Anthony B. Wight
The genome is the total genetic material (DNA) present in a single cell nucleus. Each of an adult human’s 10 trillion cells, except for reproductive cells (gametes) and red blood cells, contains essentially the same DNA—3 billion basepairs (bp) divided into 23 pairs of physically distinct units called “chromosomes.”
Each chromosome has a single compressed DNA molecule whose bases average 150 million that would be 2 inches long if released from the cells and stretched out. DNA molecules are the largest known molecules.
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If all of the DNA in one person’s cells were stretched out, it would reach to the moon and back!
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Chromosomes are visible under the light microscope and a set of slides is available in the Teachers’ Institute Library for class use. (Magnification of 400x works well.) Stains reveal a pattern of bands on the chromosomes that reflect variations in the amount of A,T,C,G bases in regions. Differences in size and banding allow each of the 23 chromosomes to be identified and in some cases abnormalities can be spotted by eye that indicate differences in the genomes. Most DNA details, however, can only be detected by molecular techniques. Abnormal DNA may be responsible for inherited diseases or cancer.
Genes are segments of DNA (sequences of bases) which directly convey genetic information as well as the information used by cells to regulate the kind and amount of protein they make. The human genome (3 billion bp) has 50,000 to 100,000 genes. Typically, a gene may contain up to 30,00 bp, but only 10 percent of these pairs are known to contain useful information (exons), while the rest are considered to be stuffer or “junk” (introns). There are about 3,000 to 4,000 genes per chromosome.
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A government sponsored, 15-year human genome project is underway to decipher the complete code of the 50,000 to 100,000 genes—essentially to determine the exact order of the base pair sequences. To accomplish this, the genome must be broken down into genes or other fragments small enough to be clones and then identified. Next, the fragments will be arranged or “mapped” in their respective locations on the chromosomes. Finally, automated techniques will be employed to determine the base sequence of the ordered fragments. The ultimate map will be the base pair sequence for the entire human genome—a “snapshot,” if you will, of the genetic code for the “standard” human being at that moment in time.
As researching this area continues, specific human genes are being identified and mapped or located on specific chromosomes. In 1958 only a handful of gene loci were known; by 1987 nearly 4300 genes were located.
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As any reader of newspapers can tell, new genes are being located nearly daily.
An illustrated lecture is outlined in the lesson plans to assist students in grasping the scale of the genome project. If the number of base pairs of DNA in human cells is considered roughly comparable to the number of people on earth, then mapping the entire sequence of base pairs in one cell is a task comparable to identifying every single person on earth by name and location!
When the human genome map is complete, will it match any individual exactly? No, there is simply far too much variation among specific individuals to expect 3 billion base pairs to line up exactly with the standard sequence. Since all healthy humans have essentially the same genes (only identical twins have exactly the same genotype), the map will provide an exceptionally accurate diagnostic tool.
How Does the Human Genome Compare With Other Genomes?
Before much was known about the DNA sequences of genomes, it was assumed that the amount of DNA would increase in proportion to the biological complexity of the organism. Since chromosomes can vary in size, the total amount of DNA is a better indication of genome size than the number of chromosomes. Higher plants and animals do have much more DNA than lower organisms. There are, however, interesting exceptions, such as the salamander which has DNA content more than 30 times greater than that of humans, even though it is a smaller, less complex organism. Even the cells of some species of plants have more DNA than human cells as shown in the table below:
(Haploid) Amounts of DNA in Various Organisms28
Organism
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Millions of Base Pairs
|
Bacterium
|
4.7
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Yeast
|
15
|
Nematode
|
80
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Fruit Fly
|
155
|
Chicken
|
1,000
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Human
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2,800
|
Mouse
|
3,000
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Corn
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15,000
|
Salamander
|
90,000
|
Lily
|
90,000
|
Mapping of human and other species’ genomes will enable comparative studies to be done to determine genomic sequences or genes which are conserved among widely varied species. Even without full knowledge of the genomes, it is possible to do comparative evolutionary studies by matching a known sequence probe to the DNA of various species using well established gel electrophoresis and hybridization techniques. The results will show degrees of relatedness or divergence among species with dramatic implications for the construction of evolutionary trees.
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Within any single species, hereditary variation is the result of changes occurring by mutation—changes in the sequence or number of nucleotides—which occurs during DNA replication. Mutations formed in sex cells are inherited by offspring, whereas those that occur in other cells remain only in the affected organism. Some diseases, such as human cancers, can be caused by factors in both of these categories. Mutations can also be the result of artificial causes, such as exposure to radiation or certain chemicals. A change in even just a single base pair may modify or shut down a protein, if one is encoded in the altered region of the chromosome. More extreme mutations, involving changes in structure of a chromosome or number of chromosomes can also occur.
In diploid cells, each DNA molecule has a tendency to undergo some modification or rearrangement with each cell division.
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In meiosis, two rounds of cell duplication occur, resulting in four daughter cells, each with a haploid set of chromosomes. Before the first division, each member of a chromosome pair is replicated, forming two sets of chromosome pairs. At this stage, the cell has two identical copies of maternal origin chromosomes, and two identical copies of paternal origin. An event called “crossing over” or “recombination” can occur in which one maternal and one paternal chromosome exchange corresponding sections of DNA. In this way, two of the four resulting sex cells have chromosomes with new combinations of genes and thus new combinations of traits are created.