Because of the many introns in mammalian genes, a single gene is often more than than 10,000 nucleotides long, and genes that span 100,000 nucleotides are not uncommon (Table 2-1). Figure 2-1. Two ways of representing the DNA double helix. Diagrams are of a very short section of the DNA molecule in each chromosome.
The complete nucleotide sequences of the genomes of the several organisms of major experimental interest will provide a critical reference data base for interpreting and studying the many human genes that will be discovered. To take just one example, an individual cancer researcher who discovers a new oncogene in a human tumor will have immediate access by computer search to all the proteins that are likely to have a related function in lower organisms. Since these genes can be experimentally manipulated in ways that are impossible in humans, the function of the corresponding gene can be determined much more readily in a fruit fly, a nematode worm, or a yeast cell. The results are certain to provide important insights into human cancer that could not be obtained by direct research on humans. Conversely, researchers interested primarily in yeast cells will benefit from the information about yeast genes that can be derived from studies on its homologues that are initially conducted with another organism.
The generation of a physical map of the human genome and the determination of its nucleotide sequence will provide an important research tool for basic biology. This is especially true because we expect a human genome project to support mapping and sequencing investigations that are carried out concurrently in other extensively studied organisms, including the Escherichia colibacterium, the lower eukaryote Saccharomyces cerevisiae(a yeast), the nematode worm Caenorhabditis elegans, the fruit fly Drosophila melanogaster, the mouse Mus musculus, and possibly also a plant such as maize or Arabidopsis. Analyzing these genomes will approximately double the total amount of DNA to be mapped and sequenced. But the additional effort will make it possible to test the function of genes that have been identified in humans in other organisms that are experimentally accessible and for which powerful genetic techniques exist. It will thereby be possible to firmly establish the exact role of these genes in important biological processes. Conversely, proteins that are discovered to be of special interest in any of these other organisms can be immediately identified by amino acid homology in the human, thereby enabling investigators to conduct well-focused studies of the function of the corresponding human protein and its gene. The extensive DNA sequence and functional comparisons that are generated will also represent an invaluable resource for evolutionary biologists. These and other implications for basic biology are discussed in greater detail in Chapter 3.
Even the complete sequence of DNA in the human genome will not by itself explain human biology. It will, however, serve as a great resource, an essential data bank, facilitating future research in mammalian biology and medicine. Humans, like all living organisms, are composed largely of proteins. For humans these are roughly estimated to be of 100,000 different kinds. In general, each gene codes for the production of a single protein, and a gene and its protein can be related to each other by means of the genetic code. Therefore, scientists will be able to turn to the DNA sequence of the human genome and obtain detailed information on both the structure and function of any gene or protein of interest. In addition, all genes and proteins will be classified into large family groups that provide valuable clues to their functions. In this way, many previously unknown human genes and proteins will become available for biochemical, physiological, and medical studies. The knowledge gained will have a major impact on health care and disease prevention; it will also raise challenging issues regarding rational, wise, and ethical uses of science and technology.
Each of our cells contains the same complement of DNA constituting the human genome (Figure 1-1.) The DNA sequence of every person's genome is the blueprint for his or her development from a single cell to a complex, integrated organism that is composed of more than 1013 (10 million million) cells. Encoded in the DNA sequence are fundamental determinants of those mental capacities—learning, language, memory—essential to human culture. Encoded there as well are the mutations and variations that cause or increase susceptibility to many diseases responsible for much human suffering. Unprecedented advances in molecular and cellular biology, in biochemistry, in genetics, and in structural biology—occurring at an accelerating rate over the past decade—define this as a unique and opportune moment in our history: For the first time we can envision obtaining easy access to the complete sequence of the 3 billion nucleotides in human DNA and deciphering much of the information contained therein. Converging developments in recombinant DNA technology and genetics make obtaining a complete ordered DNA clone collection indexed to the human genetic linkage map a realistic immediate goal. Even determination of the complete nucleotide sequence is attainable, although ambitious. The DNA in the human genome is remarkably stable, as it must be to provide a reliable blueprint for building a new organism. For this reason, obtaining complete genetic linkage and physical maps and deciphering the sequence will provide a permanent base of knowledge concerning all human beings—a base whose utility for all activities of biology and medicine will increase with future analysis, research, and experimentation.
Then the RNA can be translated into a protein molecule according to the genetic code (every group of three nucleotides codes for one amino acid). Nucleotide sequences adjacent to the coding sequences in each gene encode regulatory signals for activating or inactivating transcription of the gene. Geneactivity is a dynamic process; at any given time and in any given cell type, only a subset of genes is active. These active genes determine the course of embryological development and the characteristics of cells and organisms.
The human genome map and an ordered set of human DNA clones will be available as a resource for the use of all investigators, enabling them to concentrate on the most interesting parts of their research. In addition, new areas of research are likely to emerge as a result of this resource, particularly in relation to human health. In short, the committee believes that the mapping and sequencing project will make an important contribution to primary research conducted by small groups of independent investigators, extending their reach into currently inaccessible problems.
Sex cells, as opposed to body cells, contain only 23 chromosomes. Each parent gives their child 23 chromosomes, which means that the human body contains 46 chromosomes; therefore each of our body cells has two copies of a gene for each characteristic.
In most cases, you’ve got two copies of a gene – one from your mother and one from your father. The second word is phenotype. Phenotype is what you actually turn out to be, the way these genes get expressed. Biologists have a saying involving these two fancy words: “Genotype determines phenotype.”.
Biologists use two fancy words to describe the relationship between your genes and your physical traits. The first word is genotype. Your genotype is your genes for a given trait. In most cases, you’ve got two copies of a gene – one from your mother and one from your father.
Genetic composition determines much more than just the structure of a pea plant , or the colour of our eyes and hair, as it has a significant impact on the development of the entire body and it arranges our response to environmental stimuli. After a more detailed examination we find that we are in fact very different – some eat vast amounts of food and never gain weight, others are exceptionally talented in certain sports, while others still drink a cup of coffee and spend a sleepless night. These and many other individual traits are largely a consequence of the differences within the remaining 0.1% of our hereditary notation.
Mutation in Latin means change. When we refer to mutation in genetics, we mean the change in the DNA sequence. This can occur in various ways: a nucleotide can be inserted into a sequence, another can be erased, and another still can be replaced by another one. The replacement of one nucleotide by another, which is then inherited by the descendants and kept within the population, is called the SNP. SNPs can cause a protein, encoded by a gene, to change, which means that its function will be changed as well. And even though people are identical in more the 99% of their hereditary notation, the SNPs (and some rare DNA mistakes) make everyone unique.
Genes carry the information for the creation of protein. Protein is the foundation of the body. Also all the enzymes, the biological molecules which are the key to the proper operation of our organism are proteins by nature. Proteins are built from smaller molecules, named the amino acids.
Proteins are built from smaller molecules, named the amino acids. Genes actually carry the information which tells the amino acids how to create the corresponding sequence. The different amino acids in a specific sequence give rise to the corresponding protein.
Of the trillions of cells that compose our body, from neurons that relay signals throughout the brain to immune cells that help defend our bodies from constant external assault, almost every one contains the same 3 billion DNA base pairs that make up the human genome – the entirety of our genetic material. It is remarkable that each of the over 200 cell types in the body interprets this identical information very differently in order to perform the functions necessary to keep us alive. This demonstrates that we need to look beyond the sequence of DNA itself in order to understand how an organism and its cells function.
After the Human Genome Project, scientists found that there were around 20,000 genes within the genome, a number that some researchers had already predicted. Remarkably, these genes comprise only about 1-2% of the 3 billion base pairs of DNA []. This means that anywhere from 98-99% of our entire genome must be doing something other than coding for proteins – scientists call this non-coding DNA. Imagine being given multiple volumes of encyclopedias that contained a coherent sentence in English every 100 pages, where the rest of the space contained a smattering of uninterpretable random letters and characters. You would probably start to wonder why all those random letters and characters were there in the first place, which is the exact problem that has plagued scientists for decades.
A sequence of DNA is a string of these nucleic acids (also called “bases” or “base pairs”) that are chemically attached to each other, such as AGATTCAG, which is “read out” linearly. Experimental methods to determine the sequence of DNA, along with help from some powerful computers, ultimately gave scientists a sequence full of A’s, G’s, C’s, ...
Some scientists have voiced their concern that the money spent on this project (upwards of $200-300 million) could have been more useful in supplying individual researchers with grants. Some biologists have also voiced their concerns regarding how the results of the project were presented to the public, both in terms of the hype surrounding the project and the results themselves. Because of the expense and complexity of these types of studies, it is important for scientists to present an impartial perspective. The need for careful presentation to the public was demonstrated by the hype surrounding a recent paper published by NASA scientists on bacteria that could use arsenic in a way that had never been observed before. After announcing that they had discovered something new and exciting, even to the point of calling a press conference, the self-generated hype eventually imploded after the findings were ultimately refuted []. As with any new large-scale project, both scientists and the public must be patient in assigning value until the true benefits of the project can be realized.
The DNA that makes up all genomes is composed of four related chemicals called nucleic acids – adenine (A), guanine (G), cytosine (C), and thymine (T).
For instance, the genus Allium, which includes onions, shallots, and garlic, has genome sizes ranging anywhere from 10 to 20 billion base pairs.
It is remarkable that each of the over 200 cell types in the body interprets this identical information very differently in order to perform the functions necessary to keep us alive. This demonstrates that we need to look beyond the sequence of DNA itself in order to understand how an organism and its cells function.