Genetics

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Genetics

Genetics is the branch of biology concerned with the science of heredity, or the transfer of specific characteristics from one generation to the next. Genetics focuses primarily on genes, coded units found along the DNA molecules of the chromosomes, housed by the cell nucleus. Together, genes make up the blueprints that determine the entire development of the species of organisms down to specific traits, such as the color of eyes and hair. Geneticists are concerned with three primary areas of gene study: how genes are expressed and regulated in the cell, how genes are copied and passed on to successive generations, and what are the genetic basis for differences between the species. Although the science of genetics dates back at least to the nineteenth century, little was known about the exact biological makeup of genes until the 1940s. Since that time, genetics has moved to the forefront of biological research. Scientists are now on the verge of identifying the location and function of every gene in the entire human genome . The result will not only be a greater understanding of the human body, but new insights into the origins of disease and the formulation of possible treatments and cures.

The history of genetics

Although humans have known about inheritance for thousands of years, the first scientific evidence for the existence of genes came in 1866, when the Austrian monk and scientist Gregor Mendel published the results of a study of hybridization of plants—the combining of two individual species with different genetic make-ups to produce a new individual. Working with pea plants with specific characteristics such as height (tall and short) and color (green and yellow), Mendel bred one type of plant for several successive generations. He found that certain characteristics appeared in the next generation in a regular pattern. From these observations, he deduced that the plants inherited a specific biological unit (which he called factors (now called alleles ), genes determining different forms of a single characteristic) from each parent. Mendel also noted that when factors or alleles pair up, one is dominant (which means it determines the trait, like tallness) while the other is recessive (which means it has no bearing on the trait). It is now understood that alleles may be single genes or sets of genes working together, each contributing to the final form of a physical characteristic (multiple allelism).

The period of classical genetics, in which researchers had no knowledge of the chemical constituents in cells that determine heredity, lasted well into the
twentieth century. However, several advances made during that time contributed to the growth of genetics. In the eighteenth century, scientists used the relatively new technology of the microscope to discover the existence of cells, the basic structures in all living organisms. By the middle of the nineteenth century, they had discovered that cells reproduce by dividing.

Although Mendel laid the foundation of genetics, his work began to take on true significance in 1903 when Theodore Boveri and Walter Sutton independently proposed a chromosomal theory of inheritance. They discovered that chromosomes during gamete production behave like the so-called Mendel's particles behave. In 1910, Thomas Hunt Morgan (1866–1946) confirmed the existence of chromosomes through experiments with fruit flies . He also discovered a unique pair of chromosomes called the sex chromosomes, which determined the sex of offspring. Morgan deduced that specific genes reside on chromosomes from his observation that an X-shaped chromosome was always present in flies that had white eyes. A later discovery showed that chromosomes could mutate or change structurally, resulting in a change in characteristics which could be passed on to the next generation.

More than three decades passed before scientists began to delve into the specific molecular and chemical structures that make up chromosomes. In the 1940s, a research team led by Oswald Avery (1877–1955) discovered that deoxyribonucleic acid (DNA) was responsible for transformation of non-pathogenic bacteria into pathogenic ones. The final proof that DNA was the specific molecule that carries genetic information was made by Alfred Hershey and Martha Chase in 1952. They used radioactive label to differentiate between viral protein and DNA, proving that over 80% of viral DNA entered bacterial cell causing infection , while protein did not cause infection.

The most important discovery in genetics occurred in 1953, when James Watson and Francis Crick solved the mystery of the exact structure of DNA. The two scientists used chemical analyses and x-ray diffraction studies performed by other scientists to uncover the specific structure and chemical arrangement of DNA. X-ray diffraction is a procedure in which parallel x-ray beams are diffracted by atoms in patterns that reveal the atoms' atomic weight and spatial arrangement. A month after their double-helix model of DNA appeared in scientific journals, the two scientists showed how DNA replicated. Armed with these new discoveries, geneticists embarked on the modern era of genetics, including efforts like genetic engineering , gene therapy , and a massive project to determine the exact location and function of all of the more than 100,000 genes that make up the human genome.

The biology of genetics

Genetic information is contained in the chromosomes, threadlike structures composed of DNA, and present in the nuclei of all cell types and are passed to daughter cells during cell division . Multicellular organisms contain two types of cells—body cells (or somatic cells) and germ cells (or reproductive cells). Germ cells are the ones that pass on the genetic information to the progeny. In contrast to somatic cells that contain dual copies of chromosomes in each cell, germ cells replicate through a process called meiosis , which ensures that the germ cells have only a single set of chromosomes, a condition called haploidy (designated as n). The somatic cells of humans have 23 pairs of chromosomes (46 chromosomes overall), a condition known as diploid (or 2n). Through the process of meiosis, a new cell, called a haploid gamete, is created with only 23 chromosomes: this is either the sperm cell of the father or the egg cell of the mother. The fusion of egg and sperm restores the diploid chromosome number in the zygote. This cell carries all the genetic information needed to grow into an embryo and eventually a full grown human with the specific traits and attributes passed on by the parents. Offspring of the same parents differ because the sperm cells and egg cells vary in their gene sequences , due to random recombination.

The somatic, or body cells are the primary components of functioning organisms. The genetic information in these cells is passed on through a process of cell division called mitosis . Unlike meiosis, mitosis is designed to transfer the identical number of chromosomes during cell regeneration or renewal. This is how cells grow and are replaced in exact replicas to form specific tissues and organs, such as muscles and nerves. Without mitosis, an organism's cells would not regenerate, resulting not only in cell death , but possible death of the entire organism . (It is important to note that some organisms reproduce asexually by mitosis alone.)

The genetic code

To understand genes and their biological function in heredity, it is necessary to understand the chemical makeup and structure of DNA. Although some viruses carry their genetic information in the form of ribonucleic acid (RNA) , most higher life forms carry genetic information in the form of DNA, the molecule that makes up chromosomes.

The complete DNA molecule is often referred to as the blueprint for life because it carries all the instructions, in the formation of genes, for the growth and functioning of most organisms. This fundamental molecule is similar in appearance to a spiral staircase, which is also called a double helix . The sides of the DNA double helix ladder are made up of alternate sugar and phosphate molecules, like links in a chain. The rungs, or steps, of DNA are made from a combination of four nitrogen-containing bases—two purines (adenine [A] and guanine [G]) and two pyrimidines (cytosine [C] and thymine [T]). The four letters designating these bases (A, G, C, and T) are the alphabet of the genetic code. Each rung of the DNA molecule is contains a combination of two of these letters, one jutting out from each side. In this genetic code, A always combines with T, and C with G to make what is called a base pair. Specific sequences of these base pairs, which are bonded together by atoms of hydrogen , make up the genes.

While a four-letter alphabet may seem rather small for constructing the comprehensive vocabulary that describes and determines the myriad life forms on Earth , the sequences or order of these base pairs are nearly limitless. For example, various sequences or rungs that make up a simple six base gene could be ATCGGC, or TAATCG, or AGCGTA, or ATTACG, and so on. Each one of these combinations has a different meaning. Different sequences provide the code not only for the type of organism, but also for specific traits like brown hair and blue eyes. The more complex an organism, from bacteria to humans, the more rungs or genetic sequences appear on the ladder. The entire genetic makeup of a human, for example, may contain 120 million base pairs, with the average gene unit being 2,000 to 200,000 base pairs long. Except for identical twins, no two humans have exactly the same genetic information.

Genetic information is duplicated during the process of DNA replication , which begins a few hours before the initiation of cell division (mitosis). To produce identical genetic information during mitosis, the hydrogen bonds holding together the two halves of the DNA ladder unzip, in presence of proteins called helicases, to expose single strands of DNA. These old strands act as templates to make new DNA molecules. Replication is initiated by this separation of DNA, and requires short DNA fragments (primers) to start synthesis of a new DNA strand by specific cellular enzymes called DNA polymerases. DNA rarely mutates during replication, as the proofreading and "repair" enzymes make sure that any errors are quickly repaired to protect the accuracy of the genetic information. Once completed, each new half of the DNA ladder has the identical information as the old one. This is achieved by the fact that T always combines with A and C with G, therefore if the template had a sequence ATGCTG the newly made second strand will be TACGAC. When cell mitosis is completed, each new cell contains an exact replica of the DNA.

Cells contain hundreds of different proteins and its functions are dependent on which of the thousands of types of different proteins it contains. Proteins are made up of chains of amino acids. The arrangement of the amino acids to build specific proteins is determined by the basepair sequence contained or encoded in DNA. This genetic information has to be converted to proteins building over half of all solid body tissues and control most biological processes within and among these tissues. This is achieved by using the genetic code, which is a set of 64 triplets of bases (called codons ) corresponding to each amino acid and the initiation and termination signals for protein synthesis.

As the sites of protein production lie outside the cell nucleus, the instructions for making them have to be transported out of the nucleus. The messenger that carries these instructions is messenger RNA, or mRNA (a single stranded molecule that has a mirror image of the base pairs on the DNA). mRNA is made in the nucleus during a process called transcription and a single molecule of RNA carries instructions for making only one protein. After being exported out of the nucleus it is transported to ribosomes , which are the protein factories in the cell. In ribosomes the information from mRNA is decoded to produce a protein. This process is called translation. The flow of information is only one way from DNA to RNA and to protein. Therefore characteristics acquired during an organism's life, such as larger muscles or the ability to play the piano, cannot be inherited. However, people may have genes that make it easier for them to acquire these traits through exercise or practice.

Dominant and recessive traits

The expression of the products of genes is not equal, and some genes will override others in expressing themselves as an inherited characteristic. The offspring of organisms that reproduce sexually contain a set of chromosome pairs, half from the father and half from the mother. However, normally people do not have one blue eye and one brown eye, or half brown hair and half blond hair because most genetic traits are the result of the expression of either the dominant or the recessive genes. If a dominant and a recessive gene appear together (the heterozygous condition), the dominant will always win, producing the trait it is coded for. The only time a recessive trait (such as the one for blond hair) expresses itself is when two recessive genes are present (the homozygous condition). As a result, parents with heterozygous genes for brown hair could produce a child with blond hair if the child inherits two recessive blond-hair genes from the parents. The genes residing in the chromosome's DNA can also be present in alternative forms called alleles. It is important to note that some characteristics are a result of presence of various alleles, e.g. pink snapdragon flowers or blood types.

This hereditary law also holds true for genetic diseases. Neither parent may show signs of a genetic disease, caused by a defective gene, but they can pass the double-recessive combination on to their children. Some genetic diseases are dominant and others are recessive. Dominant genetic defects are more common because it only takes one parent to pass on a defective allele. A recessive genetic defect requires both parents to pass on the recessive allele that causes the disease. A few inherited diseases (such as Down syndrome ) are caused by abnormalities in the number of chromosomes, where the offspring has 47 chromosomes instead of the normal 46.

Genetic recombination and mutations

The DNA molecule is extremely stable, ensuring that offspring have the same traits and attributes that will enable them to survive as well as their parents. However, a certain amount of genetic variation is necessary if species are to adapt by natural selection to a changing environment. Often, this change in genetic material occurs when chromosome segments from the parents physically exchange segments with each other during the process of meiosis. This is known as cross over or intrinsic recombination.

Genes can also change by mutations on the DNA molecule, which occur when a mutagen alters the chemical or physical makeup of DNA. Mutagens include ultraviolet light and certain chemicals. Genetic mutations in somatic (body) cells result in malfunctioning cells or a mutant organism. These mutations result from a change in the base pairs on the DNA, which can alter cell functions and even give rise to different traits. Somatic cell mutations can result in disfigurement, disease, and other biological problems within an organism. These mutations occur solely within the affected individual.

When mutations occur in the DNA of germ (reproductive) cells, these altered genes can be passed on to the next generation. A germ cell mutation can be harmful or result in an improvement, such as a change in body coloring that acts as camouflage. If the trait improves an individual organism's chances for survival within a particular environment, it is more likely to become a permanent trait of the species because the offspring with this gene would have a greater chance to survive and pass on the trait to succeeding generations.

Mutations are generally classified into two groups, spontaneous mutations and induced mutations. Spontaneous mutations occur naturally from errors in coding during DNA replication. Induced mutations come from outside influences called environmental factors. For example, certain forms of radiation can damage DNA and cause mutations. A common example of this type of mutating agent is the ultraviolet rays of the sun , which can cause skin cancer in some people who are exposed to intense sunlight over long periods of time. Other mutations can occur due to exposure to man-made chemicals. These types of mutations modify or change the chemical structure of base pairs.

Population genetics

Population genetics is the branch of genetics that focuses on the occurrence and interactions of genes in specific populations of organisms. One of its primary concerns is evolution , or how genes change from one generation to the next. By using mathematical calculations that involve an interbreeding population's gene pool (the total genetic information present in the individuals within the species), population geneticists delve into why similar species vary among different populations that may, for example, be separated by physical boundaries such as bodies of water or mountains .

As outlined in the previous section, genetic mutations may cause changes in a population if the mutation occurs in the germ cells. Many scientists consider mutation to be the primary cause of genetic change in successive generations. However, population geneticists also study three other factors involved in genetic change or evolution: migration , genetic drift, and natural selection.

Migration occurs when individuals within a species move from one population to another, carrying their genetic makeup with them. Genetic drift is a natural mechanism for genetic change in which specific genetic traits coded in alleles (alternate states of functioning for the same gene) may change by chance often in a situation where organisms are isolated, as on an island .

Natural selection, a theory first proposed by Charles Darwin in 1858, is a process that occurs over successive generations. The theory states that genetic changes that enhance survival for a species will come to the forefront over successive generations because the gene carriers are better fit to survive and are more likely reproduce, thus establishing a new gene pool, and eventually, perhaps, an entirely new species. One proposed mechanism of natural selection is gradualism, which predicts very slow and steady accumulation of beneficial genes. Punctuated equilibrium , in contrast, depicts natural selection as occurring in brief, but accelerated periods of "survival of the fittest" with lengthy periods of relative stagnation of genetic change in populations. Some scientists hold that both processes occur and have occurred.

Genetics and the golden age of biology

More than any other biological discipline, genetics is responsible for the most dramatic breakthroughs in biology and medicine today. Scientists are rapidly advancing in their ability to engineer genetic material to achieve specific characteristics in plants and animals. The primary way to genetically engineer DNA is called gene cloning, in which a segment of one DNA molecule is removed and then inserted, into another DNA molecule. This process takes advantage of restriction enzymes to cut DNA into fragments of different lengths and ligase to re-create new molecules. Restriction enzymes act as molecular scissors, cutting larger molecules (like DNA) at specific sites. The ends of these fragments are "sticky" in that they have an affinity for complimentary ends of other DNA fragments. DNA ligase acts as a glue to join the ends of the two molecules together. This approach has applications in agriculture and medicine.

In agriculture, genetic engineering is used to produce transgenic animals or plants, in which genes are transferred from one organism to another. This approach has been used to reduce the amount of fat in cattle raised for meat, or to increase proteins in the milk of dairy cattle that favor cheese making. Fruits and vegetables have also been genetically engineered so they do not bruise as easily, or so they have a longer shelf life. On the other hand, in medicine, genetic engineering provided great advancements in production of antibiotics , hormones , vaccines, understanding disease mechanisms and in therapy. Gene therapy is currently being developed and used as it provides the opportunity to introduce specific genes into the body to either correct a genetic defect or to enhance the body's capabilities to fight off disease and repair itself. Because many inherited or genetic diseases are caused by the lack of an enzyme or protein, scientists hope to one day treat the unborn by inserting genes to provide the missing enzyme.

Genetic fingerprinting (DNA typing) is based on each individual's unique genetic code. To identify parentage, diagnose inherited diseases in prenatal laboratories or the presence of someone at a crime, scientists use molecular biology techniques such as DNA fingerprinting by applying restriction fragment length polymorphisms (RFLPs) analysis (identifying the characteristic patterns in DNA cut with the restriction enzymes), microsattelite analysis (looking at the small specific DNA sequences), DNA hybridization, DNA sequencing or polymerase chain reaction (PCR ). Development of PCR allows to analyse small amounts of DNA acquired from hair, semen, blood, fingernail fragments, or fetal cells by utilizing DNA polymerase enzyme (the same enzyme used naturally by cells in mitosis) to create identical copies of a DNA molecules from small samples.

One of the most exciting recent developments in genetics is the initiation of the Human Genome Project (HGP). This project is designed to provide a complete genetic road map outlining the location and function of the 100,000 or so genes found in human cells encoded in over three billion bases. The first human genome draft sequences were published in February 2001 by the Celera company and the HGP consortium in the journals Science and Nature, respectively. As a result, genetic researchers will have easy access to specific genes to study how the human body works and to develop therapies for diseases. Gene maps for other species of animals are also being developed.

Future of genetics

Full sequencing of many bacterial genomes, yeast , Caenorhabditis elegans, Drosophila, mouse, and human genomes has brought about a new era in genetics, and a development of a new area—genomics. Availability of full DNA sequences of multiple organisms allows the comparative analysis (comparative genetics) of genomes allowing gene identification, finding of regulatory sequences and tracing evolution.

Genetic analysis proved very successful in Mendelian diseases. New challenges for genetics are the studies of common complex diseases such as asthma , obesity orhypertension . These diseases are caused by interaction of multiple genes and also environment, making their analysis even more difficult. Geneticists analyze DNA sequence to correlate any changes with the disease (association studies). Small fragments of repetitive DNA sequence (microsatellites) or single nucleotide polymorphisms (SNPs) are analyzed. Such studies require analysis of large control (healthy) population in addition to the affected group before any conclusions can be made. Solving of the puzzle of complex traits is going to be possible by combining molecular genetics, biostatistics, further clinical and computational/bioinformatical analysis.

Ethical questions and the future of genetics

Despite the promise of genetics research, many ethical and philosophical questions arise. Many of the concerns about this area of research focus on the increasing ability to manipulate genes. There is a fear that the results will not always be beneficial. For example, some fear that a genetically re-engineered virus could turn out to be extremely virulent, or deadly, and may spread if there is no way to stop it.

Another area of concern is the genetic engineering of human traits and qualities. The goal is to produce people with specific traits such as better health, improved looks, or even high intelligence. While these traits may seem to be desirable on the surface, the concern arises about who will decide exactly what traits are to be engineered into human offspring, and whether everyone will have equal access to an expensive technology. Some fear that the result could be domination by a particular socioeconomic group.

Despite these fears and concerns, genetic research continues. In an effort to ensure that the science is not abused in ways harmful to society, governments in the United States and abroad have created panels and organizations to oversee genetic research. For the most part, international committees composed of scientists and ethical experts state that the benefits of genetic research for medicine and agriculture far outweigh the possible abuses.

Resources

books

Beurton, Peter, Raphael Falk, Hans-Jörg Rheinberger., eds. The Concept of the Gene in Development and Evolution. Cambridge, UK: Cambridge University Press, 2000.

Edlin, Gordon. Human Genetics. Boston: Jones and Bartlett, 1990.

Jacob, François. Logic of Life: A History of Heredity. New York: Random House, 1982.

Thro, Ellen. Genetic Engineering: Shaping the Material of Life. New York: Facts On File, 1993.

periodicals

Brookes, Anthony. "Rethinking Genetic Strategies to Study Complex Diseases." Trends in Molecular Medicine (November 2001): 512–6.

Brownlee, Shannon, and Joanne Silberne, "The Age of Genes." U.S. News & World Report. (4 November 1991): 64–72.

Guo, Sun-Wei, and Kenneth Lange, "Genetic Mapping of Complex Traits: Promises, Problems, and Prospects." Theoretical Population Biology (February 2000): 1–11.

Philips, Tamara J., and John K. Belknap, "Complex-trait Genetics: Emergence of Multivariate Strategies." Nature Reviews. Neuroscience (June 2002):478–485

Tijan, Robert. "Molecular Machines That Control Genes." Scientific American. (February 1995): 54–61.

other

National Institutes of Health. "Guide to the Human Genome" [cited October 19, 2002]. <http://www.ncbi.nlm.nih.gov/genome/guide/human/>.

David Petechuk

KEY TERMS

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Allele: —Any of two or more alternative forms of a gene that occupy the same location on a chromosome.
Amino acid: —An organic compound whose molecules contain both an amino group (-NH2) and a carboxyl group (-COOH). One of the building blocks of a protein.
Base: —A chemical unit that makes up part of the DNA molecule. There are four bases: adenine (A) and guanine (G), which are purines, and cytosine (C) and thymine (T), which are pyrimidines.
Chromosomes: —he structures that carry genetic information in the form of DNA. Chromosomes are located within every cell and are responsible for directing the development and functioning of all the cells in the body.
DNA: —Deoxyribonucleic acid; the genetic material in a cell. Chromosomes are made of DNA.
Dominant (dominant gene): —An allele of a gene that results in a visible phenotype if expressed in a heterozygote.
Gene: —A discrete unit of inheritance, represented by a portion of DNA located on a chromosome. The gene is a code for the production of a specific kind of protein or RNA molecule, and therefore for a specific inherited characteristic.
Genetic recombination: —New configurations produced when two DNA molecules are broken and rejoined together during meiosis.
Heredity: —Characteristics passed on from parents to offspring.
Heterozygous: —Two different forms of the same allele pair on the chromosome.
Homozygous: —Two identical forms of the same allele pair on the chromosome.
Meiosis: —The process of cell division in germ or reproductive cells, producing haploid genetic material.
Mitosis: —The process of cell division in somatic, or body, cells, producing no change in genetic material.
Proteins: —Macromolecules made up of long sequences of amino acids. They make up the dry weight of most cells and are involved in structures, hormones, and enzymes in muscle contraction, immunological response, and many other essential life functions.
Recessive: —Refers to the state or genetic trait that only can express itself when two genes, one from both parents, are present and coded for the trait, but will not express itself when paired with a dominant gene. (See Dominant; Allele)
Ribonucleic acid: —RNA; the molecule translated from DNA in the nucleus that directs protein synthesis in the cytoplasm; it is also the genetic material of many viruses.
Transcription: —The process of synthesizing RNA from DNA.