Genetics is perhaps the most rapidly growing field of science today. Recent findings such as those of the Human Genome Project have led to new understandings of basic genetic phenomena and even to increased confusion about some basic genetic ideas, such as the nature of the gene. These developments directly influence how we should teach genetics. This article considers eight claims typically made by introductory biology teachers and considers how they differ from current understandings.

A Quick Genetics Quiz

Take the quick true/false quiz in Table 1. Some may be tricky, so read carefully. Once you have answered an item, don’t go back to it because of what you read in a later item. (You will find the answers below. Don’t peek! No one is grading you.)

Table 1.

True/false quiz.

StatementTrueFalse
1. A gene is a segment of DNA that codes for a polypeptide.   
2. Genes determine the phenotype of an organism.   
3. The environment has a minor effect on most traits.   
4. A garden pea with the TT genotype will be tall.   
5. Most traits are determined by a single gene.   
6. A few traits are determined by many genes.   
7. Every individual has two genes for each trait.   
8. In Mendel’s peas, the letter T stands for the gene for tall; t is the gene for short.   
StatementTrueFalse
1. A gene is a segment of DNA that codes for a polypeptide.   
2. Genes determine the phenotype of an organism.   
3. The environment has a minor effect on most traits.   
4. A garden pea with the TT genotype will be tall.   
5. Most traits are determined by a single gene.   
6. A few traits are determined by many genes.   
7. Every individual has two genes for each trait.   
8. In Mendel’s peas, the letter T stands for the gene for tall; t is the gene for short.   

Surprisingly, all these statements are FALSE in one way or another!

As teachers, we sometimes make mistakes. It’s sad, but true. We do so for lots of reasons. Sometimes we use words loosely – we know what we mean as biologists, but the students don’t and may get confused. Sometimes we say things that are based on our own misunderstandings or misconceptions (for an excellent compilation of identified misconceptions related to genetics, see Shaw et al., 2008). And sometimes, of course, our understanding is out of date. Genetics is one of those fields in which the science is moving so fast that even the textbooks include explanations that are as old as “your father’s Oldsmobile” – or even your grandmother’s! In the past few years, a perfect storm of new technology and research, including the Human Genome Project, has produced a conceptual and technological revolution that has drastically changed our understandings of genetics and heredity. This article addresses some examples of these changes that biology teachers need to know. Each incorrect statement is presented in bold below, followed by an explanation and proposed replacement language.

1. A gene is a segment of DNA that codes for a polypeptide.

This statement is false in a simple way that many teachers know about, but it is also incorrect because of recent discoveries in genetic science. It has been known for some time that genes in eukaryotic organisms are composed of coding regions (called “exons”) interspersed with noncoding regions (called “introns”). The entire DNA segment is typically transcribed, and the introns are removed (or “spliced out”) by structures called “spliceosomes.” So a gene is not a simple segment of DNA, at least not a continuous one.

More recently, several other surprising gene structures have been found. The Human Genome Project’s studies have shown that DNA that codes for individual proteins is often split and scattered throughout the genome (see Silver, 2007); parts of the sequence of a single gene are found on different strands, are located far apart on the same chromosome, or may even be found on different chromosomes entirely! Consider, for example, the human gene that encodes the blood-clotting protein factor VIII, which spans ~186 kb of DNA and is divided into 26 exons (Cooper & Hausman, 2000). Different proteins can even be produced from different reading frames of the same DNA sequence, as shown by the fact that the HIV genes gag, pol, and env are read in the three different reading frames of the single genomic RNA molecule, sometimes even in overlapping segments (see Figure 1).

Figure 1.

Landmarks of the HIV-1 genome, HXB2 strain. Open reading frames are shown as rectangles. The gene start, indicated by the small number in the upper left corner of each rectangle, normally records the position of the a in the ATG start codon for that gene, while the number in the lower right records the last position of the stop codon. For pol, the start is taken to be the first T in the sequence TTTTTTAG, which forms part of the stem loop that potentiates ribosomal slippage on the RNA and a resulting −1 frameshift and the translation of the Gag-Pol polyprotein. The tat and rev spliced exons are shown as shaded rectangles. In HXB2, *5772 marks the position of frameshift in the vpr gene caused by an “extra” T compared to most other subtype B viruses; !6062 indicates a defective ACG start codon in vpu; †8424 and †9168 mark premature stop codons in tat and nef. Taken from Los Alamos National Laboratory, 2012: http://www.hiv.lanl.gov/content/sequence/HIV/MAP/landmark.html. Used with permission.

Figure 1.

Landmarks of the HIV-1 genome, HXB2 strain. Open reading frames are shown as rectangles. The gene start, indicated by the small number in the upper left corner of each rectangle, normally records the position of the a in the ATG start codon for that gene, while the number in the lower right records the last position of the stop codon. For pol, the start is taken to be the first T in the sequence TTTTTTAG, which forms part of the stem loop that potentiates ribosomal slippage on the RNA and a resulting −1 frameshift and the translation of the Gag-Pol polyprotein. The tat and rev spliced exons are shown as shaded rectangles. In HXB2, *5772 marks the position of frameshift in the vpr gene caused by an “extra” T compared to most other subtype B viruses; !6062 indicates a defective ACG start codon in vpu; †8424 and †9168 mark premature stop codons in tat and nef. Taken from Los Alamos National Laboratory, 2012: http://www.hiv.lanl.gov/content/sequence/HIV/MAP/landmark.html. Used with permission.

Moreover, neither the exon–intron structure nor the phenomenon of splicing of transcripts is unusual or unimportant, like some exception to the rule; Human Genome Project findings suggest that >5% of all human genes code for transcription factors, which are involved in initiation and splicing (Moss, 2004), and some 60% of our exons are subject to splicing and resorting (Keller & Harel, 2007).

Findings like these have made the very definition of the gene an incredibly complex issue in recent years, resulting in much disagreement among geneticists. (For more on this issue, see Smith & Adkison, 2010). There is now considerable disagreement about exactly how to define the term gene, and what language to use as a replacement for statement 1 is unclear. One approach is to use the definition presented in your course textbook but also note the deficiencies in that definition.

2. Genes determine the phenotype of an organism.

3. The environment has a minor effect on most traits.

Today we know that the gene is not the sole, or perhaps even the primary, determiner of most traits. Genes and their products are modified or controlled (turned on or off) by other genes, by the context/environment (cytoplasm) they find themselves in, by the environment of the cell and eventually by that of the organism. Early in the history of genetics, there were two camps among those interested in the study of heredity: those who would come to be called “geneticists,” who focused on the primary importance of the genetic material in the chromosomes; and the “developmentalists,” who focused on the importance of everything else in determining phenotype (Moss, 2004). Of course, the geneticists won out. But genetics has now come full circle; we are just now recognizing the importance of the environment and everything else “above” the DNA level for producing the final organism phenotype. We call the study of these effects “epigenetics.” Therefore, genes today are not seen as determiners of traits (a view labeled “deterministic”) but as only one component (albeit a very important component) of a complex set of chemicals and processes that, together, determine the phenotype. This more recent view expands genetics into “genomics.”

Take, for example, the human trait of spina bifida, a condition in which the spinal cord and the surrounding layers (including the vertebrae) do not close properly in development, and the spinal cord of the resulting child is open to the outside on the surface of the back (Figure 2). (Technically, I am speaking here about one of several forms of spina bifida, called “meningomyelocele.”) Spina bifida is known to be common in some families and, thus, is assumed to be determined largely by genetics. If pregnant women regularly take a vitamin A supplement very early during pregnancy, however, many of these abnormal births are prevented. Thus, today we recommend that all women who might become pregnant (whether planned or not) should take regular doses of vitamin A, and the incidence of spina bifida has been reduced greatly.

Figure 2.

Spina bifida (open defect). Image courtesy of the Centers for Disease Control and Prevention (http://www.cdc.gov/ncbddd/spinabifida/facts.html). Used with permission.

Figure 2.

Spina bifida (open defect). Image courtesy of the Centers for Disease Control and Prevention (http://www.cdc.gov/ncbddd/spinabifida/facts.html). Used with permission.

The point is that the genetics of the child born with spina bifida does not determine the phenotype, at least not solely. The phenotype also depends on the environment of the fetus. The fetal phenotype can be normal if it was exposed to an increased concentration of vitamin A from the mother’s blood. The phenotype is determined by both the genetics and the environment. We call such traits “multifactorial” (i.e., they are determined by multiple factors).

Some have likened the gene to a recipe. The recipe does not “make” the cake or cookie. The chef uses spoons and bowls and ovens in the process. She may choose to substitute an ingredient, add pecans, or increase the amount of chocolate chips. She may choose to make soft-baked cookies today and hard-baked cookies tomorrow. She may make mistakes. The cookies may turn out differently when the recipe is followed at a high altitude rather than at sea level. She may decorate the cookies with sprinkles or use different cookie cutters to make different shapes. The same cake-batter recipe can be used to make a wedding cake or a birthday cake for a three-year-old. And so it is with what happens from the process of transcription to the expression of the phenotype.

We have, of course, long recognized the importance of environmental factors (e.g., learning and nutrition), often phrased as “nature versus nurture,” but recent genetics has shown that the environment plays a much more central role than we have implied. The phenotype is not determined by nature (the genes) and merely tweaked by nurture. We now know that “the [DNA] molecule can’t dance without a team of choreographers, that it comes alive only when numerous proteins pull its ‘string’” (Keller & Harel, 2007, p. 2).

Recent writers have likened the situation to asking whether the drumming sound we hear is made by the drum or the drummer (Figure 3). Is the area of a rectangle due more to its length or its width? (For a review, see Keller, 2010.) The question itself is, of course, nonsensical. Phenotypic traits are “co-constructed” during development by genetic and environmental factors operating together in collaboration with one another; the two are ‘interdependent’” (Moore, 2008, pp. 332, 342).

Figure 3.

Drums and drummer. Used with permission.

Figure 3.

Drums and drummer. Used with permission.

As Keller (2010) puts it,

We have learned for instance that the causal interactions between DNA, proteins, and trait development are so entangled, so dynamic, and so dependent on context that the very question of what genes do no longer makes much sense. (p. 58)

In the simplest terms, “All traits are 100% genetics as well as 100% environmental: drum and drummer” (Falk, 2014, p. 281).

Replacement Language

An organism’s DNA sequence is transformed into an RNA sequence that may then be transcribed into an amino acid sequence in a polypeptide which is part of a complex set of chemicals and processes that co-construct the phenotype.

Most traits in human and other complex organisms are multifactorial – determined both by genetics and by the environment.

4. A garden pea with the TT genotype will be tall.

Part of the story of recognizing the importance of epigenetics is, again, that the genes are not the whole story. The TT pea plant has the capacity to be tall (Figure 4), but any number of other factors involved could result in the plant not being tall (consider, for example, the availability of sun, moisture, and nutrients). In fact, when the tt plants are supplemented with gibberellin (the hormone not produced by these plants), the plants will grow to be tall (Lester et al., 1997; Offner, 2011). These factors account for variability in the plant’s phenotype.

Figure 4.

Scientist with tt cabbage plants supplemented with gibberellin. Used with permission.

Figure 4.

Scientist with tt cabbage plants supplemented with gibberellin. Used with permission.

Geneticists sometimes refer to two ways that the phenotype can vary, using the terms expressivity and penetrance. Any two TT plants are not, of course, the exact same height; there is variability in how each genotype is “expressed” in the final phenotype (“variable expressivity”). On the other hand, in most human disorders (especially dominant ones), a person may carry the genotype for a disorder but not have the mutant phenotype; the mutant allele has not “penetrated” to that level (“reduced penetrance”).

Once on genetics hospital rounds, we saw a couple with a child who had been diagnosed with achondroplasia, a condition that causes a form of dwarfism. The presenting resident told the group that the condition had to be recessive because neither of the parents was of short stature, but I knew that the disorder is typically inherited as a simple Mendelian dominant. Like so many students, the resident had not taken into account that penetrance is not always 100%. A very large proportion of those who carry the (dominant) mutant allele associated with this form of dwarfism are not short (i.e., achondroplasia shows reduced penetrance). Many teachers may discuss penetrance and expressivity briefly, but all too often our instruction wrongly implies that penetrance is always 100% (as it is in Mendel’s traits in peas).

Some traits can show both variable expressivity and reduced penetrance. Personally, I have a dominant genetic disorder known as Charcot-Marie-Tooth (CMT) syndrome, a progressive distal neuropathy characterized by the decreasing rate at which neural impulses pass along the long nerves of the body (Figure 5). CMT can cause stumbling (from muscle weakness), poor balance, loss of awareness of the position of feet (reduced proprioception), loss of coordination (imagine my poor handwriting!), and severe pain in the hands and feet, but no decrease in life expectancy. My brother has been tested and is known to carry the (dominant) allele, but he has none of these symptoms (if you ignore his questionable handwriting!). I have all these symptoms to some degree, as does my sister. We all carry the same CMT allele, which obviously has reduced penetrance. In addition, my sister’s symptoms are much more severe than mine. Therefore, our CMT allele (which we all inherited from my affected mother) also shows variable expressivity. Phenotypic expression of many human traits is similar to that of CMT. If students are to understand human inheritance, they need to understand that reduced penetrance and variable expressivity are common phenomena.

Figure 5.

My foot, showing high arc (pez cavus) typical of a person with CMT.

Figure 5.

My foot, showing high arc (pez cavus) typical of a person with CMT.

Replacement Language

A garden pea with the TT genotype has the capacity or potential to be tall.

An organism’s genetics determines its capacity for expressing a trait; the environment determines the extent to which that capacity is expressed.

5. Most traits are determined by a single gene.

6. A few traits are determined by many genes.

Introductory biology textbooks typically spend most of the genetics chapter telling about Mendel and explaining his experimental results (Figure 6). They give much less attention to “non-Mendelian” traits (e.g., sex linkage and multiple alleles) and even less specific attention to phenotypes that are affected by two or more genes (a phenomenon called “polygeny”) or those determined by an interaction of the gene(s) and the environment (“multifactorial inheritance,” discussed above). Not surprisingly, students get the mistaken notion that most inheritance is so-called “Mendelian” (i.e., determined by a single gene – sometimes called “monogenic” – that has only two alleles). This is not true. At least for more advanced species, from fruit flies to humans, most traits are both polygenic and multifactorial and have multiple alleles. It is the “all or none” Mendelian traits that are the exception!

Figure 6.

Mendel’s experiment 1. Used with permission.

Figure 6.

Mendel’s experiment 1. Used with permission.

And the polygenic and multifactorial determination of phenotype is not just a complicated explanation that only geneticists need to understand. Heart disease, cancer, stroke, and diabetes – all these, and other, human conditions that will affect the lives of students and their families in the future are determined by multiple genes in conjunction with the environment (Dougherty, 2009).

Replacement Language

Most traits are polygenetic – determined by many genes.

7. Every individual has two genes for each trait.

As just noted, most traits are polygenetic and multifactorial, but there is another common error in statement 7. Geneticists (and genetics teachers) often use the terms gene and allele interchangeably. When you first read the sentence above, you probably “saw” it (maybe unconsciously) as “two alleles.” We know what we mean when we are sloppy with our language, but it can confuse students. This is a very common error, typical of even the most knowledgeable geneticists and genetics teachers. Pay attention every time you use these two words in the classroom, or tape record your lecture, or have another biology teacher sit in and note how you use these terms. You’ll likely be amazed at how easy it is to use these terms inconsistently. (For more on the use and meaning of the word allele, see Smith & Adkison, 2010)

Replacement Language

Every individual has two copies of each gene, found on homologous chromosomes. Different copies of a gene are called “alleles.”

8. In Mendel’s peas the letter T stands for the gene for tall; t is the gene for short.

As just noted, the word gene here should be replaced with the word allele, but there is another error here as well. Given what we know today about the importance of epigenetic factors in the production of the final phenotype, it is also a misleading overstatement (and considered largely incorrect) to describe any allele as “the allele for” a given trait. Both geneticists and genetics educators (and even biology textbooks) often use this very common convenient shorthand, but we must break ourselves of the habit of using such sloppy language. The “gene for” language is essentially another statement of genetic determinism.

The relative importance of the environment was understood by some of the earliest geneticists – well before the nature of genes was understood. Sturtevant (in 1915) noted: “Although there is little that we can say [at that time] as to the nature of Mendelian genes, we do know that they are not ‘determinants’” (Moore, 2008, p. 339; emphasis added).

It is important to discourage deterministic thinking among students both for the scientific reasons outlined above and for practical reasons. Genetic testing is likely to become more and more common in the immediate future. Even now, websites are available that promise, for a fee, to use “a little bit of spit” to determine a person’s likelihood of a multitude of human conditions, from your percentage of “Neanderthal ancestry” and your “HIV resistance” to high cholesterol and heart disease (https://www.23andme.com/). In the future, physicians will also make increasing use of DNA sequencing to guide diagnosis and treatment. Future citizens will need to be able to understand what the reports obtained from these services do and do not mean.

In order to address deterministic thinking in our students, of course, we must first purge it from our own minds and from our classroom talk. The next time you are discussing genes, notice how difficult it is to avoid use of any form of the word “determine.”

Regarding Mendel’s tall–short gene in particular, it is also important to remember that the Tt gene he studied codes for only one of several involved in a complex hormone-producing pathway (Lester et al., 1997; Offner et al., 2011). Thus, there is no single gene for height in peas; there are many. Pea height is polygenic. As noted above, height can also be modified by environmental factors; therefore, inheritance of pea height is also multifactorial.

Replacement Language

The allele designated by Mendel as T codes for tallness in the garden pea.

Summary

Once upon a time, maybe when your grandmother learned about genetics, we thought that genes “determined” the phenotype with little or no impact from the environment, and we largely ignored phenomena such as penetrance and expressivity. Defining the gene was simple because we thought that a gene was just a sequence of contiguous nucleotides in a single DNA molecule. Effects of the environment on the final phenotype were of little importance, and reduced penetrance and variable expressivity were exceptions and were not important for introductory genetic understanding. Our teaching focused almost exclusively on Mendelian traits, with little or no emphasis on polygenic and multifactorial inheritance, and students failed to appreciate that most traits are not Mendelian. “Genomics,” “epigenetics,” and “personalized medicine” based on the individual’s DNA were unheard of. As outlined above, things have changed! All these ideas have been modified or rejected, and teachers and textbooks need to catch up.

Our students live in a world of “personalized medicine” that will increasingly rely on genetic testing and risk assessment. A good understanding of genetics will be needed to function in this brave new world. The new world is the world of epigenetics, which recognizes that the genome alone does not “determine” the phenotype, that “it is not DNA that does things to the cell; rather, it is the cell that does things with DNA” (Meyer et al., 2013, p. 360).

What distinguishes one biological form from another is seldom, if ever, the presence or absence of a certain genetic template but rather when and where genes are expressed, how they are modified, and into what structural and dynamic relationships their products become embedded. (Moss, 2004, p. xvii)

The old “determinist” view that your grandmother may have learned – that there are genes “for” every trait, including height and spina bifida and even intelligence, homosexuality, aggression, and so on – is no longer valid. The hot issue in the field for the next few years will be how development of these and many other multifactorial traits occurs. Until those mechanisms are better understood, teachers must at least make it clear that the phenotype is co-constructed by a complex system that includes both the genome and the environment. As Moore (2008) notes, such instruction is important even though it may be difficult

to convince students to give up a [simple Mendelian] sense of understanding (however ill-founded it might be) in favor of a more honest sense of ignorance…. It is not particularly surprising that students would prefer deterministic theories to probabilistic theories. (p. 343)

Dougherty (2009) adds:

To pretend such uncertainty [lack of simple determination of the phenotype by DNA] does not exist is to deprive students of an appreciation off both modern genetics and the nature of science. (p. 8)

It is sometimes easy to forget that the study of genetics is little more than a century old – a young science that would be expected to grow rapidly. In addition, genetics has come of age at a time of exponential technological progress, resulting in an even more rapid rise in understandings. It is an exciting time to be a geneticist, a genetics teacher, or a genetics student. The growth in genetic understanding is changing our lives, especially our medical care, but the need to replace your “grandmother’s genetics” with up-to-date understandings places high demands on teachers.

Acknowledgments

I want to express my appreciation to Mark Swanson, Michael Dougherty, and Mark Terry, who provided useful feedback on the manuscript.

References

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