What You Need to Know About Identifying the Gene's Substance

The classic question about what genes are made of comes up in virtually every intro biology course, usually around chapter 10 to 12 depending on the textbook. The short version: genes are made of DNA. But the actual material that led scientists to that conclusion involved a series of experiments that are worth going through in order, because each one ruled out a competing hypothesis. If you're just looking for an answer key, you'll find it below, but understanding the sequence matters more for exams than memorizing a list. Here's a straightforward answer key for the standard problems you'll see on this topic: 1. What organism did Griffith use? Streptococcus pneumoniae. He worked with rough (non-virulent) and smooth (virulent) strains in mice.

2. What was Griffith's key finding? A "transforming principle" from dead smooth bacteria could convert live rough bacteria into virulent smooth ones. He didn't know what the substance was, only that transformation happened. 3. Who identified the transforming principle as DNA? Avery, MacLeod, and McCarty in 1944. They treated extracts with proteases, RNases, and DNases, showing that only DNase destroyed transforming activity. 4. Why was their work initially met with skepticism? Many researchers still believed proteins were the genetic material because proteins are structurally more complex with 20 amino acids versus DNA's four nucleotides. It took additional evidence to change minds.

5. What did the Hershey-Chase experiment demonstrate? Using radioactive sulfur-35 (marks proteins) and phosphorus-32 (marks DNA), they showed that only DNA entered bacterial cells during phage infection. Proteins stayed outside. 6. What was Chargaff's contribution? He found that in DNA, the amount of adenine equals thymine, and guanine equals cytosine. This base-pairing rule became essential for the double helix model. 7. What did Rosalind Franklin's Photo 51 reveal? It showed an X-shaped diffraction pattern consistent with a helical structure, and allowed calculation of the helix diameter and repeat distances.

8. What model did Watson and Crick build from this data? The double helix with antiparallel strands held together by hydrogen bonds between complementary bases. 9. How does DNA replication work based on this? Semiconservative: each new molecule contains one original strand and one newly synthesized strand. Meselson and Stahl proved this in 1958 using nitrogen isotope labeling. 10. What enzyme is primarily responsible for building new DNA strands? DNA polymerase, which adds nucleotides in the 5' to 3' direction.

I ran into a specific issue when grading papers on this topic. Students consistently confused the Avery-MacLeod-McCarty experiment with Hershey-Chase. They'd attribute the radioactive isotope work to Avery, which is wrong on two levels. The workaround I started using is making students draw a timeline with dates attached to each experiment. 1928 Griffith, 1944 Avery et al., 1952 Hershey-Chase, 1953 Watson-Crick, 1958 Meselson-Stahl. When they have to place the dates, the confusion collapses pretty quickly.

Common Pitfalls That Cost Points

The most frequent mistake I see is calling the transforming principle a "gene" before the concept was established. Griffith called it a transforming principle. The word gene existed but the physical substance was still unknown. Saying Griffith identified the gene's substance is anachronistic. Another one: students often state that Franklin and Watson/Crick worked together. They didn't. Franklin's data was shared without her knowledge. She produced the X-ray diffraction image independently at King's College, and Wilkins showed it to Watson. This matters for understanding the actual history, even if the exam question doesn't ask about it directly. A counter-intuitive point that trips people up: Chargaff's rules apply to double-stranded DNA but not single-stranded DNA. Some viruses have ssDNA genomes, and in those cases A does not equal T. If a question mentions bacteriophage X174, Chargaff's rules don't hold. That's a detail most textbooks gloss over.

Limitations of This Material

The traditional narrative I just outlined is clean and pedagogical, but it leaves out important context. For one, the prion controversy of the 1980s and 1990s showed that infectious agents can exist without nucleic acids at all. Prions are misfolded proteins that transmit their conformation. This doesn't change the fact that genes are made of DNA or RNA, but it does mean the older idea that "genetic material must be self-replicating chemistry" has edge cases worth knowing about. Additionally, the Hershey-Chase experiment has a flaw that advanced courses sometimes highlight. A small percentage of phage protein does enter the bacterial cell during infection, but it's not the genetic material. Purists argue this means the experiment isn't as clean as introductory texts make it seem. The conclusion still stands, but the evidence is slightly messier than the simplified version suggests. If you need to supplement this material, I'd recommend looking at the original Avery paper from 1944 in the Journal of Experimental Medicine. It's surprisingly readable. For the Hershey-Chase work, the 1952 Journal of General Physiology paper is short and to the point. Both are available through most university libraries or through PubMed Central.