the importance of genetics we all possess genes that influence our lives. they affect our height and...

The Importance of GeneticsWe all possess genes that influence our lives. They affect our

height and weight, our hair color and skin pigmentation. They influence our susceptibility to many diseases and disorders and even contribute to our intelligence and personality. Genes are fundamental to who and what we are.

Although the science of genetics is relatively new, people have understood the hereditary nature of traits and have “practiced” genetics for thousands of years.

Divisions of Genetics

Traditionally, the study of genetics has been divided intothree major subdisciplines: 1. transmission genetics2. molecular genetics3. population genetics

It is convenient and traditional to divide the study of genetics into these three groups, but we should recognize that the fields overlap and that each major subdivision can be further divided into a number of more specialized fields, such as chromosomal genetics, biochemical genetics, quantitative genetics, and so forth. Genetics can alternatively be subdivided by organism (fruit fly, corn, or bacterial genetics), and each of these organisms can be studied at the level of transmission, molecular, and population genetics.

A Brief History of GeneticsThe first evidence that humans understood and applied the principles of heredity is found in the domestication of plants and animals, which began between approximately 10,000 and 12,000 years ago. By 4000 years ago, sophisticated genetic techniques were already in use in the Middle East. Assyrians and Babylonians developed several hundred varieties of date palms that differed in fruit size, color, taste, and time of ripening. An Assyrian bas-relief from 2880 years ago depicts the use of artificial fertilization to control crosses between date palms

A Brief History of GeneticsAncient writings demonstrate that early humans were aware of

their own heredity. Hindu sacred writings dating to 2000 years ago attribute many traits to the father and suggest that differences between siblings can be accounted for by effects from the mother.

The Talmud, the Jewish book of religious laws based on oral traditions dating back thousands of years, presents an uncannily accurate understanding of the inheritance of hemophilia. It directs that, if a woman bears two sons who die of bleeding after circumcision, any additional sons that she bears should not be circumcised; nor should the sons of her sisters be circumcised, although the sons of her brothers should. This advice accurately depicts the X-linked pattern of inheritance of hemophilia The ancient Greeks gave careful consideration to human reproduction and heredity.

A Brief History of Genetics

The Greek physician Alcmaeon (circa 520 B.C.) conducted dissections of animals and proposed that the brain was not only the principle site of perception, but also the origin of semen. This proposal sparked a long philosophical debate about where semen was produced and its role in heredity. The debate culminated in the concept of pangenesispangenesis, which proposed that specific particles, later called gemmulesgemmules, carry information from various parts of the body to the reproductive organs, from where they are passed to the embryo at the moment of conception. Although incorrect, the concept of pangenesis was highly influential and persisted until the late 1800s

A Brief History of GeneticsPangenesisPangenesis led the ancient Greeks to propose the notion of the

inheritance of acquired characteristics, in which traits acquired during one’s lifetime become incorporated into one’s hereditary information and are passed on to offspring; for example, people who developed musical ability through diligent study would produce children who are innately endowed with musical ability. The notion of the inheritance of acquired characteristics also is no longer accepted, but it remained popular through the twentieth century.

The Greek philosopher Aristotle (384 – 322 B.C.) was keenly interested in heredity. He rejected the concepts of both pangenesis and the inheritance of acquired characteristics, pointing out that people sometimes resemble past ancestors more than their parents and that acquired characteristics such as mutilated body parts are not passed on. Aristotle believed that both males and females made contributions to the offspring and that there was a struggle of sorts between male and female contributions.

The Rise of Modern Genetics

According to preformationismpreformationism, inside the egg or sperm existed a iny miniature adult, a homunculus, which simply enlarged during development. OvistsOvists argued that the homunculus resided in the egg, whereas spermists insisted that it was in the sperm.

Another early notion of heredity was blending inheritanceblending inheritance, which proposed that offspring are a blend, or mixture, of parental traits. This idea suggested that the genetic material itself blends. Once blended, genetic differences could not be separated out in future generations, just as green paint cannot be separated out into blue and yellow pigments.

Modern GeneticsNehemiah Grew (1641–1712) reported that

plants reproduce sexually by using pollen from the male sex cells. Developments in cytology (the study of cells) in the 1800s had a strong influence on genetics. Robert Brown described the cell nucleus in 1833. Building on the work of others, Matthis Jacob Schleiden and Theodor Schwann proposed the concept of the cell theory in 1839.

Charles Darwin one of the most influential biologists of the nineteenth century, put forth the theory of evolution through natural selection and published his ideas in On the Origin of Species in 1856. Walter Flemming observed the division of chromosomes in 1879 and published a superb description of mitosis. By 1885, it was generally recognized that the nucleus contained the hereditary information.

Modern GeneticsThe year 1900 was a watershed in the history of genetics.

Gregor Mendel’s pivotal 1866 publication on experiments with pea plants, which revealed the principles of heredity, was “rediscovered”

Walter Sutton 1902 - genes are located on chromosomesThomas Hunt Morgan - the first genetic mutant of fruit flies in

1910 and used fruit flies to unravel many details of transmission genetics

Ronald A. Fisher, John B. S. Haldane, and Sewall Wright - foundation for population genetics in the 1930s

Geneticists began to use bacteria and viruses in the 1940sJames Watson and Francis Crick - described the three-

dimensional structure of DNA in 1953 By 1966, the chemical structure of DNA and the system by

which it determines the amino acid sequence of proteins had been worked out. Advances in molecular genetics led to the first recombinant DNA experiments in 1973

Walter Gilbert and Frederick Sanger - developed methods for sequencing DNA in 1977

The polymerase chain reaction, a technique for quickly amplifying tiny amounts of DNA, was developed by Kary Mullis and others in 1986.

CELLS and MACROMOLECULES

Bacteria have a plasma membrane (usually enclosed in a rigid cell wall), a single,major circular chromosome, but not intracellular compartments. They may beunicellular or multicellular.

Prokaryotes

Prokaryotes with two subdivisions, Bacteria and Archaea, are the simplest livingcells (1-10 µm diameter) present in all environmental niches.

Archaea are structurally similar to bacteria, but probably branched off from eukaryotes after their common ancestor diverged from bacteria. They tend to inhabit extreme environments. Biochemically are closer to bacteria in some ways, but to eukaryotes in others.

Escherichia coli is the best studied bacterium. E. coli has a genome size of 4600 kilobase (kb), sufficient genetic information for about 3000 proteins. Mycoplasma genitalium, the simplest bacterium, has only 580 kb of DNA for 470 proteins.

The archaeon Methanococcus jannaschii has 1740 kb and encodes a maximum of 1738 proteins.


Taxonomically are classified into four kingdoms: animals, plants, fungi and protists (algae and protozoa).

Eukaryotes

Eukaryotes (10-100 µm diameter) are defined by their possession of membrane-enclosed organelles: nuclei, mitochondria, endoplasmic reticulum, lysosomes, etc. These organelles are the sites of distinct biochemical processes.

Plants and many fungi and protists have a rigid cell wall.

In addition to the organelles, the cytoplasm (a highly organized gel) contains the cytoskeleton, an array of protein fibers which controls the shape and movement of the cell, and which organizes many of its metabolic functions.

These protein fibers include: microtubules (tubulin), microfilaments (actin) and intermediate filaments.

Many eukaryotes are multicellular, with group of cells undergoing differentiation during development to form the specialized tissues of the whole organism.


In the case of complex multicellular eukaryotes, the embryonic cells differentiate into highly specialized cells: nerve, muscle, liver, kidney, etc.

Differentiation

After division, the daughter cells may be identical, or they may change their patterns of gene expression to become functionally different from parent cell.

The DNA content remains the same, but the expressed genes have changed.

The formation of spores (prokaryotes and lower eukaryotes) is an example of such cellular differentiation.

Differentiation is regulated by developmental control genes or homeotic genes. Mutations in these genes result in abnormal body plans.

Co-ordination of the activities of the various tissues and organs is controlled by communication between them involving signaling molecules (neurotransmitters, hormones and growth factors) and specific cell-surface receptors.


Endosomes internalize plasma-membrane proteins and soluble materials from the extracellular medium, and they sort them back to the membranes or to lysosomes for degradation.

Eukaryotic cell organelles

All eukaryotic cells contain a nucleus and many other organelles in their cytosols.

Lysosomes contain various acidic hydrolases that degrade depleted or unneeded cellular components and some ingested materials.

The nucleus, mitochondrion, and chloroplast are delimited by two bilayer membranes separated by an inter-membrane space. All other organelles are surrounded by a single membrane.

Peroxisomes contain enzymes that oxidize various organic compounds without the production of ATP. By-products of oxidation are used in biosynthetic reactions.

Secreted proteins and membrane proteins are synthesized on the rough endoplasmic reticulum (RER). Proteins synthesized on RER first move to theGolgi complex, where they are processed and sorted for transport to the cell surface or other destination.


Mitochondria have a highly permeable outer membrane and a protein-rich inner membrane extensively folded. Enzymes in the inner membrane and central matrix perform the terminal stages of sugar and lipid oxidation coupled to ATP synthesis.

Eukaryotic cell organelles

Plant cells contain one or more large vacuoles, which are storage sites for ions and nutrients. Osmotic flow of water into vacuoles generates turgor pressure that pushesthe plasma membrane against the cell wall.

Chloroplasts contain a complex system of thylakoid membranes in their interiors. These membranes contain the pigments and enzymes that absorb light and produce ATP during photosynthesis.

The nucleus houses the genome of a cell. The inner and outer nuclear membranes are fused at numerous nuclear pores, through which materials pass between the nucleus and the cytosol. Outer nuclear membrane is continuous with that of RER.

In the smooth endoplasmic reticulum many of the reactions of lipid biosynthesis and xenobiotic metabolism are carried out.

The glyoxysomes of plants carry out the reactions of the glyoxylate cycle.


Glycosaminoglycans, essential components of the proteoglycans, are linear chains of repeating disaccharides in which one of the monosaccharide units is an amino sugar and one (or both) of the monosaccharide units contains at least one negatively charged sulfate or carboxylate group.

Macromolecules

α-Amylose and cellulose are polymers of glucose linked α(1→4) and β(1→4), respectively. Starch, a storage form of glucose in plants, contains α-amylose and the α(1→6) branched polymer amylopectin. Cellulose is found in plant cell walls.

Glycogen, a branched polymer, is the storage form of glucose in animals. Chitin, a polymer of N-acetylglucosamine, is found in fungal cell walls and arthropod exoskeletons. Mucopolysaccharides are important components of connective tissue.

Proteins are polymers of amino acids, having many structural and functional roles.

Nucleic acids, DNA and RNA, are polymers of nucleotides. Proteins and nucleic acids are essential cell components which stores and express genetic information.

Amylose

Amylopectin

Cellulose

Chitin


Glycoproteins and proteoglycans are generally found on extracellular surfaces and in extracellular spaces.

Macromolecules

Phospholipids and sphingolipids, containing polar group in addition to the fatty acid components, are fundamental constituents of all cell membranes.

Lipid-linked proteins and lipoproteins have lipid and protein parts covalently or noncovalently attached. Glycolipids have both lipid and carbohydrate components.

The enzymes telomerase and ribonuclease P are nucleoproteins involved in the replication of telomeres and maturation of tRNA, respectively.

Triglycerides contain saturated and unsaturated fatty acids and are the major storage lipids both in animals and plants.

Animal triglycerides are solid and plant triglycerides (oils) are liquid.


Cortical spectrin-actin networks are attached to the cell membrane by bivalent membrane-microfilament binding proteins such as ankyrin and band 4.1.

Large macromolecular assemblies - Cytoskeleton

The cytoskeleton provides structural stability for the cell and contributes to cell movement. Some bacteria have a primitive cytoskeleton.

Intermediate filaments are assembled into networks and bundles by various intermediate filament-binding proteins, which also cross-link intermediate filaments to the plasma and nuclear membranes, microtubules, and microfilaments.

Actin bundles form the core of microvilli and other fingerlike projections of the plasma membrane.

Microfilaments are assembled from monomeric actin subunits, microtubules from α and β-tubulin subunits and intermediate filaments from lamin subunits and other tissue specific proteins.

In some animal cells, microtubules radiate out from a single microtubule-organizing center lying at the cell center.

Cilia and flagella are composed of microtubules complexed with dynein and nexin.


Histones neutralize the repulsion between the negative charges of the DNA sugar-phosphate backbone and allow the DNA to be tightly packaged in chromosomes.

Large macromolecular assemblies - Nucleoproteins

Bacterial 70S ribosomes comprise a large 50S subunit, with 23S and 5S RNA molecules and 31 proteins, and a small 30S subunit, with a 16S RNA molecule and 21 proteins.

Viruses are another example of nucleoprotein complexes.

Chromatin is a deoxyribonucleoprotein complex made up of roughly equal amounts of DNA and small basic proteins called histones,

Eukaryotic 80S ribosomes have 60S (28S, 5.8S and 5S RNAs) and 40S (18S RNA) subunits.

Ribosomes are large cytoplasmic ribonucleoprotein complexes which are the sites of protein synthesis.


Membrane proteins may be peripheral (anchored via a lipid or glycosyl phosphatidylinositol) or integral.

Large macromolecular assemblies - Membranes

The lipid bilayer is the structural basis of all biological membranes.

Membrane proteins have a variety of functions: - receptors for signaling molecules (hormones and neurotransmitters); - enzymes for degrading extracellular molecules before uptake of the products; - pores or channels for the selective transport of small, polar ions and molecules; - mediators of cell-cell interactions (mainly glycoproteins).

Proteins are also a major component of cell membranes.

The precise lipid composition varies from cell to cell and from organelle to organelle.

Phospholipids and sphingolipids naturally form a lipid bilayer with the polar groups on the outside and the nonpolar hydrocarbon chains on the inside.

PROTEIN STRUCTURE & FUNCTION

Collagen and keratin are important structural proteins.

Protein functions

Transport and storage; hemoglobin transports oxygen in the blood and ferritin stores iron in the liver.

Enzymes catalyze most biochemical reactions. Binding of substrate depends on specific noncovalent interactions.

Membrane receptor proteins signal to the cell interior when a ligand binds.

Actin and myosin form contractile muscle fibers.

Casein and ovalbumin are nutritional proteins providing amino acids for growth.

The immune system depends on antibody proteins to combat infection.

Regulatory proteins such as transcription factors bind to and modulate the functions of other molecules, for example DNA.

Basic Concepts in Genetics

Cells are of two basic types: eukaryotic and prokaryotic A gene is the fundamental unit of heredity Genes come in multiple forms called alleles Genes encode phenotypes Genetic information is carried in DNA and RNA Genes are located on chromosomes Chromosomes separate through the processes of mitosis

and meiosis Genetic information is transferred from DNA to RNA to

protein Mutations are permanent, heritable changes in genetic

information Some traits are affected by multiple factors Evolution is genetic change