Genetics

At its most basic, genetics is the study of genes, which are sequences of DNA (deoxyribonucleic acid) that instruct cells to function through chemical processes, especially the production of proteins. Genes are passed from parents to their offspring, making them the basic units of heredity, or the passage of traits from generation to generation. Heredity and genetic variation are seen as key drivers of evolution by natural selection, making genetics an important subject in virtually every field of biology. Some of the key subfields of genetics include population genetics, medical genetics, and epigenetics. Another closely related science is genomics, which focuses on complete sets of genes in organisms—genomes—rather than individual genes.

Early Developments

While the science of genetics only developed beginning in the late nineteenth century, humans have witnessed and manipulated heredity for much longer. Before any recorded history, ancient humans chose alert pups from a litter of wolves for breeding. This practice of selectively breeding the wolves that were good companions eventually gave rise to the domesticated dog. Some of the oldest undisputed dog bones known, excavated from a twenty-thousand-year-old Alaskan settlement, demonstrate that prehistoric humans knew that traits could be passed from one generation to the next, and that selectively breeding animals (or plants) could produce an organism that possessed desired characteristics. This practice of deliberate breeding is known as artificial selection.

Humans have practiced artificial selection on numerous animals, including pigs, cattle, goats, and sheep. Homer and other Greek poets wrote about selective breeding, and part of the wealth of the ancient city of Troy was attributed to its expertise in horse breeding. Although humans had some control over the traits of domesticated animals through selective breeding, the results of matings were not always predictable, and nothing was known about the mechanism through which traits were passed from one generation to another until the mid-1800s.

Mendelian Genetics

Gregor Mendel, an Austrian monk, is the undisputed father of the science of genetics. Working with garden peas, Mendel analyzed thousands of breeding experiments to describe laws that governed the inheritance of traits. Though Mendel studied a plant, Mendel's Laws of Heredity apply to all sexually reproducing organisms, including humans.

Mendel chose seven distinct traits to study in his garden peas: flower color, plant height, seed shape, seed color, pod shape, pod color, and flower position. He concluded that each of these traits was determined by a single, discrete factor, later to be called a gene. For instance, there was a gene for flower color and a gene for seed shape. Each gene had several variations, or alleles. The gene for flower color had a white allele that produced white flowers and a purple allele that produced purple flowers.

Mendel’s experiments revealed that organisms have two copies of any gene for a trait. Those two copies can be identical, two purple alleles of the flower color gene, or those two alleles can be different. A pea plant could have one purple allele of the flower color gene and one white allele of the flower color gene. When an organism has two identical alleles of a gene, it is homozygous for that gene. When an organism has two different alleles of a gene, it is heterozygous for that gene.

An organism inherits one allele, or copy of a gene, from one parent and one allele from the other parent. An organism, or cell, that has two copies of all of its genetic information is called diploid. In most sexually reproducing animals, the offspring are formed when a sperm cell from the male parent fertilizes an egg from the female parent. The sperm and the egg only contain half of all the genetic information. They are said to be haploid. However, the new organism they create is diploid because it gets one copy of the genetic information from the sperm and a second copy from the egg.

Mendel’s first law, or the law of segregation, states that the two copies of each gene separate during the formation of gametes (eggs and sperm), and that fertilization of the egg by the sperm is a random event. Any sperm containing any allele of a gene can fertilize any egg of the same species, regardless of the allele carried by that egg.

Mendel noted that certain alleles seemed to dominate over others. For instance, when a plant had a purple allele for flower color and a white allele for flower color, the plant always had purple flowers. Mendel called the allele that was seen in the heterozygote, in this case, the purple allele, the dominant allele. The allele that was hidden or masked, he called the recessive allele. To show a recessive allele, an organism has to have two identical copies of a gene, both containing the same recessive allele. This is known as the homozygous recessive condition. Garden peas that have white flowers are homozygous recessive for the white allele of the flower color gene.

Homozygous recessive describes the organism’s genotype, or its genetic makeup. It has two copies of the recessive allele of the gene. The observable characteristic of the organism, having white flowers, is called its phenotype.

Mendel also demonstrated that the segregation of alleles of any one gene is not dependent on the segregation of alleles of any other gene. For instance, a gamete could receive a dominant allele for an eye color gene and a recessive allele for height, or that gamete could receive the recessive alleles for both genes or the dominant alleles of both genes. This is Mendel’s second law, the law of independent assortment, and it applies to any genes that are located on separate chromosomes.

Mendel’s work was far ahead of its time. Although Mendel published his research in the 1800s, it was not until after his death that his work gained recognition in the scientific community. In 1900, three other scientists, each working separately on inheritance, came across Mendel’s work in the course of their research. They gave him credit for his insights, and Mendel’s research provided the foundation for the new discipline of genetics. An entire branch of the science is still known as Mendelian genetics.

Genes and Chromosomes

Although Mendel described the gene as the factor that was responsible for a particular trait, nothing was known about the physical makeup of a gene. (The term "gene" itself, as well as "genotype" and "phenotype" would be coined by Danish scientist Wilhelm Ludvig Johannsen in 1909.) One of the first questions scientists needed to answer was where genes are found in cells. Early studies in frogs and sea urchins indicated that the nucleus of the sperm and the nucleus of the egg combined with each other during fertilization. This observation suggested that the genetic material that determined how the fertilized egg would develop might reside in the nucleus.

As microscopes improved, scientists were able to distinguish structures within the nuclei of cells. These long, threadlike structures stained blue and were called chromosomes (Greek chroma, "color"). Several scientists observed that when animal and plant cells divided, the chromosomes duplicated, then separated, and each daughter cell inherited a complete set of chromosomes. The one exception to this was the cell division that produces the gametes (eggs and sperm). When an egg or a sperm cell was produced, it only contained half the number of chromosomes as the cell that produced it. If genetic information was carried on chromosomes, scientists reasoned that a sperm and an egg could each contribute half of the genetic information to the new organism at fertilization.

Some of the first evidence that chromosomes were linked to observable traits came from the studies of American graduate student Walter S. Sutton. Sutton studied grasshoppers, and his observations of chromosomes indicated that male grasshoppers always had an X and a Y chromosome, whereas female grasshoppers contained two X chromosomes. Several other scientists observed similar things in other organisms, such as fruit flies, and concluded that the physical characteristic of sex was determined by the kind of chromosomes an organism possessed.

Since chromosomes determined the trait of sex, it was possible that chromosomes contained the genes that Mendel had shown to determine physical characteristics. The first scientist to demonstrate that genes were located on chromosomes was Thomas Hunt Morgan, who showed that an eye-color gene in the fruit fly, Drosophila melanogaster, was located on the X chromosome.

Next, scientists wanted to know what kind of chemical molecule carried the genetic information. Chromosomes contain two kinds of molecules, protein and a weak acid called deoxyribonucleic acid (DNA). Experiments in the early 1930s first demonstrated that DNA is the genetic material. Oswald Avery, Colin MacLeod, and Maclyn McCarty showed that adding DNA to these bacterial cells could change their physical traits. In their experiments, they mixed a harmless strain of bacteria with DNA from bacteria that caused disease in mice. When they did this, the previously harmless bacteria changed (or transformed) into disease-causing bacteria. Two other scientists, Alfred Hershey and Martha Chase, later obtained similar results by studying a virus that infects E. coli.

Molecular Genetics

By the 1940s, scientists knew that genetic information was carried by genes made of DNA molecules inside cell nuclei. However, scientists did not know how the genetic information was copied accurately from one generation to the next—from one cell division to the next. Nor did scientists know how the DNA could account for the appearance of inherited changes or mutations. To answer these questions, scientists needed to know the precise chemical structure of DNA.

Many scientists contributed to the understanding of the structure of DNA. Erwin Chargaff obtained data that indicated that specific molecular components of the DNA molecule were always present in equal parts. These components were nitrogen-containing molecules (or nitrogenous bases). Chargaff determined that the nitrogen-containing bases adenine and thymine were always present in a one-to-one ratio, and the bases guanine and cytosine were always present in a one-to-one ratio, no matter what species’ DNA was analyzed.

Simultaneously, two scientists at Kings College in London, Rosalind Franklin and Maurice Wilkins, were attempting to make X-ray pictures of DNA molecules. Franklin obtained an X-ray film that indicated that DNA was a helical molecule. Just before Franklin’s work, an American chemist, Linus Pauling, had made a breakthrough in solving the structure of the protein alpha helix using a model-building approach.

Two scientists working at Cambridge University in England, James D. Watson and Francis Crick, decided to use Pauling’s method of model building to attempt to solve the structure of the DNA molecule. Combining the data from a variety of sources, including the work of Chargaff and Wilkins, and the crucial X-ray crystallography data of Rosalind Franklin, Watson and Crick solved the structure of the DNA molecule.

Watson and Crick created a model of DNA: a double helix, like a twisted ladder. The DNA molecule was a long polymer of repeating nucleotides. Each nucleotide contained three chemical parts: a sugar, a phosphate group, and a nitrogen-containing base. The sides of the double helix ladder were formed by alternating sugars and phosphates, and the rungs were formed on the inside of the helix by specific pairings of the nitrogen-containing bases. Adenine paired with thymine to form one kind of rung. Guanine paired with cytosine to form a second kind of rung.

The order of the bases provided the information within DNA. Certain combinations of bases could form "words" that stood for parts of proteins or other molecules encoded by the DNA. The double helix could unzip like a zipper, each strand serving as a template to guide the construction of a new strand. This provided an accurate means for copying the DNA molecules from a parent cell to a daughter cell.

Genetic Engineering

The details of how DNA is passed from one generation to the next, of how mutations arise, and of how the information of DNA is translated into the activities of cells form the basis of genetic research at the beginning of the twenty-first century.

One of the most important scientific discoveries that led to modern genetic technology was the discovery of a particular kind of protein, a restriction enzyme, from bacteria that cuts DNA molecules at specific sequences of bases. These restriction enzymes gave scientists the tool they needed to break DNA down into smaller pieces, eventually allowing the isolation of individual genes from the huge amount of DNA inside the nucleus of the cell.

Herbert Boyer and Stanley Cohen combined their knowledge of restriction enzymes and bacterial transformation (getting bacteria to take up DNA from the environment) to develop recombinant DNA technology and clone genes. Gene cloning involves isolating a gene of interest by using a restriction enzyme to cut it away from other DNA and placing it in a piece of DNA called a vector that can be taken up by bacterial cells. One of the first applications of this technology was the production of human insulin. Scientists isolated the gene that encodes the information for making insulin from human DNA, cloned it into a bacterial vector, and placed the vector with the insulin gene in E. coli. The E. coli cells were able to produce large quantities of insulin. This new insulin was considerably cheaper and safer than insulin purified from human tissue.

Variations on this technique of taking a piece of DNA from one species and inserting it into the cells of another species are involved in genetic engineering of multicellular organisms. In multicellular organisms such as plants or monkeys, the DNA vector is usually a modified virus. These techniques are the basis of human gene therapy.

In the last decade of the twentieth century, entire organisms were cloned. In Scotland, Ian Wilmut and colleagues reported the first mammalian cloning of a sheep named Dolly. In Wisconsin and Japan, scientists have cloned cattle. When an organism is cloned, all its DNA, usually contained within an intact nucleus from a cell of the adult animal, is transferred to an egg cell from which all the genetic information has been removed. The egg is then allowed to develop into a new organism. Although the new organism is young, it has the same DNA as the parent from which the nucleus was obtained.

Scientists have also developed techniques for sequencing DNA, determining the exact order and number of nitrogenous bases within the DNA of an organism’s genome. In 2003, the Human Genome Project announced that the entire genome of the human had been sequenced. Many other genomes have been sequenced, including the roundworm, C. elegans, several plants, and even baker’s yeast. The sequence of an organism gives scientists another tool in answering questions about how DNA regulates and determines the activities of cells. Other genome mapping projects include the 1000 Genomes Project, which concluded in 2015, and the telomere-to-telomere (T2T) consortium, which generated the first gapless human genome sequence in 2022.

In the early twenty-first century, applied genetics had become integral in many aspects of society. For example, DNA forensic evidence is now used to convict or exonerate criminal suspects on a routine basis. The genetic engineering of food crops that are pest resistant or contain additional nutrients—known as genetically modified organisms, or GMOs—is also routine. Parents can have an embryo genetically screened for devastating genetic diseases before it is born, while those already born can undergo genetic testing for various conditions. With the cloning of entire organisms made possible, the potential cloning of a human has moved beyond the realm of science fiction. While many of these advances are clearly positive, many of them are double-edged swords, begging for informed public debate.

To many, the ethical consequences and risks of genetic engineering remain the subject of intense controversy. Some people reject human interference in natural processes on religious grounds, while others suggest that genetically modified foods may be unhealthy or have negative effects on the environment. Proponents of genetic engineering counter that humans have been manipulating genes for thousands of years—domesticated crops and animals are all technically "genetically modified"—and argue that genetics holds the potential to improve and save countless lives. Other critics do not necessarily object to genetic engineering itself but note that the practice raises major ethical issues of accessibility and equality. They warn that the expense of genetic research and engineering threatens to give the already wealthy and powerful exclusive access to beneficial treatments and technology, while genetic testing and genetically altered designer babies could eventually lead to discrimination.

Principal Terms

Allele: Alternative forms of a single gene

Chromosome: A long strand of DNA with supporting proteins, that contains many genes

Deoxyribonucleic Acid (DNA): The chemical polymer that is the genetic material of multicellular organisms

Gene: Factors in cells that are responsible for an observable characteristic of an organism

Genome: All the genetic material of an organism

Genotype: The actual genetic makeup of an organism

Mutation: Any heritable change in the genetic material

Phenotype: The observable characteristics of an organism (for example, black fur color in a cat)

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