3.4Differences between Individuals and Species


Individual Differences and Genomes

After reading the whole genome of humans, researchers turned their attention to the diversity of human organisms at the genomic level. Humans produce gametes by meiosis, during which genetic recombination occurs. In addition, DNA is sometimes damaged by ultraviolet radiation and oxidative stress, causing a mutation in the base sequences. If such a mutation occurs in a germ cell, it will be transmitted to subsequent generations. This kind of genetic mutation and recombination is repeated in the genomic sequence. Thus, the genomic sequence is unique and varies slightly from person to person.
Single Nucleotide Polymorphisms (SNPs*14 ) are common in the human genome. Nearly 10 million SNPs have been submitted to databases. Simple calculations show that 1 in 300 bases has an SNP.
Both genetic factors and environmental factors must be considered as factors in human development. Regarding genetic factors, individual differences are expressed as phenotypes by the accumulation of mutations and polymorphisms such as SNPs.

*14 Pronounced "snip"


The Right to Know and to Not Know

Now that the human genome project has been completed, the responsible genes for many genetic diseases are being discovered at the DNA level. Today, it is easy to find out whether a mutation that causes a genetic disease is present in a person's DNA just by taking DNA from a person and analyzing its sequences.
This situation can be considered an example of scientific progress, but is this always a good thing? How would you feel if you analyzed your own DNA sequences and found a disease-causing genetic mutation?
Such situations pose the problem that knowing genetic information is not in itself an advantage. Presently, the "right to know" and the "right not to know" the results of genetic diagnoses are both accepted.

Column Fig. 3-1. Genetic Mutations and Family Lineage

In this family tree, the circles are females and the squares are males. The black symbols represent carriers of the disease-causing genetic mutation "A." The numerals indicate age. The diagonal lines represent members who have already died. This genetic disease is transmitted as a dominant trait. The question is whether the mother in this family tree (indicated in red) may or may not carry the genetic mutation.

However, the "right to know" and the "right not to know" involve much more difficult problems than expected. Consider the following example.
A woman visited a doctor and told him, "My mother passed away because of a genetic disease. Now that the human genome project has been completed, the responsible gene for the genetic disease has been identified. This disease generally occurs in 1 in 100,000 people, but since it is a dominant trait, a person who has a parent with this disease has a 50:50 chance of developing it.
Now I have reached the same age at which my mother developed the disease, and I'm very worried that I might develop it too. Family and friends keep telling me that I should have genetic testing done. But if the same mutation that caused my mother's disease is discovered in my DNA, I don't think I'll have the courage or confidence to face that reality. Even from a social perspective, I'm frightened."
In response to this request, the doctor said "Your right not to know has now been established. You don't have to be tested" and sent her home.
However, this woman had a daughter, and she wanted to know whether she would develop the same genetic disease that her grandmother had. Given recent progress in modern medical science and technology, she knew an earlier discovery would lead to a better treatment. Since no one in her father's ancestral line had had this genetic disease, the daughter did not have to worry about whether she would develop the disease if her mother did not have the genetic mutation that caused it. Therefore, the child wanted her mother to receive genetic testing, but her mother did not want to be tested.
In exasperation, the daughter brought her own DNA to the hospital without telling her mother and received genetic testing. The results showed that the responsible gene mutation was present in her DNA. Since this genetic mutation was thought to have come from her mother, this also meant that her mother was a carrier of the mutation.
Thus, even when a person opts for the right not to know, her right cannot be protected if other people do not recognize it. We now need to understand that genomic information is not just a matter for the person who is at the risk of developing a genetic disease.

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Species Differences: Differences between Chimpanzees and Humans

Next, let us compare humans with another species—chimpanzees. We can probably think of many differences between chimpanzees and humans, such as the use of complex tools, high-level language, and the so-called cultural life. However, a comparison of genomes in chimpanzees and humans reveals that almost 99% of the DNA sequences of these two organisms are the same, and only 1.23% are different.
On the other hand, if we compare the genomic structure, we can see obvious differences between humans and chimpanzees. The chromosomes that make up the human genome consist of 22 pairs of autosomes and X and/or Y sex chromosomes, but chimpanzees have one additional autosome, making a total of 23 pairs of autosomes and X and/or Y sex chromosomes (Fig. 3-10A). Furthermore, fragments of chimpanzee chromosome numbers 12 and 13 are linked on human chromosome number 2 (Fig. 3-10B). It is thought that large-scale genomic DNA recombination had occurred over the generations in ancestors common to humans and chimpanzees until these two chromosomes fused and became one. Humans are thought to be descendants of a new organism that diverged after such a change in chromosomal structure.
Furthermore, comparisons of proteins expressed in humans and chimpanzees show that many of these proteins contain amino acid substitutions, indicating that there are differences in protein functions between humans and chimpanzees.

Fig. 3-10. A Comparison of Genes in Humans and Chimpanzees

(A) Genome size. Humans and chimpanzees have about the same number of genes, but a different number of chromosomes. Consequently, the two species cannot produce offspring.
(B) Chromosome 2 in humans is formed by a fusion of chimpanzee chromosomes 12 and 13.


Consanguineous Marriage

In humans, the father and mother each transmit one set of chromosomes to their child; consequently, there is a 1/2 probability that a specific gene in the child will come from either parent during gamete formation.
With this fact in mind, let us now make a family tree (Column Fig. 3-2). Grandparents give birth to some children. Suppose that two grandparents have children, who then each get married separately and have children of their own. These children will be each other's cousins. If these cousins marry each other, what will happen if they have children?
As an experiment, let us calculate the probability that two copies of one specific gene on one specific chromosome in the grandmother will be transmitted to a great grandchild whose parents are cousins. Gametes are formed three times—when they are passed from the grandmother to the father, from the father to the grandchild, and from the grandchild to the great grandchild. The probability that one specific gene on one specific chromosome of the grandmother will be passed through her son to her great grandchild is 1/23 = 1/8. Similarly, the probability that the gene will be passed through her daughter to her great grandchild is 1/8. Therefore, the probability that two copies of one specific gene on one specific chromosome are passed from the grandmother to her great grandchild is 1/8 × 1/8 = 1/64.
Since the grandmother and grandfather each have two copies of the chromosome*15, the probability that two copies of the same gene from the same grandparents will be transmitted together to a grandchild whose parents are cousins is generally 1/64 × 4, or 1/16. The number obtained by this calculation is called "inbreeding coefficient," and an inbreeding coefficient of 1/16 is used for marriages between cousins.

Column Fig. 3-2. Family Tree of Marriage between Cousins

Calculation of the probability that a specific gene will be passed on from the grandmother and grandfather to their great grandchild.

If the frequency of expression of a recessive gene that causes a genetic disease is 1/1,000, the probability of becoming homozygous recessive as a result of an arbitrary marriage is 1/1,000 × 1/1,000 = 1/1,000,000. When two cousins marry each other, the probability that their child is homozygous recessive will be approximately equal to the probability 1/1,000 that one of the grandparents has the recessive gene, which is then multiplied by the inbreeding coefficient of 1/16*16. In other words, cousins are 60 to 65 times more likely than the unrelated couples to produce a homozygous recessive child.
The probability of producing a child who is homozygous for a gene steadily increases each time a consanguineous marriage repeats. Japanese law currently allows consanguineous marriage between cousins, which have an inbreeding coefficient of 1/16, but prohibits consanguineous marriage with a higher inbreeding coefficient.

*15 A total of 4 chromosomes
*16 More accurately, 1/16 × 1/1,000 + 15/16 × 1/1,000,000

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Repetition of Replication and Mutation: Diversity and Evolution of Life

Ever since the first primitive life appeared and retained DNA as genetic information, organisms have been continually repeating genetic recombination. This genetic recombination forms new genes. In particular, since sexes became established, genetic diversity has sharply increased through genetic recombination, overlaps, and deletions during the formation of gametes. When there is an exon–intron structure found in eukaryotic cells, and genetic recombination occurs in the intron, a new gene is sometimes formed at the front and rear parts of a gene (see Chapter 4).
The genetic recombination that occurs during the formation of gametes generates diversity in the form of differences between individual organisms. When such diversity exceeds a threshold and an organism loses its ability to breed, a new species will come into existence. This is how diversity as species begins (Fig. 3-11). Humans and chimpanzees probably diverged from a common ancestor while repeating replication and mutation of the genome in this manner.

Fig. 3-11. Schematic Diagram of the Diversity and Evolution of Life

In any given species, there is diversity at the genomic level. If this diversity exceeds a threshold, compatible gametes cannot be passed on, and a new species arises. Diversity once again increases in the new species.

At the same time, this process suggests that even we humans may not continue to exist forever. Replication and mutation are repeated whenever humans leave descendents. Such a process produces diversity in humans, but if this diversity exceeds a certain range, it is possible that a new species of organism will diverge from humans.
The global environment will probably continue to change in future. Even if many species or organisms become extinct, as long as there is diversity of life, some species will adapt to the changes and survive, and diversity will likely increase again.The repetition of replication and matation is the driving force of diversity and evolution of life.


The Genome and Society

Achievements of science and technology in reading genome sequences already benefit us in our lives.
The word "genome" brings to mind diseases and medical treatment. Of course, genomic information can be used in medical treatment to determine the diagnosis of a genetic disease. We may also hear news about genes for longevity, and this is also an example of how genomic information is tied to our lives.
A more familiar example is food testing. It is possible to perform a DNA test on whether beef labeled as a certain brand or as a product of a particular region is actually what it claims to be. What can be covered up by external appearances cannot be done so by DNA sequences.
When a crime has been committed, it is possible to identify the criminal with high certainty by testing DNA on an item that belongs to a suspect. This testing can be performed on minute quantities of cells. Determination of parentage can also be performed according to the same principle.
Such a test mainly uses a laboratory technique called PCR (see Chapter 11). Because of the importance of this technique, the Nobel Prize in Chemistry was awarded to its developer, Kary Banks Mullis, in 1993.
A breed of cattle called Belgium Blue is highly valued for its muscularity and high-quality meat. The high quality of such meat is caused by a mutation in a gene called myostatin. Once genomic sequences are completely known, the use of DNA-sequence information is expected to progress.

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