In the long history of genetics – and of our teaching about it – “mutation” generally has been defined as any change in DNA sequence. In addition, as the other guest editorial in this issue (“What’s in a Name: Mutation versus Variant?” by Garry Cutting) points out, the term “mutation” generally has carried a “negative connotation,” one that implies a phenotype that is somehow deficient. Next-generation genome sequencing, however, requires that we rethink our approach to the vocabulary we employ in the classroom when we address these concepts.
Massively parallel DNA sequencing has increased tremendously our ability to elaborate biological variation at the level of individual bases. How should we categorize for our students the immense number of changes in DNA sequence, irrespective of species, that have no discernible biological impact or whose effects are yet unexplored? Certainly, as Dr. Cutting points out, not all of these changes will have negative consequences for the individual organisms in which they reside.
References to mutation and variation appear several times in the Next Generation Science Standards at the high school level. For example,
Life science standard 3-2: “Make and defend a claim based on evidence that inheritable genetic variations may result from: (1) new genetic combinations through meiosis, (2) viable errors during replication, and/or (3) mutations caused by environmental factors.”
Life science standard 4-2: “Construct an explanation based on evidence that the process of evolution primarily results from four factors (including) … The inheritable genetic variation of individuals and species due to mutation and sexual reproduction….”
Note the potential in these standards to equate genetic variation with mutation, an unwise conflation in Dr. Cutting’s view. We can avoid this confusion by distinguishing process from impact, to wit: the process of mutation is the root source of all genetic variation, whereas the downstream effect of the process – the impact – is highly dependent on a number of interacting variables.
Standard 4-2 provides some assistance with this distinction by placing variation and mutation in an evolutionary context. Using this lens, the instructor can emphasize the variable impact of genetic changes – beneficial, harmful, or neutral – and invite students to suggest the appropriate designation for the change in question.
This newly evident need to differentiate between a variant and a mutation also provides an opportunity to address standards related to the nature of science (e.g., “Scientific Knowledge Is Open to Revision in Light of New Evidence”). Perhaps the most germane high school standard in this category is the following: “Most scientific knowledge is quite durable but is, in principle, subject to change based on new evidence and/or reinterpretation of existing evidence.” Nothing in the rapid accretion of sequence data challenges the durability, for example, of the chromosome theory of inheritance or our conception of DNA as the universal information molecule for life on earth. It does, however, require us to rethink the meaning of those data.
Finally, Dr. Cutting’s brief essay reminds us that precision in language is critical to the nature and methods of science. We do not enjoy Humpty Dumpty’s prerogative (i.e., “When I use a word it means just what I choose it to mean – neither more nor less”). The precision of our language reflects the quality of our thinking, and the words we choose to describe natural phenomena must make sense to our colleagues if they are to become part of our common vocabulary and prove useful in scientific inquiry.
I am grateful to Michael J. Dougherty for a helpful discussion about this editorial.