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Errors and Mutations
Errors in copying genetic data are the source of the genetic changes that drive evolution. Some errors, such as in a sequence which controls basic cell design or oxygen transport or other crucial process are almost always immediately fatal and so are immediately “selected out” and do not propagate into the genetic code of descendent organisms. This sort of sequence tends to be “well conserved” after billions of years. Humans share some sequences with yeast that both humans and yeast must have received from a common ancestor. Other sequences that control “how much” (how long a claw, how much fur, etc.) are the source of the variation that drives natural selection. An error in such a sequence could only cause slight variation of a parameter and only very mildly affect fitness. Finally, some sequences (as much as 90 percent of the human genome) have no apparent biological purpose. Changes in such a sequence generally have no effect on the organism and are not selected against at all, thus apparently freely propagating to future generations.
Genes
A gene is a hereditary unit that can be passed on unaltered for many generations. The gene pool is the set of all genes in a species or population. Evolution can occur without morphological change, which can occur without evolution. Humans are larger now than in the recent past, a result of better diet and medicine. Phenotypic changes like this induced solely by changes in environment do not count as evolution because they are not heritable; in other words the change is not passed on to the organism's offspring. Phenotype is the morphological, physiological, biochemical, behavioral and other properties exhibited by a living organism. An organism's phenotype is determined by its genes and its environment. Most changes due to environment are fairly subtle, for example size differences. Large scale phenotypic changes are obviously due to genetic changes and therefore are evolutionary. Genes perform the actual control of physiological functions. Each chromosome can have thousands of genes. The human genome contains approximately 30,000 genes but the actual number is still unknown. The structure of the sequence of information representing a gene as seen reading sequentially along a chromosome typically includes regulatory regions at the beginning or end of the gene sequence that determine when and where the gene is activated. Genes exert strong controls on life-span and patterns of ageing. Yet we know little of how humans live five times longer than cats, cats live five times longer than mice and mice live 25 times longer than fruit flies or why the onset of Alzheimer's disease (AD) often differs by many years in identical twins. Equally obscure is the role of genetics in the unprecedented increases of human life expectancy at advanced ages. To approach these puzzles we must understand how the potential life-span of an individual is determined by the interplay between gene and environment, which ultimately modulates the rates of molecular and cellular involution during ageing. Clearly, individual humans are subject to genetic risks for age related diseases, such as AD, cancer, diabetes, heart disease and stroke. Other mammals share subsets of these age-related diseases but we do not know causes of mortality in flies or worms. The incidence of diverse diseases accelerates exponentially with increasing age, it is difficult to critically resolve whether general age-related changes, such as the loss of skin elasticity and the slowing of reflexes are mediated by the mechanisms that govern specific age-related diseases. A gene is often thousands of bases in length. The coding region determines which protein will be produced by the gene, that is, the sequence of amino acid molecules which will be constructed to produce a particular protein molecule (often referred to as the gene product). The properties of a protein are determined not only by the number and type of the amino acid molecules used in its construction but also by the particular sequence in which the amino acids are assembled. The long protein molecules tend to “fold up” in very complex ways depending on the particular sequence. This folding and consequent shape of the molecule affects its properties. There are therefore an essentially infinite number of possible different proteins. The largest known human protein has 27,000 amino acids corresponding to 81,000 DNA nucleotides.
A particular three-letter sequence, ATG is the synchronization pattern denoting the start of a coding sequence; other three letter sequences (known in genetics parlance as codons) denote particular amino acids to be sequenced into a protein and the end of a coding sequence. Since there are 20 possible amino acids and 64 possible condons, some errors in the third symbol of a condon have no effect. For example, CTA, CTG, CTT and CTC all code for valine. This is a form of redundancy. The regulatory regions determine when, where and how much product will be produced. Some products are only produced in the liver some are produced only at certain times in an animal's life and so on. The regulation involves the detection of chemical signals which can either enhance or inhibit the gene's expression. Although some genes produce proteins used in the construction of tissue, many probably a majority products that act as signals to activate or inhibit other genes thus allowing the construction of a very complex regulatory logic framework. If the regulatory region determines that a gene is activated, the cell starts making copies of the genetic information in the coding region in the forms of small RNA molecules with sequences corresponding to the coding region. These messenger RNAs are used as templates by the cell machinery that produces the proper protein molecules. (Sometimes the RNA molecule itself is the gene product and performs some biological function such acting as a signal to other genes.) The genetic code snippets will preferentially adhere to a complementary string of code. “Gene chips” carrying hundreds of samples of potential snippet complements can be used to test for the presence of specific RNAs in a sample. Using such gene chips, researchers can detect the presence of various different RNAs in various tissues and thereby determine which genes were activated. In connection with anti-ageing research, detecting the differences in gene activity between a caloric restricted animal and not or between a progeria victim and not could produce valuable clues regarding ageing mechanisms. Coding regions in genes of more complex organisms have introns. Introns are portions of the coding regions that are spliced out and deleted from the code during the creation and processing of RNA. The deletion is caused by patterns at the beginning and end of the intron that match in a particular way. Since the introns are deleted, they have no known biological effect and are often considered “junk” DNA. The remaining (functional) portions of a coding region which are expressed in the RNA and subsequent protein are called exons. Exons are thought to represent only about one percent of human DNA. Introns in humans represent about five percent of DNA. Human genes have an average of five introns and a maximum of 178 introns. Genes are autonomous data units. They contain their own synchronization patterns and operate somewhat independently. Junk DNA can therefore exist between genes without disturbing their operation. The position (or locus) of a gene within a chromosome or on a particular chromosome generally does not appear to affect the functional operation of a gene. (In communications parlance such an autonomous unit would be referred to as a packet.) Some specific genes must be located on the sex chromosomes in order to accomplish sex differences between organisms.) If we inject a small loose string of DNA containing a single gene into a cell, the cell will happily produce the gene's protein product. This approach is used in some forms of gene therapy. However the loose strand of DNA would not be duplicated during cell division because such duplication requires the gene to be part of a chromosome. Methods for inserting new genes into chromosomes have been developed and are used in genetic engineering. Such a gene would be propagated during cell division and even possibly during reproduction of the organism. While junk DNA and gene location do not affect the functioning of genes they may well have significant evolutionary effects to be described. All normal humans are thought to have the same genes, specifying the same or nearly the same products, in the same order, on the same chromosomes. Genetic differences between humans are expressed in the exact digital content of their genes, generally minor differences such as single nucleotide substitutions. Mendelian genetics considers that some genes in a particular species can have two different specific contents or alleles such that two different results occur. Often one allele is represented by a gene that is disabled and therefore produces no functional product, while the other allele is represented by the functioning gene, a binary situation. In practice, some genes can have more than two alleles. A complex gene having tens of thousands of bases could possibly have many alleles. A single substitution difference in a coding region exon (for example an A could be replaced with a T) could cause a different protein or RNA product to be produced, which in turn could have a significant effect but could also have a mild or negligible effect. An error in the regulatory region or an error that deletes the start condon or adds a stop condon could cause the gene to become disabled and produce no useful product. Other errors could have more minor effects such as changing the amount of product produced. Many of the more than 1000 known human genetic diseases as well as most of the normal variations between individuals are caused by such single letter differences in the genome. In many cases of genetic disease, if one parent's gene is disabled, the other parent's corresponding gene provides enough products so that significant symptoms are avoided. The child and the first parent are carriers. If the genes received from both parents are defective, then the child has the recessive genetic disease. If one gene does not provide enough products to avoid symptoms or if an incorrect and deleterious product is produces then a defect in either parent's gene can cause disease symptoms in a dominant genetic disease or other trait. Many human genes appear to be duplicated another form of redundancy. So, by far the most likely possibility in a mutation is a single letter error. It would appear to be ridiculously unlikely that an entire functioning gene could be produced by a random mutation. The significance of this is covered in the section on ageing genes. Since the sequence of the human genome has been completed, it might seem a simple matter to have a computer program search through the genome and identify genes by their characteristic data patterns such as start and stop condons, regulatory sequences and intron patterns. In practice, although the start and stop codes are definite, the patterns involved in regulatory sequences and the patterns that denote the borders of an intron are often quite vague in that many different patterns appear to accomplish the same result. In adition, the genome contains pseudo gene patterns that resemble genes but are not functional. A pattern can be “definitively” considered a gene if a gene with the similar or same exons has been found in another species or if a genetic disease or other trait has been traced to two different forms of the (otherwise) same pattern. Due to these difficulties we do not yet know for certain even how many genes are in the human genome and have “definitively” identified relatively few genes.
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