students need to understand some, but not all, of the DNA repair mechanisms and their intrinsic error rates. They should be able to understand overall error rates in different species and the implications for understanding evolution.

The basic biochemistry of recombination is an essential concept.

Teachers should avoid using the term "higher eukaryotes" and any other descriptions of species using the words "higher" and "lower."

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Tansey, J.T., Baird, T., Cox, M.M., Fox, K.M., Knight, J., Sears, D. and Bell, E. (2013) Foundational concepts and underlying theories for majors in “biochemistry and molecular biology”. Biochem. Mol. Biol. Educ., 41:289–296. [doi: 10.1002/bmb.20727]