1. Structure of DNA

4. DNA (deoxyribonucleic acid) is a nucleic acid, a macromolecule that stores information.
It consists of individual units called nucleotides which have three components: a molecule of sugar, a phosphate group (containing four oxygen atoms bound to a phosphorous atom), and a nitrogen-containing molecule called a base.
The physical structure of DNA is frequently described as a “double helix.”
What exactly is a double helix?
Picture a long ladder twisted around like a spiral staircase and you’ll have a good idea of what a DNA molecule looks like (Figure 5-4 Overview of the structure of DNA).
The molecule has two distinct strands, like the vertical sides of a ladder.
These are the “backbones” of the DNA molecule and each is made from two alternating molecules: a sugar, then a phosphate, then another sugar, then a phosphate, and so on.
The sugar is always deoxyribose, and the phosphate molecule is always the same, too.
It is the shapes of the backbone molecules that cause the DNA “ladder” to twist.

5. (Figure 5-6 The genome unpacked).
The full set of DNA present in an individual organism is called its genome.
In prokaryotes, including all bacteria, the information is contained within circular pieces of DNA.
In eukaryotes, including humans, this information is laid out in long linear strands of DNA. Rather than having the genome contained in one super-long DNA strand, eukaryotic DNA exists as numerous smaller, more manageable pieces, called chromosomes.
Humans, for example, have three billion base pairs, divided into 23 unique pieces of DNA (and we have two copies of each piece: one from our mother and one from our father, for a total of 46 chromosomes and six billion base pairs in every cell).

6. Each gene is the instruction set for producing one particular molecule, usually a protein.
For example, there is a gene that codes for fibroin, the chief component of silk.
And, there is a different gene that codes for triacylglyceride lipase, an enzyme that breaks down dietary fat.
Within a species, individuals sometimes have slightly different instruction sets for a given protein and these instructions can result in a different version of the same trait.
These alternate versions of a gene that codes for the same character are called alleles (Figure 5-7 “Different versions of the same thing”).
And any single feature of an organism is referred to as a trait.
A simple hypothetical example will clarify the meaning of these terms: The color of a daisy’s petals is a trait.
The instructions for producing this trait are found in a gene that controls petal color.
However, this gene may have many different alleles; one allele may specify the trait of red petals, another may specify white petals, and yet another may specific yellow petals.
Similarly, one allele for eye color in fruit flies may carry the instructions for producing a red eye, while another slightly different allele may be the instructions for brown eyes.

7. Not all DNA contains instructions for making proteins.
Why doesn’t that make an amoeba more complex than a human?
It is debatable whether humans are the most complex species on the planet, but surely we must be more complex than an onion.
But we’re not if you measure complexity by the amount of DNA an organism has: an onion has more than five times as much DNA as a human (Figure 5-8 Is the size of an organism’s genome related to its complexity).
We don’t fare any better when compared to some other seemingly simple organisms, either.
The salamander species Amphiuma means, for example, has about 25 times as much DNA as we do, and one species of amoeba—a single-celled organism—has almost 200 times as much! 7

8. The Proportion of the DNA That Codes for Genes: Just because we don’t yet know it’s function doesn’t mean non-coding DNA has no function.
The description in the first part of this chapter about what DNA is and how genes code for proteins is logical and tidy, but it doesn’t completely explain what we observe in cells.
In humans, for example, genes make up less than 5% of the DNA (Figure 5-9 “Junk DNA”?).
In many species, the proportion of the DNA that codes for genes is even smaller.
In virtually all eukaryotic species, the amount of DNA present far exceeds the amount necessary to code for all of the proteins present in the organism.
The fact is, a huge proportion of base sequences in DNA do not code for anything and has no obvious purpose. Many biologists even call it “junk DNA.”
In what types of organisms do we find the most “junk DNA”?
Bacteria and viruses tend to have very little non-coding DNA; with genes making up 90% or more of their DNA.
It is in the Eukaryotes (with the exception of yeasts) that we see the explosion in the amount of non-coding DNA, about 25% of which occurs within genes and 75% of which occurs between genes (Figure 5-10 Non-coding regions of DNA). 8

9. Figure 5-10 Non-coding regions of DNA.

11. RNA

12. How does a gene (a sequence of bases within a section of DNA) affect a flower’s color or the shape of a nose or the texture of a dog’s fur (the phenotype)?
The process occurs in two main steps: transcription, in which a copy of a gene’s base sequence is made, and translation, in which that copy is used to direct the production of a protein.
Figure 5-11 (Overview of the steps from gene to genome) presents an overview of the processes of transcription and translation.
In transcription, which occurs in the nucleus in eukaryotes, the gene’s base sequence or code is copied into a middle-man molecule called mRNA.
This is like copying the information for the chocolate chip cookie recipe out of the cookbook and onto a piece of paper.
In translation, the mRNA moves out of the nucleus and into the cytoplasm of the cell where the messages encoded in the mRNA molecules are used to build proteins.

13. In transcription, a single copy of one specific gene within the DNA is made.
Continuing our cookbook analogy, transcription is like copying a single recipe from the cookbook onto an index card.
It happens in four steps (Figure 5-12 Transcription: copying the base sequence of a gene).
Step 1 – Recognize, Bind, and Unwind: To start the transcription process, a large molecule, the enzyme RNA polymerase, recognizes a promoter site, a part of the DNA molecule that indicates the start of a gene, and, in effect, tells the RNA polymerase to “Start here.” At the promoter site, the molecule binds to one strand of the DNA and, like a court reporter transcribing everything that is said in a courtroom, begins to read the gene’s message. At the point where the RNA polymerase binds to the promoter, the DNA molecule unwinds just a bit, so that only one strand of the DNA can be read.
Step 2 – Transcribe - As the DNA strand is processed through the RNA polymerase, the RNA polymerase builds a copy—called a “transcript”—of the gene from the DNA molecule. This copy is called messenger RNA (mRNA) because once the copy of the gene is created, it can move elsewhere in the cell and its message can be translated into a protein.
The mRNA strand is constructed from four different molecules called ribonucleotides (which are almost identical to DNA nucleotides, consisting of a sugar-phosphate complex with a nitrogen-containing base attached), each of which pairs up with an exposed base on the now unwound and separated DNA:
If the DNA strand has a Thymine (T), an Adenine (A) is added to the mRNA.
If the DNA strand has a Adenine (A), a Uracil (U) is added to the mRNA.
If the DNA strand has a Guanine (G), a Cytosine (C) is added to the mRNA.
If the DNA strand has a Cytosine (C), a Guanine (G) is added to the mRNA.
Because our court reporter transcribes a specific sequence of DNA letters (the gene), the mRNA transcript carries the DNA’s information. And because it is separate from the DNA, the mRNA transcript can move throughout the cell, to the places where the information is needed, while leaving the original information within the DNA.
Step 3 – Re-wind: As the RNA polymerase moves down the unwound strand of DNA, the DNA that has already been transcribed twists back into its original double-helix form.
Step 4 – Terminate: When the RNA polymerase encounters a sequence of bases on the DNA at the end of the gene (called a termination sequence), the court reporter molecule stops creating the transcript and detaches from the DNA molecule. At that point, the mRNA molecule is released as a free-floating single-strand copy of the gene.
In prokaryotic cells, once the mRNA transcript separates from the DNA it is ready to be translated into a protein.
In most eukaryotes, however, the transcript must first be edited in several ways.
First, a cap and a tail may be added at the beginning and end of the transcript.
Like a front and back cover to a book, these serve to protect the mRNA from damage and help the protein-making machinery recognize the mRNA.
Second, because (as we saw in the previous section) there may have been non-coding bits of DNA transcribed, those sections—the introns—are snipped out.
Once the mRNA transcript has been edited, it is ready to leave the nucleus for the cytoplasm where it will be translated into a protein. 13

14. Several ingredients must be present in the cytoplasm for translation to occur.
First, there must be large numbers of free amino acids floating around.
Recall from Chapter 2 that amino acids are the raw materials for building proteins and an essential component of our diet.
Second, there must be molecules called ribosomal subunits, the moving protein-production factories where amino acids are linked together in the proper order to produce the protein specified by the mRNA transcript of the gene.
Finally, there must also be molecules that can read and translate the mRNA code from a base sequence into a protein.
These molecules, called transfer RNA (tRNA), are the interpreters of the mRNA code, linking specific bases on the mRNA with specific amino acids.
Because they play such a central role in translation, we examine them more closely. 14

16. Translation occurs in three steps (Figure 5-14 Translation: reading a sequence of nucleotides and producing protein).
Step 1 – Recognize and Initiate Protein-Building: Translation begins in the cell’s cytoplasm when a ribosome, essentially a two-piece protein-building factory, recognizes and assembles around a “start sequence”—which is always the bases A, U, and G next to each other—on the mRNA transcript. As the ribosomal subunits assemble themselves into a ribosome, one side of a tRNA molecule also recognizes the start sequence and binds to the mRNA at that point. That initiator tRNA has the amino acid methionine bound to its other side. This will be the first amino acid in the protein that is to be produced (although occasionally in eukaryotes it is edited out).
Step 2 - Elongate: After the mRNA start sequence, the next three bases on the mRNA specify which amino-acid-carrying tRNA molecule should bind to the mRNA next. If the next three bases on the mRNA transcript are GUU, for example, a tRNA molecule that recognizes that sequence will attach to the mRNA at that point. The GUU-recognizing tRNA molecule always has the amino acid valine attached. The ribosome then facilitates the connection of this second amino acid to the first.
The process continues in the same manner. The next three bases on the mRNA specify the next amino acid to be added to the first two. And the three bases after that specify the fourth amino acid and so on. This is the beginning of protein synthesis because all proteins are chains of amino acids, like beads on a string.
The mRNA continues to be “threaded” through the ribosome, with the ribosome moving down the mRNA strand reading and translating its message in little three-base chunks. Each three-base sequence specifies the next amino acid, lengthening the growing amino acid strand. After the amino acid carried by a tRNA molecule is attached to the growing protein, the tRNA molecule detaches from the mRNA and floats away.
Step 3 - Terminate: Eventually, the ribosome arrives at the three-base sequence on the mRNA that signals the end of translation. Once the ribosome encounters this sequence, the assembly of the protein is complete. Translation ends and the amino acid strand and mRNA molecule are released from the ribosome. When it is complete, the protein—such as insulin or a digestive enzyme—may be used within the cell or packaged for delivery via the bloodstream to somewhere else in the body where it is needed.
Following the completion of translation, the mRNA strand may remain in the cytoplasm to serve as the template for producing another molecule of the same protein.
In bacteria an mRNA strand may last from a few seconds to more than an hour; in mammals, mRNA may last several days.
Depending on how long it lasts, the same mRNA strand may be translated hundreds of times.
Eventually, it is broken down by enzymes in the cytoplasm. 16

18. Sickle-cell hemoglobin
Mutant hemoglobin DNA
mRNA
mRNA
Normal hemoglobin
Sickle-cell hemoglobin
Glu
Val
Figure 10.21

19. Met Lys Phe Gly Ala Met Lys Phe Ser Ala
Figure 10.22a

20. Mutations generally fall into two types: point mutations and chromosomal aberrations (Figure 5-16 Point mutations and chromosomal aberrations). In point mutations, one base pair is changed, whereas in chromosomal aberrations, entire sections of a chromosome are altered.
Point mutations are mutations in which one nucleotide base pair in the DNA is replaced with another or in which a base pair is inserted or deleted. Insertions and deletions can be much more harmful than substitutions because they can alter the reading-frame for the rest of the gene. Remember that the amino acid sequence of a protein is determined by reading the bases on an mRNA molecule three at a time and attaching the specific amino acid that is specified by that sequence. If a single base is added or removed, the three-base groupings get thrown off and the sequence of amino acids stipulated will be all wrong. It’s almost like putting your hands on a computer keyboard, but offset by one key to the left or right, and then typing what should be a normal sentence. It comes out as gibberish.
Chromosomal aberrations are changes to the overall organization of the genes on a chromosome. Chromosomal aberrations are like the manipulation of large chunks of text within a paper. They can involve the complete deletion of an entire section of DNA, the moving of a gene from one part of a chromosome to another, or the duplication of a gene with the new copy inserted elsewhere on the chromosome. In any case, a gene’s expression—the production of the protein the gene’s sequence codes for—can be altered when it is moved, as can the expression of the genes around it. 20

21. Mutations generally fall into two types: point mutations and chromosomal aberrations (Figure 5-16 Point mutations and chromosomal aberrations). In point mutations, one base pair is changed, whereas in chromosomal aberrations, entire sections of a chromosome are altered.
Point mutations are mutations in which one nucleotide base pair in the DNA is replaced with another or in which a base pair is inserted or deleted. Insertions and deletions can be much more harmful than substitutions because they can alter the reading-frame for the rest of the gene. Remember that the amino acid sequence of a protein is determined by reading the bases on an mRNA molecule three at a time and attaching the specific amino acid that is specified by that sequence. If a single base is added or removed, the three-base groupings get thrown off and the sequence of amino acids stipulated will be all wrong. It’s almost like putting your hands on a computer keyboard, but offset by one key to the left or right, and then typing what should be a normal sentence. It comes out as gibberish.
Chromosomal aberrations are changes to the overall organization of the genes on a chromosome. Chromosomal aberrations are like the manipulation of large chunks of text within a paper. They can involve the complete deletion of an entire section of DNA, the moving of a gene from one part of a chromosome to another, or the duplication of a gene with the new copy inserted elsewhere on the chromosome. In any case, a gene’s expression—the production of the protein the gene’s sequence codes for—can be altered when it is moved, as can the expression of the genes around it. 21