3.3Reproduction from the Perspective of Genomes


Father and Mother—Various Patterns of Sexes

In animals, the gametes produced in females are called eggs and those produced in males are called sperms. The definition of the word "sex" is based on the existence of males and females.
Various types of marriage have become accepted in human culture, but from a biological perspective, everyone must have one father and one mother. Humans consist of two sexes—male and female—and can produce progeny through reproduction of gametes from both sexes.
This fact seems obvious, but it allows only one possible arrangement of sexes when viewed in context of nature as a whole. Unicellular organisms usually reproduce only by simple cell division. Male honeybees develop from unfertilized eggs, and therefore, have only half the amount of DNA of females. Water fleas (genus Daphnia) go through parthenogenesis*9, which produces only females. In nematodes, sperm-producing and egg-producing organs both exist in the same individual organism, and fertilization occurs within the same organism*10. In water fleas and nematodes, males first appear when the environment deteriorates. Some fishes are known to exhibit dichogamy or sequential hermaphrodism, i.e., sometimes they change from male to female (protandry) and sometimes from female to male (protogyny).
The human genome includes the sex-determining X and Y chromosomes. If the organism receives X chromosomes from both parents and contains the combination XX will be female, and if it contains the combination XY, it will be male. In other words, the biological sex of humans is determined by the combination of chromosomes passed down from the parents. In the above examples of honeybees and fish, sex is determined by the amount of DNA and the environment, respectively.

*9 Reproduction without fertilization.
*10 Called hermaphroditism

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Origin of Sexes

Even in the unicellular organisms mentioned above, cells sometimes fuse, shuffle their chromosomes, and divide back into individual cells. The combinations of the cells that fuse with one another are prescribed by the proteins they express or the kinds of chemical compounds they synthesize; incompatible cells do not fuse. The origin of primitive sexes can be supposed from such phenomena. Furthermore, after the chromosomes of these organisms are shuffled, they exchange their DNA sequences by genetic recombination. This genetic recombination is thought to have an important significance for the existence of sexes.

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Reproductive Cells and Meiosis

Let us take humans as an example: sperm is provided by the father and egg is provided by the mother; when the sperm fertilizes the egg, the development of an individual human begins (see Chapter 5, Fig. 5-1). DNA sequences from both the father and mother are present in the cells of the human body. Therefore, the sperm and egg must each contain half of the parental DNA before fertilization. In fact, germ cells (gametes) with half of the parental DNA are produced by a process called "meiosis" from a primordial germ cell11 that has differentiated specifically for this purpose.
DNA from the father and mother is reshuffled during meiosis. One chromosome comes from the father, another from the mother, and these two chromosomes are randomly redistributed in their offspring. More importantly, even when the two chromosomes are identical, DNA sequences from the father and mother are intermixed by genetic recombination (Fig. 3-8).
In other words, the production of gametes involves genetic recombination and reshuffling of the chromosomes. The sexes of both humans and unicellular organisms are the same in the sense that they both perform the important role of genetic recombination. Furthermore, since genetic recombination disarranges the precise replication of DNA, the existence of sexes and the accompanying genetic recombination create flexibility with respect to changes in genetic information.

Fig. 3-8. Genetic Recombination Occurring during Meiosis

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Artificial Genetic Recombination and Gene Therapy

With the progress in science and technology, it is now possible to manipulate artificial genetic recombination (Fig. 3-9). Furthermore, by effectively utilizing viruses that infect cells, gene therapy is now performed by expressing a normally functioning gene in the body of a patient (see Section 1 of Chapter 11 [11.1.7]).
Today, gene therapy for humans is applied to somatic cells (cells other than germ cells). In other words, gene therapy is performed on the somatic cells of patients to treat diseases.
There is a big difference between gene manipulation in somatic cells and in germ cells. Gene manipulation in somatic cells does not transmit artificial recombinant genes to subsequent generations. In contrast, genetic engineering in germ cells easily reminds us of a superman born with incredible intelligence and legs as fast as bullets (see Column in Section 1 of Chapter 11) *12.
In a scientific sense, genetic recombination that has been established in experimental animals is probably also possible in humans. However, gene manipulation, which introduces recombinant genes into germ cells, has not yet been performed, and the introduction of foreign genes into germ cells is now strictly prohibited*13.

Fig. 3-9. Schematic Diagram of Gene Therapy

Viruses containing artificially constructed DNA are infected into human cells. The infected cell expresses recombinant genes

*11 Cell before it becomes a germ cell
*12 In prenatal genetic testing, genes are taken from a fetus before it is born. Although this process is not gene manipulation, it has already been accomplished (see Section 1 of Chapter 11) .
*13 Even with modern gene therapy, the possibility that an inserted foreign gene enters germ cells cannot be completely disregarded.


Sex Chromosomes and Genetic Diseases

Muscular dystrophy is a disease in which muscles show progressive atrophy and become unable to function in patients. In particular, Duchenne muscular dystrophy, named after its discoverer, is caused by mutations in a gene for a protein called dystrophin.
Duchenne muscular dystrophy is a recessive disorder. In general, if there is even one dominant gene in either of the pair of chromosomes from the father and mother, the phenotype will also be dominant. If both alleles of the gene are recessive, the phenotype will not be expressed. Therefore, one would expect recessive diseases to have lower phenotype expression frequencies than dominant ones. However, Duchenne muscular dystrophy is known to occur at an especially high frequency in males.
This is because the dystrophin gene is on the X chromosome. Females have the XX combination of sex chromosomes; thus, as long as mutations do not occur in both sex chromosomes, muscular dystrophy will not develop. In males, however, the sex chromosome combination is XY. Even though the disease is recessive, its phenotype will be expressed if there is a mutation on just one X chromosome.
As such, the manner in which the phenotypes are transmitted by genes on the sex chromosomes differs between males and females. This mode of inheritance is referred to as "sex-linked inheritance." The Duchenne type of muscular dystrophy mentioned here is an example of a genetic disease that is caused by a sex-linked recessive gene. In contrast, Huntington's disease (see Section 1 of Chapter 11 [11.1.6]) is caused by a mutation of a gene on chromosome 4, and is known to be autosomal dominant.

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