Genetics

VII

History

Humans have had some understanding of heredity since prehistoric times, observing how similar traits pass from parent to offspring and noting that differences arise with each generation. Most of the mechanisms of heredity, however, were shrouded in mystery until early in the 20th century. Since that time, the rate of discovery has reached a feverish pace, enabling the advancement of modern molecular biology and the current Human Genome Project.

A

Early Views of Heredity

In ancient times, people understood some basic rules of heredity and used this knowledge to breed domestic animals and crops. By about 5000 bc, for example, people in different parts of the world had begun applying selective breeding techniques to grow new plant varieties, including types of wheat, maize, rice, and date palms, that had never existed in the wild.

Ancient people understood that the rules of inheritance also applied to humans. The ancient Greeks were particularly interested in human heredity and evolution. Greek scientists and philosophers hotly debated whether a male or female parent contributed more to an offspring. In the 4th century bc, Aristotle speculated that acquired characteristics, such as a scar that was incurred during life, could be passed on to offspring. He also believed in a widely held theory known as pangenesis. This theory proposed that particles in the body, called gemmules, reside in the limbs and organs. The gemmules become imprinted with any changes acquired by the body, such as muscle development from exercise. The gemmules then move to the reproductive cells and transfer information about the body’s alterations to these cells. The reproductive cells transmit the acquired traits to offspring through particles called pangenes.

The theories about the inheritance of acquired characteristics and pangenesis persisted until the middle of the 19th century. French zoologist Jean-Baptiste Lamarck formalized the theory of acquired characteristics in his treatise Philosophie Zoologique (1809). Lamarck proposed that organisms evolve by responding to changes in their environment. When organisms undergo a change in order to adjust to their environment, that change acts as a trait that can be passed on to offspring.

---

---

B

Influences of Darwin and Mendel

A surprising supporter of pangenesis was the British naturalist Charles Robert Darwin, who believed that the theory accounted for the process of heredity and the wide variety of traits seen among offspring. Despite his mistaken belief in pangenesis, Darwin nonetheless had an enormous impact on human understanding of heredity. During his years of extensive worldwide travel, Darwin collected many observations of how related species adapt to their local environments. Darwin and British naturalist Alfred Wallace independently formulated the theory of natural selection, which holds that members of a given species born with more favorable characteristics to deal with their environment would be most likely to survive to pass on these traits to the next generation. This important theory was popularized by Darwin’s publication On the Origin of Species (1859). The book was an immediate sensation, but it raised many questions. Foremost among these was the mystery of how organisms could appear with modified or entirely new traits.

At roughly the same time that Darwin published his natural selection theories, the answer to many questions about the mechanisms of heredity were being unraveled by Gregor Mendel, a reclusive Austrian monk. Mendel conducted a long series of experiments on pea plants during the 1850s and 1860s. Mendel crossbred plants that expressed differing traits, such as height and flower color. His conclusions from these experiments helped him formulate a comprehensive theory of how such traits pass from one generation to another. In his studies, Mendel recognized that characteristics were inherited as discrete units, and that each of these was inherited independently of the others. He speculated that each parent has pairs of these units but passes only one to an offspring. He also noted that certain forms of one trait were always dominant over others. Today the units that Mendel described are known as genes.

C

Emergence of the Science of Genetics

Mendel published his findings in 1866, but they went largely unnoticed for more than three decades. In the year 1900, however, Dutch botanist Hugo Marie de Vries, German botanist Karl Correns, and Austrian botanist Erich Tschermak independently rediscovered the monk’s works and verified his conclusions.

Advances in cytology, the science of the structure and function of cells, enabled scientists to more deeply appreciate Mendel’s work. In 1902 American biologist Walter S. Sutton and German cell biologist Theodor Boveri separately noted the parallels between Mendel’s units and chromosomes. The demonstration of the chromosomal basis of inheritance gave rise to the modern science of genetics. The term genetics itself was coined in 1905 by British biologist William Bateson. The terms gene and genotype were contributed in 1909 by German scientist Wilhelm Johannsen.

In 1905 American biologists Edmund B. Wilson and Nettie Stevens independently discovered and identified the sex chromosomes. Wilson discovered the X chromosome in a butterfly, and Stevens discovered the Y chromosome in a beetle. The discoveries of the X and Y chromosomes helped scientists begin to unravel new patterns of inheritance. Foremost among this research was the work of American biologist Thomas Hunt Morgan on fruit flies. In 1910 Morgan identified the first proof of a sex-linked trait, an eye-color characteristic that resides on the X chromosome of fruit flies. With this finding, Morgan became the first scientist to pin down the location of a gene to a specific chromosome. Morgan was also the first to explain the implications of linkage, unusual patterns of inheritance that occur when multiple genes found on the same chromosome are inherited together.

A student of Morgan’s, American biologist Alfred Sturtevant, found early evidence of the mechanisms of crossing over, the phenomenon in which chromosomes interchange genes. More definitive proof emerged in the 1930s with work by American geneticists Harriet Creighton and Barbara McClintock. The pair demonstrated gene recombination with experiments on seed color in corn. McClintock later gained notice for her work on transposable elements, large genetic segments that move within a chromosome or even between chromosomes. Her research into these elements, commonly known as jumping genes, earned McClintock the 1983 Nobel Prize in physiology or medicine.

D

Breakthroughs in DNA Studies

While cytologists and geneticists were studying the properties and location of genes on chromosomes, other scientists focused their studies on the composition of genes. In 1928 British microbiologist Frederick Griffith ran a series of experiments on two strains of bacteria, one that kills mice and another that is harmless to them. When Griffith injected mice with killed cells of the virulent bacteria, all of the mice survived. But in a second trial, when Griffith injected a combined cocktail of dead virulent bacteria and live “harmless” bacteria, the mice all died. He concluded that something in the dead virulent cells “transformed” the hereditary material of normally harmless bacteria so that they became killers. Most scientists at the time theorized that the transforming factor was composed of a protein.

The real identity of the transforming factor in this experiment was not identified until 1944, when American geneticists Oswald Avery, Colin MacLeod, and Maclyn McCarty revisited Griffith’s research. After isolating different molecular components from dead bacterial cells, Avery and his colleagues determined that DNA was the agent that transformed the live harmless bacteria into killers.

Despite a growing body of evidence about the function of DNA, many scientists were not ready to reject proteins as the hereditary material. The debate was largely quieted in 1952 by American geneticists Alfred Hershey and Martha Chase. Hershey and Chase showed that when a type of virus called a bacteriophage infects a bacterium, it is the virus’s DNA—not protein—that enters the bacterium to cause infection. Their studies confirmed that DNA contained the virus’s genetic information, which triggered viral replication within the bacteria.

The experiments of Hershey and Chase convinced most scientists that DNA was the molecule of heredity, but many questions about the structure and mechanisms of DNA remained. In the early 1950s researchers began to apply techniques of X-ray diffraction to learn about the basic structure of DNA. X-ray diffraction can determine molecular structures by measuring patterns of scattered X rays after they pass through a crystalline substance. British physical chemist Rosalind Franklin and British biophysicist Maurice Wilkins used X-ray diffraction to obtain DNA images of unprecedented clarity.

Yet the exact three-dimensional structure of DNA remained unclear. The groundbreaking work of American biochemist James Watson and British biophysicist Francis Crick solved that mystery. In 1953 the two proposed a model of DNA that is still accepted today: A double helix molecule formed by two chains, each composed of alternating sugar and phosphate groups, connected by nitrogenous bases. Watson and Crick (along with Wilkins) were awarded the 1962 Nobel Prize in physiology or medicine for their discoveries.

Watson and Crick speculated that the structure of DNA provided some obvious clues about how the molecule could replicate itself. They proposed a replication model in which each strand of DNA serves as a template for making exact copies. This model of replication, called semi-conservative replication, was demonstrated in 1958 by American molecular biologists Matthew Meselson and Franklin Stahl. Their experiments demonstrated the mechanisms of replication by tracking DNA containing a heavy nitrogen isotope through a series of replications.

With DNA’s structure and replication mechanisms largely solved, scientists turned their attention to identifying the genetic code—learning how a gene’s nucleotide sequence determines what type of protein is made. In the late 1950s, South African geneticist Sydney Brenner and other scientists confirmed that RNA acted as an intermediary between DNA and protein production. Researchers still were uncertain how the sequence of nucleotides in DNA corresponded to the production of specific amino acids. In 1961 Crick and Brenner determined that groups of three nucleotides, now known as codons, code for the 20 amino acids that form the foundation of proteins.

The exact relationship between codons and amino acids was clarified after several important discoveries. American biochemists Marshall Nirenberg and J. Heinrich Matthaei synthesized repeated nucleotide sequences that led to the production of repeated single amino acids. They identified how certain codon combinations code for a specific amino acid. A process developed by American geneticist Har Gobind Khorana helped scientists create a “dictionary” of codons that defined specific amino acids, thus resolving the remaining ambiguities in the genetic code. Only 12 years after the structure of DNA was deduced, the genetic code was solved.

	More from Encarta
	•  7 tips for funding an online degree •  How to succeed in the fashion industry without being a top designer •  Presidential Myths Quiz •  Coffee break: Recharge your brain