Genetics For Dummies
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Many milestones define the history of genetics. The events in the world of genetics are listed here roughly in order of historical occurrence.

evolution was a milestone in genetics ©Nasky/

The publication of Darwin’s The Origin of Species

Earthquakes have aftershocks — little mini-earthquakes that rattle around after the main quake. Events in history sometimes cause aftershocks, too. The publication of one man’s life’s work is such an event. From the moment it hit the shelves in 1856, Charles Darwin’s The Origin of Species was deeply controversial (and still is).

The basis of evolution is elegantly simple: Individual organisms vary in their ability to survive and reproduce. For example, a sudden cold snap occurs, and most individuals of a certain bird species die because they can’t tolerate the rapid drop in temperature. But individuals of the same species that can tolerate the unexpected freeze survive and reproduce. As long as the ability to deal with rapid temperature drops is heritable, the trait is passed to future generations, and more and more individuals inherit it. When groups of individuals are isolated from each other, they wind up being subjected to different sorts of events (such as weather patterns). After many, many years, stepwise changes in the kinds of traits that individuals inherit based on events like a sudden freeze accumulate to the point that populations with common ancestors become separate species.

Darwin concluded that all life on earth is related by inheritance in this fashion and, thus, has a common origin. Darwin arrived at his conclusions after years of studying plants and animals all over the world. What he lacked was a convincing explanation for how individuals inherit advantageous traits.

Yet the explanation was literally at his fingertips. Gregor Mendel figured out the laws of inheritance at about the same time that Darwin was working on his book. Apparently, Darwin failed to read Mendel’s paper — he scrawled notes on the papers immediately preceding and following Mendel’s paper but left Mendel’s unmarked. Darwin’s copious notes show no evidence that he was even aware of Mendel’s work.

Even without knowledge of how inheritance works, Darwin accurately summarized three principles that are confirmed by genetics:

  • Variation is random and unpredictable. Studies of mutation confirm this principle.
  • Variation is heritable (it can be passed on from one generation to the next). Mendel’s own research — and thousands of studies over the past century — confirms heritability.
  • Variation changes in frequency over the course of time. For decades, genetic studies have confirmed that genetic variation within populations changes because of things like mutation, accidents, and geographic isolation (to name only a few causes).
Regardless of how you view it, the publication of Darwin’s The Origin of Species is pivotal in the history of genetics. If no genetic variation existed, all life on earth would be precisely identical. Variation gives the world its rich texture and complexity, and it’s what makes you wonderfully unique.

The rediscovery of Mendel’s work

In 1866, Gregor Mendel wrote a summary of the results of his gardening experiments with peas. His work was published in the scientific journal Versuche Pflanzen Hybriden, where it gathered dust for nearly 40 years.

Although Mendel wasn’t big on self-promotion, he sent copies of his paper to two well-known scientists of his time. One copy remains missing; the other was found in what amounts to an unopened envelope — the pages were never cut. (Old printing practices resulted in pages being folded together; the only way to read the paper was to cut the pages apart.) Thus, despite the fact that his findings were published and distributed (though limitedly), his peers didn’t grasp the magnitude of Mendel’s discovery.

Mendel’s work went unnoticed until three botanists — Hugo de Vries, Erich von Tschermak, and Carl Correns — all reinvented Mendel’s wheel, so to speak. These three men conducted experiments that were very similar to Mendel’s. Their conclusions were identical — all three “discovered” the laws of heredity. De Vries found Mendel’s work referenced in a paper published in 1881. (De Vries coined the term mutation, by the way.) The author of the 1881 paper, a man by the name of Focke, summarized Mendel’s findings but didn’t have a clue as to their significance. De Vries correctly interpreted Mendel’s work and cited it in his own paper, which was published in 1900. Shortly thereafter, Tschermak and Correns also discovered Mendel’s publication through de Vries’s published works and indicated that their own independent findings confirmed Mendel’s conclusions as well.

William Bateson is perhaps the great hero of this story. He was already incredibly influential by the time he read de Vries’s paper citing Mendel, and unlike many around him, he recognized that Mendel’s laws of inheritance were revolutionary and absolutely correct. Bateson became an ardent voice spreading the word. He coined the terms genetics, allele (shortened from the original allelomorph), homozygote, and heterozygote. Bateson was also responsible for the discovery of linkage, which was experimentally confirmed later by Morgan and Bridges.

DNA transformation

Frederick Griffith wasn’t working to discover DNA. The year was 1928, and the memory of the deadly flu epidemic of 1918 was still fresh in everyone’s mind. Griffith was studying pneumonia in an effort to prevent future epidemics. He was particularly interested in why some strains of bacteria cause illness and other seemingly identical strains do not.

To get to the bottom of the issue, he conducted a series of experiments using two strains of the same species of bacteria, Streptococcus pneumonia. The two strains looked very different when grown in a Petri dish, because one grew a smooth carpet and the other a lumpy one (he called it “rough”). When Griffith injected smooth bacteria into mice, they died; rough bacteria, on the other hand, were harmless.

To figure out why one strain of bacteria was deadly and the other wasn’t, Griffith conducted a series of experiments. He injected some mice with heat-killed smooth bacteria (which turned out to be harmless) and others with heat-killed smooth in combination with living rough bacteria. This combo proved deadly to the mice. Griffith quickly figured out that something in the smooth bacteria transformed rough bacteria into a killer. But what? For lack of anything better, he called the responsible factor the transforming principle.

Oswald Avery, Maclyn McCarty, and Colin MacLeod teamed up in the 1940s to discover that Griffith’s transforming principle was actually DNA. This trio made the discovery by a dogged process of elimination. They showed that fats and proteins don’t do the trick; only the DNA of smooth bacteria provides live rough bacteria with the needed ingredient to become a killer. Their results were published in 1944, and like Mendel’s work nearly a century before, their findings were largely rejected.

It wasn’t until Erwin Chargaff came along that the transforming principle started to get the appreciation it deserved. Chargaff was so impressed that he changed his entire research focus to DNA. Chargaff eventually determined the ratios of bases in DNA that helped lead to Watson and Crick’s momentous discovery of DNA’s double helix structure.

The discovery of jumping genes

By all accounts, Barbara McClintock was both brilliant and a little odd; a friend once described her as “not fooled or foolable.” McClintock was unorthodox in both her research and her outlook, as she lived and worked alone for most of her life. Her career began in the early 1930s and took her into a man’s world — very few women worked in the sciences in her day.

In 1931, McClintock collaborated with another woman, Harriet Creighton, to demonstrate that genes are located on chromosomes. This fact sounds so self-evident now, but back then, it was a revolutionary idea. McClintock’s contribution to genetics goes beyond locating genes on chromosomes, though. She also discovered traveling bits of DNA, sometimes known as jumping genes.

In 1948, McClintock, working independently, published her results demonstrating that certain genes in corn could hop around from one chromosome to another without translocation. Her announcement triggered little reaction at first. It’s not that people thought McClintock was wrong; she was just so far ahead of the curve that her fellow geneticists couldn’t comprehend her findings. Alfred Sturtevant (who was responsible for the discovery of gene mapping) once said, “I didn’t understand one word she said, but if she says it is so, it must be so!”

Now referred to as transposable elements or transposons, scientists have since discovered that there are many different types. It is also now known that up to half of the human genome contains sequences from transposable elements. However, many of these are basically ancient relics that are no longer able to jump. And many others are rendered silent by certain genetic mechanisms. For those that are still active and able to move, the effect depends on where they land. If they land within a gene, they can cause a mutation that results in disease. In other cases, their movement can contribute to genetic diversity and evolution of the species. The frequency with which transposons move depends on the species and the type of transposon.

It took nearly 40 years before the genetics world caught up with Barbara McClintock and awarded her the Nobel Prize in Physiology or Medicine in 1983. By then, jumping genes had been discovered in many organisms. Feisty to the end, this grand dame of genetics passed away in 1992 at the age of 90.

The birth of DNA sequencing

So many events in the history of genetics lay a foundation for other events to follow. Frederick Sanger’s invention of chain-reaction DNA sequencing is one of those foundational events. In 1980, Sanger shared the Nobel Prize in Chemistry with Walter Gilbert for their work on DNA.

Sanger figured out how to use the characteristics of DNA and of DNA replication to determine the sequence of DNA. Chain-termination sequencing, as Sanger’s method is called, uses the same mechanics as replication in your cells. Sanger figured out that he could control the DNA building process by snipping off one oxygen molecule from the building blocks of DNA. The resulting method allowed identification of every base, in order, along a DNA strand, sparking a revolution in the understanding of how your genes work. This process is responsible for the Human Genome Project, DNA fingerprinting, genetic engineering, and gene therapy.

The invention of PCR

In 1985, while driving along a California highway in the middle of the night, Kary Mullis had a brainstorm about how to carry out DNA replication in a tube. His idea led to the invention of polymerase chain reaction (PCR), a pivotal point in the history of genetics.

In essence, PCR acts like a copier for DNA. Even the tiniest snippet of DNA can be copied. Scientists need many copies of a DNA molecule before enough is present for them to examine. Without PCR, large amounts of DNA are needed to generate a DNA fingerprint. However, at many crime scenes, only tiny amounts of DNA are present. PCR is the powerful tool that every crime lab in the country now uses to detect the DNA left behind at crime scenes and to generate DNA fingerprints.

Mullis’s bright idea turned into a billion-dollar industry. Although he reportedly was paid a paltry $10,000 for his invention (from the lab where he worked), he received the Nobel Prize for Chemistry in 1993 (a sort of consolation prize).

The development of recombinant DNA technology

In 1970, Hamilton O. Smith discovered restriction enzymes, which act as chemical cleavers to chop DNA into pieces at very specific sequences. As part of other research, Smith put bacteria and a bacteria-attacking virus together. The bacteria didn’t go down without a fight — instead, it produced an enzyme that chopped the viral DNA into pieces, effectively destroying the invading virus altogether. Smith determined that the enzyme, now known as HindII (named for the bacteria Haemophilus influenzae Rd), cuts DNA every time it finds certain bases all in a row and cuts between the same two bases every time.

This fortuitous (and completely accidental!) discovery was just what was needed to spark a revolution in the study of DNA. Some restriction enzymes make offset cuts in DNA, leaving single-stranded ends. The single-strand bits of DNA allow geneticists to “cut-and-paste” pieces of DNA together in novel ways, forming the entire basis of what’s now known as recombinant DNA technology.

Gene therapy, the creation of genetically engineered organisms, and practically every other advance in the field of genetics these days all depend on the ability to cut DNA into pieces without disabling the genes and then to put the genes into new places — a feat made possible thanks to restriction enzymes.

Researchers have used thousands of restriction enzymes to help map genes on chromosomes, study gene function, and manipulate DNA for diagnosis and treatment of disease. Smith shared the Nobel Prize in Physiology or Medicine in 1978 with two other geneticists, Dan Nathans and Werner Arber, for their joint contributions to the discovery of restriction enzymes.

The invention of DNA fingerprinting

Sir Alec Jeffreys has put thousands of wrongdoers behind bars. Almost single-handedly, he’s also set hundreds of innocent people free from prison. Not bad for a guy who spent most of his time in the genetics lab.

Jeffreys invented DNA fingerprinting in 1985. By examining the patterns made by human DNA after it was diced up by restriction enzymes, Jeffreys realized that every person’s DNA produces a slightly different number of various sized fragments (which number in the thousands).

Jeffreys’s invention has seen a number of refinements since its inception. PCR and the use of STRs (short tandem repeats) have replaced the use of restriction enzymes. Modern methods of DNA fingerprinting are highly repeatable and extremely accurate, meaning that a DNA fingerprint can be stored much like a fingerprint impression from your fingertip. Crime laboratories all over the United States make use of the methods that Jeffreys pioneered, and the information that these labs generate is housed in a huge database hosted by the FBI. This data can then be accessed by police departments in order to help match criminals to crimes. In 1994, Queen Elizabeth II knighted Jeffreys for his contributions to law enforcement and his accomplishments in genetics.

The birth of developmental genetics

Every cell in your body has a full set of genetic instructions to make all of you. The master plan of how an entire organism is built from genetic instructions remained a mystery until 1980, when Christiane Nüsslein-Volhard and Eric Wieschaus identified the genes that control the whole body during fly development.

Fruit flies and other insects are constructed of interlocking pieces, or segments. A group of genes (collectively called segmentation genes) tells the cells which body segments go where. These genes, along with others, give directions like top and bottom and front and back, as well as the order of body regions in between. Nüsslein-Volhard and Wieschaus made their discovery by mutating genes and looking for the effects of the “broken” genes. When segmentation genes get mutated, the fly ends up lacking whole sections of important body parts or certain pairs of organs.

A different set of genes (called homeotic genes) controls the placement of all the fly’s organs and appendages, such as wings, legs, eyes, and so on. One such gene is eyeless. Contrary to what would seem logical, eyeless actually codes for normal eye development. Using the same recombinant DNA techniques made possible by restriction enzymes, Nüsslein-Volhard and Wieschaus moved eyeless to different chromosomes where it could be turned on in cells in which it was normally turned off. The resulting flies grew eyes in all sorts of strange locations — on their wings, legs, butts, you name it. This research showed that, working together, segmentation and homeotic genes put all the parts in all the right places. Humans have versions of these genes, too; your body-plan genes were discovered by comparing fruit fly genes to human DNA.

The work of Francis Collins and the Human Genome Project

In 1989, Francis Collins and Lap-Chee Tsui identified the single gene responsible for cystic fibrosis. The very next year, the Human Genome Project (HGP) officially got underway. Collins, who has both a medical degree and a PhD in physical chemistry, later replaced James Watson as the head of the National Human Genome Research Institute in the United States and supervised the race to sequence the entire human genome from start to finish. In 2009, Collins became the director of the U.S. National Institutes of Health.

Collins is one of the true heroes of modern genetics. He kept the HGP ahead of schedule and under budget. He continues to champion the right to free access to all the HGP data, making him a courageous opponent of gene patents and other practices that restrict access to discovery and healthcare, and he’s a staunch defender of genetic privacy. Although the human genome is still bits and pieces away from being completely sequenced, the project wouldn’t have been a success without the tireless work of Collins.

About This Article

This article is from the book:

About the book authors:

Tara Rodden Robinson, PhD, was an instructor and Postdoctoral Fellow in Genetics in the Department of Biological Sciences at Auburn University. She has also been an instructor at Oregon State University. Lisa Cushman Spock, PhD, CGC, is a clinical genomics specialist and former genetics counselor at Indiana University School of Medicine.

Tara Rodden Robinson, PhD, was an instructor and Postdoctoral Fellow in Genetics in the Department of Biological Sciences at Auburn University. She has also been an instructor at Oregon State University. Lisa Cushman Spock, PhD, CGC, is a clinical genomics specialist and former genetics counselor at Indiana University School of Medicine.

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