The human genome is the whole of the heritable genetic material that directs the development of the human organism. Authors of popular works on science usually liken the genome to a "blueprint" that directs the construction of our physical being. But, personally, I find more congenial and understandable the description of the genome as a book—written in a particular language, subdivided into sections, chapters, paragraphs, sentences, words, each composed by multiple letters–all of which mean something and transmit this meaning to the reader.
This "book" has 23 chapters (chromosomes), and each chapter contains several thousand stories (genes). Each story is made up of paragraphs (exons), which are interrupted by "advertisements" (introns). Each paragraph is in turn made up of words (codons).There are one billion words in the book. Each of the three-letter words is written using only four letters (bases): A, C, G, and T, which stand for Adenine, Cytosine, Guanine, and Thymine: Simple, isn't it? No? Well, let us see.
Every man starts life as just a single cell, formed by the fusion of his parents' germ-cells (ovum, i.e., the unfertilized egg, and sperm). All the information needed to build up the adult body is contained inside that initial cell, in its nucleus, where there are thousands of genes2 on 23 pairs of threadlike bodies called chromosomes.
Differences among individuals conceived from the same parents arise from the particularities of the process of reproduction. The two gametes (the germ-cells; that is, sperm and ovum) are produced in the gonads (ovaries in females and testes in males), by a process called meiosis. Because of the assortment and separation of chromosomes during this process, each one of us produces gametes containing diverse combinations of the chromosomes we inherited from our parents. During meiosis, another process, called recombination, or "crossing over," produces individual chromosomes that combine genes inherited from the two parents. A human ovum, representing one of approximately 8 million possible chromosome combinations, will be fertilized by a single sperm cell, which represents one of 8 million different possibilities. In this manner, it results that a child's chromosome set is unique to him.3
When the child is conceived, the fusion of the gametes gives him a complete set of 46 chromosomes (one set of 23 from the father's sperm and the other 23 from the mother's ovum). The two chromosomes of each pair carry genes controlling the same inherited trait (for example, if a gene of eye color is situated in a particular place in a chromosome, its homologue will also have a gene specifying eye color in that place).4 If the two genes are identical, the person will show the trait that they specify; say, blue eyes. However, if the genes are different,5 one will be dominant and the other recessive—that is, the dominant will express the trait it commands, overriding the trait expressed by its pair, and the recessive will remain hidden in the background, not expressed.
Every one of the 100 trillion cells that compose the human body contains an exact copy of the individual's unique sequence of genes in 23 pairs of chromosomes put together at the moment of conception.
THE "LANGUAGE" OF GENES
But what is a "gene"? A gene is, in simple words, a set of instructions that tells a cell exactly how to make a certain kind of protein. Every human body is built and run with fewer than 100,000 kinds of protein molecules.
Virtually every process and product in living cells depends on proteins. They do everything from activating essential chemical reactions, to carrying messages between cells, to fighting infections, to making cell membranes, tendons, muscles, blood, bone, and other structural materials....Despite their many different functions, all protein molecules are constructed in the same basic way. They are long, folded chains of smaller molecules called amino acids.
Each "word" in the sequence tells the cell what raw materials to take and the order in which to produce the different amino acids which, in turn, make up the proteins. There are 20 different kinds of amino acids,8 the same in all living organisms, from protozoa to plants, animals and humans. Most of the common proteins are formed by more than 100 amino acids. "The numbers, types, and arrangement of amino acids in a protein molecule determine its structure, and its structure determines the job it will do in a living organism. The shape of some proteins is very sensitive to the arrangement of particular amino acids, and a change in the identity of only one amino acid can cause very subtle, or very profound, effects—like a misspelled word altering the meaning of a sentence."9
THE DOUBLE HELIX
Each chromosome is one pair of long DNA (deoxyribonucleic acid) molecules, built up by nucleotides, repeating subunits of three linked molecules—base, sugar and phosphate.
The usual state of DNA is a "double helix," the original strand and a complementary pair intertwined, like a twisted rope ladder (the side "ropes" of sugar and phosphate) with wooden rungs (the complementarily bonded pairs of bases).10
The bases are complementary, that is, A on one chain bonds only to T on the other (thus forming an A-T ladder rung); similarly, C on one chain bonds only to G on the other. If the bonds between the bases are broken, the two chains unwind, and free nucleotides within the cell attach themselves to the exposed bases of the now-separated chains. These free nucleotides line up along each chain according to the base-pairing rule (A bonds to T, C bonds to G). This process results in the creation of two identical DNA molecules from one original and is the method by which hereditary information is passed from one generation of cells to the next.
The human genome is composed of about 3 billion base pairs and possibly contains 50,000 genes. The genes take up only about 5 to 10 percent of the DNA; some of the remaining DNA, which does not code for proteins, may regulate whether or not proteins are made, but the function of most of it is still uncertain.
What is known is that the DNA sequence also includes groups of genes (regulator genes) that promote or inhibit the activity of the other, protein-producing genes (structural genes). There is also a third type of genes (operator genes), which control the activity of either one or multiple regulator genes, together with their structural genes. When genetic engineers transfer genes from one organism to another, they must include all these "switches" that control the genes, as well as the genes themselves.
THE DNA DOUBLE HELIX
The DNA molecule is a double helix composed of two strands. The sugar-phosphate backbones twist around the outside, with the paired bases on the inside serving to hold the chains together. Adenine (A) pairs with Thymine (T); Guanine (G) pairs with Cystosine (C).
All the cells in a human body contain identical copies of the genome (the complete sequence of genes, but only relatively few (1,000-5,000) are at work— "expressed"—in every cell at any one time. The others are inactive ("repressed" or "turned off") much or even all of the time.
Most of the active structural genes perform "housekeeping" chores, carrying out the metabolic reactions common to all cells, but a few (100) carry codes for proteins needed only in that type of cell. For example, while all the cells of the body have the genetic information to make insulin,11 this protein is manufactured only in the pancreas, to be carried by the bloodstream to all the other cells where it is needed.
As we have seen, genetic variation among individuals conceived by the same parents is primarily accounted for by the process of reproduction.
A further source of genetic variation in the individual arises from the process of mitosis, the reproduction of the body's cells. The DNA content of each cell must accurately replicate itself before division to be passed on to the newly formed cell. Given the complexity of the DNA molecule and the vast number of cell divisions that take place within the lifetime of an organism, it is obvious that "copying" errors are likely to occur. Drastic changes—provoked by radiation, chemicals, etc.—in the physical environment with which the genes interact may also provoke replication errors. Such errors change the linear order of the DNA bases and produce mutations in the genetic code.12
The two usual sources of genetic variation are chromosomal mutations and gene mutations. Chromosomal mutations include duplication, deletion, or rearrangement of chromosome segments. Gene mutations result from a change in the stored chemical information in DNA. Such a change may include substitution, duplication, or deletion of nucleotides. The substitution of one nucleotide base for another may result in the incorporation of one wrong amino acid into the chain encoded by the gene, which affects the functioning of the protein to be made. In many cases, the effects are minor, but there are exceptions: the human disease sickle-cell anemia, for example, is the product of a single base substitution inherited from both parents. Although we talk as if a particular "gene" directly determined a specific trait, the "genetic difference" is due, not to the presence of something, but to the absence of the ability to make a specific protein, to which the organism reacts.13
To simplify, we have followed a textbook explanation and reduced the "gene" to little more than a protein-coding molecular sequence. It is misleading. Genes can manifest a position effect, changing if they move on to another place in the chromosome; organisms that possess mostly the same proteins and associated regulators can vary dramatically, and if genes simply code for proteins, it means that they only specify cellular composition—then, where does the complex structure of the organs come from?14
Much is still unknown, but it is certain that the great majority of human traits involve complex interactions of genes, biochemistry, environment, society, and free will.15 The genes, by themselves, are not determinative of the whole that is the human being. —Fr. Juan Carlos Iscara
2. For the time being, nobody knows with certitude how many genes are in the human genome. Habitual estimates ranged from 80,000 to 140,000. Scientists at Celera Genomics, the laboratory most advanced in the decoding of the genome, consider now that there are only about 35,000 to 50,000 genes in the genome's 3 billion base pairs.
3. See Campbell, Biology, 245-256.
4. Campbell, Biology, 246.
6. Except the germ-cells, which have only 23 chromosomes, and the red blood cells, which have none.
7. Grace, Biotechnology, 21-22.
8. Ten of these amino acids are supplied to the organism in our food, but the other ten have to be synthesized by our body. To let you recognize them the next time you read the nutritional information on your cereals box, the names of the 20 amino acids are: arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine.
9. Grace, Biotechnology, 23.
11. A protein composed by more than 50 amino acids; required for the processing of sugars.
12. Encyclopedia Britanica, "Heredity."
13. Moss, Gene, 46-47.
14. Penman, What Are Genes? 66.
15. Hayes, Human, 87,