Biochemistry: The Chemical Reactions of Living Cells, Volume 1 - D. Metzler 1980

The Theater of Life
Evolution of Complex Organisms
Mitosis and Meiosis

The Cell Division process known as mitosis initiates and completes the Cell Cycle, during which a single diploid cell divides. From a biochemical standpoint, mitosis involves the duplication of genetic templates followed by The formation of compact structures known as Chromosomes. These chromosomes are distributed equally between two new daughter Cells (this process is described in detail in Chap. 15, Sec. D.9).

What happens to Mitochondria during mitosis? Like METABOLISM/14.html">Chloroplasts in plant cells, they divide. Consequently, at specific Stages of the cell cycle, DNA Replication occurs within these Organelles. In at least some instances, mitochondrial division is so tightly coupled with cell division that the average number of mitochondria per daughter cell remains strictly constant. A similar phenomenon is observed in lower organisms containing symbiotic Algae, even though such algae can live independently outside the host Organism's cells. What compels algae living within host cells to divide synchronously with those cells remains an enigma to biochemists.

¹ The chromosome numbers in some other organisms are as follows: mouse — 20, toad — 11, onion — 8, mosquito — 3, fruit fly Drosophila — 4.

Through successive mitotic divisions, a single fertilized egg develops into an adult organism. For the Formation of the human body, a mere 40–50 consecutive mitoses are sufficient. However, The production of Gametes (Germ Cells), which contain a haploid set of chromosomes, occurs via Meiosis—a specialized process in which the chromosome number is halved. During meiosis, one chromosome from each homologous pair present in the diploid cell is segregated into one of the resulting gametes. In an organism like Ascaris, which possesses a single pair of chromosomes, a gamete receives a chromosome from either the paternal or the maternal organism, but not from both simultaneously. In organisms with multiple pairs of chromosomes, chromosomes assort randomly during meiosis, ensuring that each gamete contains both maternal and paternal chromosomes.

Meiosis is discussed in greater detail in Chap. 15, with particular emphasis on Crossing Over. During this process, which constitutes a crucial feature of meiosis, bonds between genes are broken, thereby enabling the "shuffling" of genes within chromosomes. Crossing over is strikingly similar to genetic recombination in Bacteria and, at THE MOLECULAR LEVEL, is presumably indistinguishable from it.

Box 1-G

Inborn Errors of Metabolism

In 1908, Archibald Garrod (A. Garrod) suggested that cystinuria (Chap. 5, Sec. B.2.b), as well as certain other disorders of Amino Acid and Carbohydrate Metabolism, are Hereditary diseases. Since then, the number of recognized inborn errors of metabolism in humans has been growing at an accelerating pace and currently exceeds 1500^б. For approximately 100 of these, the specific alteration in The Structure of the protein responsible for the metabolic defect has been identified^в-е; Sickle-Cell Anemia serves as a prime example (Box 4-G). In most cases, however, Metabolic Disorders stem from the loss of activity of a required enzyme.

Many Genetic Disorders are quite rare, occurring in no more than 1 out of every 10,000 individuals, whereas others, such as cystic fibrosis, affect 1 in 2,500. The total number of people suffering from hereditary diseases is estimated to exceed 2% of all newborns. Many of these infants perish in early life. An even greater number of people (over 5%) suffer from diabetes and psychiatric disorders, which also have a partial genetic basis. Because The Emergence of new Mutations is a continuous process, genetic diseases present an increasingly urgent problem.

What is the frequency of new mutations? Based on haploid DNA content data (Table 1-3), it can be calculated that the total coding capacity of human cellular DNA exceeds 2 million genes (or more precisely, two million Gene pairs for a diploid cell). However, Proteins are encoded by only a fraction of the DNA. According to various estimates, the number of structural gene pairs in humans ranges from 20,000 to 100,000. Looking to bacteria for a benchmark, we note that the frequency of readily detectable mutations in bacteria is about 10^-6 per gene, or 10^-9 per base pair per division. Consequently, one would expect that upon the replication of 2∙10⁹ Base Pairs (the approximate number contained in Human chromosomes), roughly 2 errors would occur per cell division. Because germ cells undergo several divisions from one human generation to the next, the mutation rate per generation must be quite substantial. Another source of novel mutations is damage to double-stranded DNA that may accumulate over a single generation (approximately 20 years). Without a doubt, the majority of such lesions are repaired by complex repair systems (Chap. 15), but some persist. Fortunately, many mutations prove to be harmless or nearly harmless, and some may even be beneficial. It is also possible that the eukaryotic replication machinery makes fewer errors than that of bacteria. On the other hand, environmental pollution by mutagenic chemicals is a cause for serious concern, as it represents a novel source of mutagenesis.

Many mutations are lethal. A homozygote carrying a lethal mutation fails to survive, resulting in a Spontaneous Abortion (which usually goes unnoticed). Evidence indicates that completely healthy individuals may harbor up to 10 recessive lethal mutations, alongside at least 3–5 autosomal recessive mutations that entail severe genetic defects. Deleterious dominant mutations are also frequently encountered in populations. Specifically, they manifest as elevated Blood lipoprotein levels and increased Cholesterol concentrations, which in turn lead to an increased incidence of cardiovascular disease at a young age.

Biochemical disorders are of immense theoretical significance because they shed light on the roles of individual metabolic pathways; we will frequently discuss such diseases throughout this book. Naturally, the primary objective in studying these conditions is to discover treatments. In certain instances, such as phenylketonuria (Chap. 14, Sec. 3.5) or galactosemia (Chap. 12, Sec. A.1), timely dietary modification can prevent irreversible damage to the Brain—the organ that typically suffers first in these disorders. For many other conditions, effective therapies do not yet exist; the pursuit of Methods to introduce missing Enzymes into the organism—a form of "Gene Surgery"—represents one of the most exciting frontiers in modern medical biochemistry (Chap. 15, Sec. 3.4).

^а Garrod А. Е., Inborn Errors of Metabolism, Oxford, London, 1909.

^б Friedmann T., Roblin R., Science, 175, 949–955 (1972).

^в Stanbury J. B., Wyngaarden J. B., Fredricksen D. S. eds., The Metabolic Basis of Inherited Disease, 3rd ed., McGraw-Hill, New York, 1972.

^г Brock D. J. H., Mayo O., eds., The Biochemical Genetics of Man, Academic Press, New York, 1972.

^д Thompson R. H. S., Wooiion I. D. P., Biochemical Disorders in Human Disease, 3rd ed., Academic Press, New York, 1970.

^e Watson J. D., Molecular Biology of the Gene, 3rd ed., p. 254, Benjamin, Menlo Park, California, 1976.