10.2: How A Cell Makes Protein

DNA can be likened to a huge recipe book bolted in a safe with its 20,000 valuable recipes. When a certain recipe is needed, a copy is made and taken to the chef. In DNA, the recipes are for proteins.

Copying and Delivering the Recipe

To make the protein insulin, for example, the first step is to make a copy of the gene (the recipe) for insulin. The two strands of DNA pull apart at the gene’s precise location so it can be copied (Figure 10.3).

Using the sequence of bases as a template, a matching copy is made. This copy of the gene is messenger RNA† (mRNA), which goes to a ribosome—a protein-making factory. mRNA is a messenger in that it delivers the recipe from the cell nucleus (the safe) to a ribosome (the chef) in the cytoplasm (the kitchen). See Figure 10.3.

Figure 10.2: Duplication of DNA

Figure 10.3: Making Protein, Starting with the Gene for that Protein

^{†RNA (ribonucleic acid), like DNA (deoxyribonucleic acid), is made up of bases hooked to a chain of sugars. But the sugar chain in RNA is made of ribose; in DNA, the sugar is deoxyribose. Also, 1 of the 4 bases in RNA differs. RNA uses U instead of T to pair with A. The 2 pairs in RNA are A-U and G-C.}

Making the Protein

Messenger RNA threads through the ribosome* (Figure 10.3), which “reads” the sequence of bases in groups of 3 (3-letter words). Each of the 20 kinds of amino acids has its own 3-letter word(s) (Table 10-1). As the “words” are read, each amino acid called for connects to the growing chain of amino acids. The amino acids are carried by transfer RNAs (Figure 10.3).

Table 10-1: The Amino Acid Code (Genetic Code) of Messenger RNA

Amino acids differ in size, shape, and chemistry, so their sequence in the chain is crucial in determining how the chain twists and folds into the elaborate structure that is characteristic of that protein and its function.

Using the cake analogy, the chef is like a ribosome—the chef reads the recipe and makes the cake. The recipe determines whether the cake is Angel Food or Chocolate. Just as a cake leaves the chef’s hands when done, the protein leaves the ribosome when it’s “done.”†

^{*For their work in revealing the atomic structure and inner workings of the ribosome, Ana Yonath, Thomas Steitz, and Venkatraman Ramakrishnan shared a Nobel Prize in 2009.
†Protein synthesis is actually more complicated, with splicing of mRNA, later modifications in the amino acid chain, etc.}

DNA Analysis

The Human Genome* Project (1990-2003) was a huge international undertaking to determine the sequence of the 3 billion pairs of bases in human DNA. It began the revolutionary explosion in DNA-based information. Its first director was James Watson, who in 1953 (at age 25) with Francis Crick discovered DNA’s structure.**

Pharmacogenomics looks at a drug’s effectiveness based on a person’s DNA. A drug that cures some patients but seriously harms others isn’t approved for general use. But if the patients it helps can be singled out genetically, the drug can be approved for them specifically.

Personalized/Precision Medicine uses an individual’s DNA profile to optimize treatment. Long-term studies of diverse populations provide genetic, environmental, and health data to examine individual variability in preventing and treating a wide range of diseases.

Molecular Paleontology compares DNA of various species. The more the resemblance, the more recently they branched apart in their evolutionary development.

DNA Profiling/Fingerprinting has had a huge impact on criminal justice. An early method is shown in Figure 10.4. Even DNA from a bit of tissue under a victim’s fingernail can provide incriminating evidence. To get enough DNA, trace amounts can be increased billions-fold by PCR (Polymerase Chain Reaction, Figure 10.5).

Figure 10.4: Early Method of DNA Fingerprinting/Profiling

Figure 10.5: PCR (the Polymerase Chain Reaction)

DNA fingerprinting was first used to solve a murder in 1987. A girl in an English village was raped and killed. A “likely suspect” confessed— the crime was “solved.” But his father sought DNA testing to prove his son’s innocence. Semen DNA on the girl didn’t match his son’s, but did match semen DNA on a girl raped and killed 3 years earlier—the same man raped both girls. About 5000 men ages 17-34 who lived nearby or were nearby at the time, gave blood and saliva to find the DNA match. The real culprit (who had no prior criminal record) was identified.

Alec Jeffreys, the molecular biologist who did this DNA match-up, also identified, in 1992, the exhumed bones of Joseph Mengele, the “Angel of Death” of Auschwitz. The bone DNA was compared with DNA from Mengele’s son, who gave a blood sample when told that bones of his father’s dead relatives might be exhumed for their DNA.

In 1998, an 11-year-old girl was raped, stabbed, and killed in Germany. Blood DNA from a knife at the scene matched semen DNA taken from another 11-year-old girl raped in 1996. Police tested saliva from 16,400 local men, ages 18-30, and found the DNA match—a 30-year-old from a neighboring town.

The first person in the U.S. convicted of murder on the basis of DNA evidence raped and killed four women in 1987 in a series of break-ins. There were no witnesses. Semen DNA at the crime scenes matched his. He was convicted in 1988 and executed in 1994 at age 32.

In 1976-1983, an estimated 30,000 people “disappeared” in an Argentine military campaign to silence political opposition. They included children and pregnant women who were killed after giving birth.

Many of the youngest children, including newborns, were taken by military couples or sold. In 1977, the children’s grandmothers began marching every Thursday at the Plaza de Mayo in Buenos Aires, and formed the human rights organization Grandmothers of the Plaza de Mayo.

With the help of geneticist Mary-Claire King (then of the Univ. of Calif. Berkeley, and who discovered the “breast cancer gene” BRCA 1), they created the DNA database used to identify the missing. In 2019, Javier Darroux Mijalchuk became the 130th to be identified; he was 4 months old when his parents were abducted in Buenos Aires.

Comparing DNA to family members was used to identify victims of the 9/11 attack, and Osama bin Laden, and an American pilot who was killed in Vietnam in 1972 and was buried in the Tomb of the Unknown Soldier in 1984, and exhumed in 1998.

Blood and saliva are routinely collected from U.S. military personnel—DNA is a much better “dog tag.” DNA identification also has more mundane uses, e.g., checking for fraudulantly labeled fish fillets in stores and restaurants.

Genetic Genealogy combines DNA testing with traditional genealogy. Direct-to-consumer DNA testing has resulted in huge public databases that not only yield personal information (e.g., your biological father isn’t who you thought he was) but help solve criminal cases (the biggest breakthrough since DNA fingerprinting).

In 2018, Joseph DeAngelo was charged with 13 murders and 13 rapes that occurred between 1976 and 1986. A DNA profile created from DNA from one of the crime scenes was uploaded to GEDmatch to create massive family trees that identified him as a suspect. The crime-scene DNA was then matched with his DNA on a discarded straw in his garbage.

Barbara Rae-Venter* worked with many investigators to solve this and many other cold cases. She determined that a skeleton found in 1998 was of a half-Asian half-Caucasian boy. A Caucasian relative was identified who said a relative married a Korean woman and had a son. The wife’s unidentifed body had been found in 1998 with no known connection to the boy. The husband/father was identified in 2018 and confessed to killing his wife and son.

^{*A genome is an organism’s genetic material, e.g., a cat’s DNA is the cat genome.
**Watson, Crick, and Maurice Wilkens shared a Nobel Prize in 1962 for this discovery. Wilkens and Rosalind Franklin made the X-ray diffraction photos of DNA that gave Watson and Crick crucial information on DNA structure. Franklin died in 1958 at age 37 of ovarian cancer. Nobel Prizes aren’t given posthumously.
***Barbara Rae-Venter, a PhD biologist and retired patent attorney specializing in biotech, has been acclaimed world-wide for her revolutionary forensic method of merging DNA science and genealogy to find and identify people.}