DNA and Genes

The cell is the fundamental structural and functional unit of all living organisms. There are certain differences between the cells of different living beings as well as the cells in the different part of the living organism. All cells contain a fluid called cytoplasm and a nucleus, and are enclosed in a cell membrane. Operations within the cells and the coordination among various cells make the being live. The life of all the living beings is, therefore, based upon the working of the cells.

The nucleus of a cell contains a chemical DNA (deoxyribonucleic acid). All the instructions needed to direct the activities of cell are contained within the DNA. DNA is a polymer The monomer units of DNA are nucleotides, and the polymer is known as a “Polynucleotide.” There are four different types of nucleotides found in DNA, differencing only in he nitrogenous base. The four nucleotides are adermine (A), guanine (G) cytosine (C) and thymine (T). DNA from all organisms is made up of the same chemical and physical components. The DNA sequence is the particular side-by-side arrangement of bases along the DNA strand (e.g. ATTCCGGA). This order spells out the exact instructions required to create a particular organism with its own unique traits. The DNA is normally in the form of a double strand (double helix) where the second strand is complementary to the first strand. That is, in the second strand a sequence such as AGCTTT is replaced by TCGAAA which carries the same information.

The genome is an organism’s complete set of DNA. Genomes vary widely in size: the smallest known genome for a free-living organism (a bacterium) contains about 600000 DNA base pairs, while human and mouse genomes have some 3 billion. Except for mature red blood cells, all human cells contain a complete genome.

DNA in the human genome is arranged into 24 distinct chromosomes, physically separate molecules that range in length from about 50 million to 250 million base pairs. Each chromosome contains many genes, the basic physical and functional units of heredity. Gregory Mendel was the first to realize through extensive experiments with breading of peas that at the lowest level, inheritance is binary, and that there is a minimum unit of inheritance now known as a “gene”. Genes are specific sequences of bases that encode instructions on how to make proteins. Genes comprise only about 2% of the human genome, the remainder consists of non coding regions, whose functions may include providing chromosomal structural integrity and regulating where, when and in what quantity proteins are made. The human genome is estimated to contain about 30000 genes.

Gregory Mendel showed that the characteristics of parents are passed on to their offspring through genes These genes might produce visible characteristics in offspring, or might be carried for possible transmission to another generation. The children of one set of parents do not inherit all the same characteristics.

The union of two cells, the egg from the mother and the sperm from the father is the beginning, of new individual. These two cells like all other carry within them material that forms a definite number of chromosomes. These chromosomes carry heredity factors or genes. Chromosomes are pairs and each chromosome contain 1000 or so genes that also occur in pairs.

The process of inheritance is based upon the process in which the offspring receives one of each gene pair from each parent. Some genes are dominant and some are recessive. An individual with dominant gene, for a particular characteristic, displays that characteristic whether only one or both genes in the pair are dominant. If a gene is recessive, however, the characteristic associated with it does not show up unless both genes in the gene pair are recessive. In case only one gene in a pair is recessive, its effect will be marked by its dominant partner, but the recessive gene may still be passed on to the individual’s offspring. Some characteristics are produced by a single gene or gene pair. Whereas multiple – factor inheritance involves the action of several genes.

Genes are now known to be implemented as sequences of genetic code that direct specific cells to produce a particular protein at a particular time. An essentially infinite number of possible different protein molecules can be produced depending on the particular order of amino acid molecules used in their construction. The code for protein production has been “broken” so that we now know that a three-letter sequence (a codon) is used to specify a particular amino acid (there are 20 amino acids) For instance, the sequence GGC specifies that the amino acid glycine is to be added to a protein molecule. Start and stop codons mark the beginning and end of a protein coding sequence in a manner startlingly like modern data communications schemes There are 64 possible codons and only 20 possible amino acids so some redundancy and error correction exists. The regulatory code sequences in genes that specify in which parts of the body and/or at which times a protein will be produced are much more complex and less well understood.

The genetic code has been compared to a blueprint specifying the design of an organism. In fact the genetic code specifies not only the design of the organism but provides for the mechanisms needed to “read” the code and manufacture the components of the organism as well as specifying the procedures needed for the life processes of the finished organism. Simple organisms are completely defined genetically. Each tiny nematode worm has exactly 958 cells. Humans, on the other hand, have trillions of cells and 30,000 genes so the genetic code is more of a general plan. For example, major blood vessels are genetically specified. Everybody has an aorta. But minor blood vessels grow where needed according to genetically defined rules.

Although all the somatic cells in an organism contain the complete code, in any given cell only a relatively few genes are active. The difference in the genes that are active determines the difference between, say, liver and brain cells. A complex gene logic determines when and where a particular gene will be “turned on”. The gene logic can accommodate varying amounts of positional detail. The gene logic also controls when various activities will take place. Cells divide rapidly in growing organisms but do not divide in adults unless needed to replace dead or discarded cells. (Cancer involves a major breakdown in the gene logic in which cells grow in both an inappropriate position and at an inappropriate time. Cancer is thought to require multiple mutations, some of which can be inherited.)

The early insight from Human DNA sequence is summarized below:-

  1. Human genome contains 3 billion bases.
  2. An average gene consists of 3000 bases.
  3. The functions are unknown for more than 50% of discovered genes.
  4. The human genome sequence is almost (99.9%) exactly the same in all people.
  5. About 2% of the genome encodes instructions for the synthesis of proteins.
  6. Repeat sequences that do not code for proteins make up at least 50% of the human genome.
  7. Repeat sequences are thought to have no direct functions. But they shed light on chromosome structure and dynamics. Over time more repeats reshape the genome by rearranging it, thereby creating entirely new genes or modifying and reshuffling existing genes.
  8. The human genome has a much greater portion (50%) of repeat sequences than the mustard weed (11%), the worm (7%) and the fly (3%).
  9. Over 40% of the predicted human proteins share similarly with fruit-fly or worm proteins.
  10. Genes appear to be concentrated in random areas along the genome, with vast expenses of non coding DNA between.
  11. Chromosome 1 (The largest human chromosome) has the most genes (2968), and the Y chromosome has the fewest (231).
  12. Genes have been pinpointed and particular sequences in those genes associated with numerous diseases and disorders including breast cancer, muscle disease, deafness and blindness.
  13. Scientists have identified about 3 million locations where single base DNA differences occur in humans. This information promises to revolutionize the processes of finding DNA sequences associated with such common disease as cardiovascular diseases, diabetes, arthritis, and cancers.

Scientists suggest that the genetic key to human complexity lies not in a gene number but in how gene parts are used to build different products in a process called alternative splicing. Other underlying reasons for greater complexity are the thousands of chemical modifications made to proteins and the repertoire of regulatory mechanisms controlling these process.

The HGP project is complete, many questions still remain unanswered, including the function of most of the estimated 30000 genes. Researches also do not know the role of Single Nucleotide Polymorphisms (SNPs), single DNA base changes within the genome or the role of non-coding regions and repeats in the genome.

Mice and humans (indeed, most or all mammals including dogs,

Table 2: Comparative genome sizes of humans and other organisms.

cats, rabbits, monkeys and apes) have roughly the same number of nucleotides in their genomes – about 3 billion base pairs. This implies that all mammals contain more or less the same number of genes.

Gene duplication occurs frequently in complex genomes; sometimes the duplicated copies degenerate to the points where they no longer are capable of encoding a protein. However, many duplicated genes remain active and over time may change enough to perform a new function. Since gene duplication is ongoing process, mice may have active duplicates that humans do not posses, and vice versa. These appear to make up a small percentage of the total genes, not larger than 1% of the total. Nevertheless, these novel genes may play an important role in determining species specific traits and functions.

What really matters is that subtle changes accumulated in each of the approximately 30000 genes add together to make quite different organisms. Further, genes and proteins interact in complex ways that multiply the functions of each. In addition, a gene can produce more than one protein product through alternative splicing or post-translational modification; these events do not always occurs in an identical way in the two species. A gene can produce more or less proteins in different cells at various times in response to developmental or environmental cues, and many proteins can express disparate functions in various biological contexts. Thus subtle distinctions are multiplied by the more than 30000 estimated genes.

Some nucleotide changes are neutral and do not-yield a significantly altered protein. Others, but only a relatively small percentage, would introduce changes that could substantially alter what the protein does. Put these alterations in the context of known inherited diseases, a single nucleotide change can lead to inheritance of sickle cell disease, cystic fibrosis or breast cancer. A single nucleotide difference can alter protein function in such a way that it causes a terrible tissue malfunction. Single nucleotide changes have been linked to hereditary differences in height, brain development, facial structure, pigmentation and many other striking morphological differences ; due to single nucleotide changes, hands can develop structure that look like toes instead to fingers, and a mouse’s tail can disappear completely. Many of the average 15% nucleotide changes that distinguish humans and mouse genes are neutral, some lead to subtle changes, where as others are associated with dramatic differences. Add them all together, and they can make quite an impact, as evidenced by the huge range of metabolic, morphological, and behavioral differences we sea among organisms.

Although genes get a lot of attention, it is the proteins that perform most life functions and even make up the majority of cellular structures. Proteins are large, complex molecules made up of smaller subunits called amino acids. Chemical properties that distinguish the 20 different amino acids cause the protein chain to fold up into specific three dimensional structures that define their particular functions in the cell.

The constellation of all proteins in a cell is called its proteome. Unlike the relatively unchanging genome, the dynamic proteome changes from minute to minute in response to tens of thousands of intra-and-extra cellular environmental signals. A protein’s chemistry and behaviour are specified by the gene sequence and by the number and identities of other proteins made in the same cell at the same time and with which it associates and reacts. Studies to explore protein structure and activities, known as proteomics, will be the focus of much research for decades to come and will help elucidate the molecular basis of health and disease.

Most genes contain a switch called promoter. This switch regulates the activities of the gene and decides when and how the gene should become or not become active. An enhancer also works in the gene. The promoter and enhancer work only when the transcription factors responsible for mutation are operating. The genes are our active partners and are sensitive to the changes taking place in our body and mind and they register these changes by making suitable changes in their structure. By channeling our thoughts in a specific direction the genes can be changed, thus enabling us to progress in a desired way. This supports the view that spiritual persons can increase their power by sacred thoughts and determination. The genes are not our masters but are our servants, they are governed by our thoughts and influenced by our environment.

Studies in behavioral genetics have shown that both genetic and environmental factors influence the normal and deviant behavior of human beings. Only a few decades ago, psychologists believed that characteristics of human behavior were almost entirely the result of environmental influences. These characteristics now are known to be genetically influenced, in many cases to a substantial degree. Intelligence and memory, novelty seeking and activity level, and shyness and sociability all show some degree of genetic influence.

The principal role of genes in the chromosomes of human has now been identified. Faulty genes in chromosomes lead to different diseases as mentioned below.

  • CH1: Contains records of past lives. Faulty gene for GBA enzyme, which breaks down certain fats, leads to Gaucher’s, disease.
  • CH2: It contains the history of journey leading to human life.
  • It has details of births in various species we lived before. Faulty PAX – 3 gene is associated with deafness and color difference in eyes. This causes Wardenburg syndrome.
  • CH3: Contains evidences for the entire past history in the form of genes. Faulty VHL gene causes abnormal blood vessel formation. This gives von Hippel – Lindau disease. The genes are related to diabetes, obesity, etc.
  • CH4: This contains information about our future. It also carries hints about forthcoming disease and traits. Faulty gene causes dementia. This leads to Huntington’s disease.
  • CH5: This is very sensitive to environment and contains information about our immune system. It helps in study of genetic disease like asthma, diabetes, etc. Faulty gene cause malformed hands and feat. This leads to diastrophic dysplasia.
  • CH6: This is the intelligent chromosome, it is the basis of our intelligence. It has been shown that in some cases intelligence is hereditary. Faulty SCA1 gene causes clumsiness through withering of the cerebellum. This leads to Spino-cerebellaratrophy.
  • CH7: It contains those characteristics which determine our behavior as human being. This is regarded as the most important chromosome. Faulty gene causes fatal build-up of mucus in lungs and pancreas. This leads to Cystic fibrosis. Chromosome-7 contains genes related to William Neuron Syndrome which causes mental disability and defiguring of face. They also influence leukemia, the cancer of blood cells.
  • CH8: This contains information about our likings and choices. Our habits and nature are stored and transmitted to next life. This means that our merits and demerits are also influenced by hereditary factors. Defective gene causes premature ageing. This leads to Werner’s syndrome.
  • CH9: This determines the blood group. It also has a role in disease we suffer. Skin cancer is more likely in people with faulty CDKN2 tumor repressor gene. This leads to Malignant melanoma
  • CH 10: This chromosome contains the gene CYP17, which produces an enzyme that converts cholesterol into harmones called cartisol and Testosterone. These hormones produce stress in the body. Defect in MEN2A gene causes tumors of thyroid and adrenal glands. This leads to multiple Endocrine Neoplasia.
  • CH11: This contains genes which influence our personality. Harvey RAS oncogene predisposes to common cancers. This leads to cancer.
  • CH12: This is self assembled. Defects in PAH gene causes mental retardation by blocking dygestion of common amino acid in food. This leads to Phenylketonuria
  • CH13: Stores characteristics of the past lives. Defects in BRCA 2 gene raises risk of breast cancer.
  • CH14: This is of indestructible nature. Faulty AD 3 gene is linked with the development of plaques in the brain. This leads to Alzheimer’s disease.
  • CH 15: Determines gender. Abnormal FBN1, gene weakenes connective tissue potentially rupturing blood vessels. This leads to Marfan’s syndrome (position unknown).
  • CH16: This contains memory. Faulty PKD1 gene causes cysts to form, which trigger kidney failure. This leads to polycystic kidney disease.
  • CH17: This determines the life span. Mutations in P53 gene increase vulnerability to cancer. BRCA1 predisposes to breast cancer.
  • CH18: Helps in recovery from illness. Damage to DPC4 gene accelerates pancreatic cancer
  • CH19: This determines fertility. Defective gene for apolipoprotein raises blood cholesterol, predisposing to artery blockage. This leads to coronary heart disease.
  • CH20: Abnormal adenosine deaminase (ADA) gene destroys immunity. Correctable by gene therapy. This leads to severe combined immunodeficiency.
  • CH21: Wasting disease linked with defective superoxide dismutase I (SODI) gene. This leads to Lou Gehrig’s disease.
  • CH22: This charactrizes freedom of thought. Abnormal DGS gene triggers heart defects and facial changes. This leads to DiGeorge syndrome. Chromosome-22 plays an important role in immune system, mental disturbances and some types of cancers.
  • CH23: Abnormal DMD gene triggers muscle degeneration. This leads to Duchenne muscular Dystrophy.
  • CH24: Governed by the gene for testis – determining factor. This leads to Testicle development.