We are eukaryotes, organisms with cells having a true nucleus bounded by a nuclear membrane, with multiplication by mitosis. Bacteria are prokaryotes, organisms without a true nucleus, with reproduction by cell division. With the exception of DNA within mitochondria, all of our DNA is packaged in a nucleus surrounded by a nuclear membrane. Mitochondria are believed to be descendants of primitive bacteria engulfed by our ancestors, and they still contain some important genes. Because ova are rich in mitochondria, diseases due to mitochondrial genes (for example, Leber’s optic neuropathy) are transmitted by the mother. The mitochondria in sperm are eliminated during fertilization.

Chromosomes are packages of genetic material, consisting of a DNA molecule (which contains many genes) to which are attached large numbers of proteins that maintain chromosome structure and play a role in gene expression. Human somatic cells contain 46 chromosomes, 22 pairs of autosomes, and one pair of sex chromosomes. All somatic cells are diploid—23 pairs of chromosomes. Only gametes are haploid, with 22 autosome chromosomes and one sex chromosome. The chromosomes vary in size, ranging from 50 million to 250 million base pairs. Chromosome 1 contains the most genes (2,968), and the Y chromosome has the smallest number (231). All contain a pinched portion called a centromere, which divides the chromosome into two arms, the shorter p arm and the longer q arm. The two members of any pair of autosomes are homologous, one homologue derived from each parent. The number of chromosomes does not indicate the level of evolutionary sophistication and complexity; the dog has 78 chromosomes and the carp has 104!

A single gene is a unit of DNA within a chromosome that can be activated to transcribe a specific RNA. The location of a gene on a particular chromosome is designated its locus. Because there are 22 pairs of autosomes, most genes exist in pairs. The pairs are homozygous when similar and heterozygous when dissimilar. Only 2% of the human genome
consists of genes that encode protein synthesis. In 1952, Alfred Hershey and Martha Chase confirmed that DNA is the source of genetic transmission. Their report is famously known as the blender experiment, in which labeled DNA in bacteriophages infected bacteria and blender agitation separated the phage particles, demonstrating that the radioactive tracer was present only in the bacterial cells.

The usual human karyotype is an arrangement of the chromosomes into pairs, usually after proteolytic treatment and Giemsa staining to produce characteristic banding patterns, allowing a blueprint useful for location. The staining characteristics divide each arm into regions, and each region into bands that are numbered from the centromere outward. A given point on a chromosome is designated by the following order: chromosome number, arm symbol (p for short arm, q for long arm), region number, and band number. For example, 7q31.1 is the location for the cystic fibrosis gene.

DNA is the material of the gene responsible for coding the genetic message as transmitted through specific proteins. Thus, it is the most important molecule of life and the fundamental mechanism for evolution. Genes are segments of DNA that code for specific proteins, together with flanking and intervening sequences that serve controlling and regulating functions. Each molecule of DNA has a deoxyribose backbone, identical repeating groups of deoxyribose sugar linked through phosphodiester bonds. Each deoxyribose is attached in order (giving individuality and specificity) to one of four nucleic acids, the nuclear bases:

A purine—adenine or guanine.

A pyrimidine—thymine or cytosine.

A nucleotide is the basic building block of DNA. It consists of three major components: the deoxyribose sugar, a phosphate group, and a nucleic acid base. The phosphate-sugar
linkages are asymmetric; the phosphorus is linked to the 5-carbon of one sugar and to the 3-carbon of the following sugar. Thus, one end is the 5′ (5 prime) end and the other the 3′ (3 prime) end. By convention, DNA and its nuclear acid sequences are written from left to right, from the 5′ end to the 3′ end, the direction of the transcription process. The 5′ end leads to the formation of the amino end of the protein; the 3′ end forms the carboxy end of the protein.

DNA consists of two deoxyribose strands twisted around each other clockwise in a double helix, with the nucleic acids on the inside and the nuclear bases paired by hydrogen bonding, adenine with thymine and cytosine with guanine. RNA differs from DNA in that it is single stranded, its sugar moiety is ribose, and it substitutes uracil for thymine. Phoebus Levene, a Russian immigrant to the United States, working at the Rockefeller Institute of Medical Research from 1905 until he died in 1940, identified the components of DNA (discovering and naming the ribose and deoxyribose sugars) and was the first to suggest the nucleotide structure, research that provided the foundation for the later delineation of the DNA’s significance.

How can a cell’s DNA, which stretched out measures nearly 2m long, fit into a cell? Watson and Crick figured this out when they proposed a tightly coiled two-stranded helix, the double helix. Like the centimeter is a measure of length, the base pair (bp) is the unit of measure for DNA. The base pair is either adenine-guanine or cytosine-thymine, the nucleic acid of one chain paired with the facing nucleic acid of the other chain. A fragment of DNA, therefore, is measured by the number of base pairs, e.g., a 4,800-bp fragment (a 4.8 kb fragment). It is estimated that we have nearly 3 billion bp of DNA, only a small portion of which actually codes out for proteins.

DNA does not exist within the cell as a naked molecule. The nucleotide chains wind about a core of proteins (histones) to form a nucleosome. The nucleosomes become condensed into many bands, the bands that are recognized in karyotype preparations. This condensation is another important mechanism for packing the long DNA structure into a cell. Many other proteins are associated with DNA, important for both structure and function.

The process of DNA replication begins with a separation of the double-stranded DNA helix, initiated at multiple steps by enzyme action. As the original DNA unwinds into template strands, DNA polymerase catalyzes the synthesis of new duplicate strands, which re-form a double helix with each of the original strands (this is called replication). Each daughter molecule, therefore, contains one of the parental strands. It is estimated that the original DNA molecule present in the fertilized zygote must be copied approximately 1015 times during the course of a human lifetime. Rapidity and accuracy are essential. By combining precision with error correction systems, errors that affect the function of the gene’s protein are surprisingly rare.

The homeobox is a DNA sequence, highly conserved throughout evolution, that encodes a series of 60 amino acids, called a homeodomain. Homeodomain protein products function as transcription factors by binding to DNA. The homeobox influences specific tissue functions that are critical for growth and development of the embryo.