DNA

DNA Structure

In humans, DNA is a linear, double-stranded structure composed of multiple units of four different nitrogenous bases, each attached to a sugar molecule. The bases in each strand are linked together by phosphate groups. These two individual strands are held together loosely. This double-stranded DNA is arranged like a long set of railroad tracks. The “backbones” of the track are the two long steel rails. For DNA, these backbones are the phosphate groups that hold the bases in place. The bases are the individual railroad ties. Think of each tie as having two pieces—one piece attached to the right-hand rail and one piece attached to the left-hand rail.

Fig. 6-2 shows a very small piece of double-stranded DNA on the left (containing only four base pairs) taken from the larger piece of DNA on the right. The phosphate groups that hold the nucleotides together as a strand are in the red box. The green box in the lower left-hand section shows a whole nucleotide (a base with the sugar and the phosphate group) in place in the left-hand DNA strand. The blue box in the middle of the two strands shows how the base from the left strand lines up with and pairs to a complementary base in the right strand.

FIG. 6-2 The structure of DNA.

Bases are the essential parts of DNA. Many trillions of bases in the DNA are found in the nucleus of just one cell. In fact, if a cell could be cracked open like an egg and the nucleus (yolk) extracted and opened, the amount of DNA in the nucleus, stretched out, would be about 6 feet long. If the DNA in one cell could be made large enough to see and touch (about the width of a tape measure), it would be long enough to stretch out more than 1000 feet! There is much more DNA in each nucleus than is needed for the 25,000 genes. The gene DNA makes up only about 5% of all the DNA in each cell.

The four bases in DNA are adenine (A), guanine (G), cytosine (C), and thymine (T). Each base becomes a complete nucleotide when a five-sided sugar (known as a deoxyribose sugar) and a phosphate group are attached (Fig. 6-3). Nucleotides form the DNA strands with the phosphate groups holding the bases in place.

FIG. 6-3 Close view of DNA with four bases converted into nucleotides held loosely together by hydrogen bonds forming complementary base pairs. — — — = weak hydrogen bonds.

Base pairs are the linked bases in the two opposite strands of DNA. The bases always link together across from each other in a very specific way. Thymine always forms a pair with adenine, and cytosine always forms a pair with guanine. Thus the bases of each pair are complementary to each other. Because these complementary base pairs in DNA are specific, if the base sequence of one strand of DNA is known, the opposite strand’s sequence could be accurately predicted. For example, if the left-hand section of DNA (strand 1 in Fig. 6-4) had the sequence A-G-G-C-T-C-A-A-C-C-T-G, the corresponding (complementary) right-hand section (strand 2 in Fig. 6-4) of DNA would have the sequence T-C-C-G-A-G-T-T-G-G-A-C.

FIG. 6-4 Complementary strands of DNA.

When the two strands of DNA are lined up properly, they twist into a loose helical shape (see Fig. 6-1). In this shape, the DNA is so fine that it can be seen only with electron microscopes. Only when a cell begins to divide (i.e., undergoes mitosis) does the DNA super-coil tightly into dense pieces called chromosomes (see Fig. 6-1), which can be seen with standard microscopes.

DNA Replication

DNA must reproduce itself (replicate) every time a cell divides. Cell division (mitosis) occurs in a regulated pattern known as the cell cycle. The purpose of mitosis is for one cell to reproduce into two new cells, each of which is identical to the cell that started mitosis. For each new cell to have exactly the right amount of DNA and genes, the DNA in the dividing cell must exactly replicate. This process involves having the double strands of DNA separate and then enzymes read the sequence of the original strands and build two new strands that are perfectly complementary to the original strands (Fig. 6-5).

FIG. 6-5 DNA replication. Blue type, Original DNA; red type, newly replicated DNA.

When DNA synthesis is complete, the result is two sets of double-stranded DNA. Each of the two sets has one old strand and one new strand. At the time of actual cell division with the separation into two new cells, one set of DNA will move into one of the two new cells made during mitosis and the second set will move into the other new cell. In this way, every new cell ends up with exactly the right amount of DNA with all the genes.

Chromosomes

As shown in Fig. 6-1, a chromosome is a specific large chunk of highly condensed double-stranded DNA, with each chunk containing billions of bases and hundreds (and sometimes thousands) of genes. Each chromosome forms and moves to the center of the cell that is about to divide. Just before the cell splits into two cells, each chromosome is pulled apart so that half of each chromosome goes into one new cell and the other half goes into the other new cell. Thus chromosomes are temporary structures, but their job is important: precise delivery of DNA to the two new cells. Humans have 46 chromosomes divided into 23 pairs. This number is the “diploid” number of chromosomes for humans.

Fig. 6-6 shows a metaphase chromosome. The “pinched in” area of the chromosome is the centromere. Each left and right half of the chromosome is a chromatid. The “arms” above the centromere are the short arms, or the “p” arms. The longer arms (not legs) below the centromere are the “q” arms. A particular gene may be listed as located on 9q, meaning that the gene has its location (locus) on the long arm of the number 9 chromosome.

FIG. 6-6 A single metaphase chromosome.

Some things about a person can be known by examining his or her chromosomes. It is important to remember that the information that can be obtained by chromosomal analysis is limited because each chromosome is composed of a large chunk of DNA. Only very large deletions, additions, or rearrangements of DNA show up at the level of the chromosome. Losses or gains of just a few bases (or even tens of thousands) cannot be detected by chromosome analysis.

A karyotype is an organized arrangement of all of the chromosomes present in a cell during the metaphase section of mitosis (Fig. 6-7). A picture of the chromosomes is made. Chromosomes are first paired up and then arranged according to size (largest first) and centromere position. This gross organization of DNA can be used to determine missing or extra whole chromosomes and some large structural rearrangements. A missing gene or a mutated gene would not show up at this level of analysis. What can be learned about the person from whom the karyotype in Fig. 6-7 was made is that the person is human, female, and euploid (has the correct number of chromosome pairs for the species). This person is chromosomally “normal,” although she might have one or more genes that are mutated. If the karyotype is abnormal in any way (had more or less than the normal number or had broken chromosomes), the karyotype would be called aneuploid.

FIG. 6-7 A karyotype of a chromosomally normal female. (The sex chromosomes are circled in red.)

Autosomes are the 22 pairs of human chromosomes (numbered 1 through 22) that do not code for the sexual differentiation of a person. Autosomal chromosomes contain genes that code for all the structures and regulatory proteins needed for normal function. Sex chromosomes are the pair of chromosomes that include the genes for the sexual differentiation of the person. Chromosomally normal males have an X and a Y as the sex chromosomes. Chromosomally normal females have two XXs as the sex chromosomes (see Fig. 6-7).

Gene Structure and Function

A gene is a specific segment(s) of DNA that contains the code (recipe) for a specific protein (see Fig. 6-1). One gene usually codes for one protein; thus genes are the smallest functional unit of the DNA. Each chromosome contains hundreds of genes (and each chromosome is made up of a large segment of DNA). Thus an individual gene is a very small segment of DNA.

For many human traits, one gene controls the expression of that trait in any person. Such traits are known as “single gene traits” (monogenic traits). For each single gene, we have two alleles. An allele (pronounced “ah-lee-el”) is an alternate form (or variation) of a gene. For example, there is one gene for blood type but there are three possible gene alleles (A, B, and O). Each person has only two of the three specific gene alleles for blood type. One of these alleles is on one chromosome 9 of the pair; the other allele is located on the other number 9 chromosome. Because each person only has two number 9 chromosomes, he or she can have only two alleles for blood type. One gene allele was inherited from the person’s mother, and the other gene allele was inherited from the person’s father. Some traits have even more than three possible alleles, but each person has only two. Which blood type gene alleles are inherited from a person’s parents determines which blood type he or she expresses.

If a person has inherited a blood type A allele from his or her mother and a blood type B allele from his or her father, he or she has the A and B alleles; the blood type expressed when the blood bank determines type is type AB. Fig. 6-8 shows this concept. In Fig. 6-8, two people are about to become pregnant. What are the possibilities for this baby to have a specific type of ear shape (pointy, rounded, square, triangular)? The gene for ear shape is trait 1, and it (for the purposes of this explanation) is on chromosome number 6.