1Genetic VariationPopulations exposed to selection often evolve rapidly. Alleles that confer increased survival and reproductive ability in the new conditions rapidly increase in frequency while alleles that wereconditions rapidly increase in frequency, while alleles that were common decrease in frequency.How does the genetic variation arise?One of the central tenets of the modern model of evolution is that variation does not arise in response to need. Instead, genetic variation is present in natural populations before it is exposed to 1ppp pselection, in the form of rare alleles. New sources of selection results in an increase in allele frequencies that confer high fitness.An alternative view is that new alleles that confer high fitness arise in response to exposure to selection. This is the “Neo-Lamarckian” view.Two different experiments with bacteria originally provided evidence that variation does not arise in response to need. Luria and Delbruck looked at variation among bacteria for resistance to a phage. They reasoned that if variation arises in response to need, the incidence of new resistance in cultures of originally nonresistant bacteria should not vary greatly among independent cultures.should not vary greatly among independent cultures.They started multiple cultures of nonresistant bacteria, allowed them to multiply, and then exposed the bacteria to phage to test for resistance. Under the hypothesis that variation arises in response to need, they would expect all variation to arise after exposure. As a result they’d expect little variation in the number of resistant colonies among cultures. Their expectation:22Under the hypothesis that variation arises randomly, not in response to need, resistance could appear in any generation, and thus some cultures would have many resistant bacteria (as a result of early mutation) and some cultures would have none (as result of no mutation). They expected great variation in the number of )ypgresistant colonies among cultures:3This is what Luria and Delbruck found.In the second experiment, Joshua and Esther Lederberg used replica plating to determine if penicillin resistance in bacterial colonies was present before exposure to penicillin or only arose after exposure to penicillin. They cultured nonresistant bacteria and then exposed them to penicillin. Their technique allowed them to determine if the original colonies from which the resistant bacteria were derived were resistant before exposure to penicillin.Their results showed that resistance did not arise during exposure t i illi4to penicillin. Resistance arose in the culture before exposure to penicillin.3Mutation - the alteration of a region of DNA or chromosome; and altered state of a region of DNA or chromosomeTypes of mutations:base pair substitution-a single base pair change in DNA alsobase pair substitutiona single base pair change in DNA, also called a point mutationPoint mutations can result in single amino acid changes (nonsynonymous5(nonsynonymous mutation) or no change in amino acid –(synonymous mutation)Nonsynonymous mutations may have small or large effects on the properties of the protein product of the gene.A single base pair addition or deletion is a frameshift mutation -the result is a change in reading frame of RNA product of the gene and many amino acid changes in the protein product-usuallyand many amino acid changes in the protein product usually results in a nonfunctional protein product.64Intragenic recombination Original Sequence: ATTGATCGATCTATGCTAACTAGCTAGATACGRecombination can also result in sequence changesMutation Sequence 1: ATGGATCGATCTATGCTACCTAGCTAGATACGMutation Sequence 2: ATTGATCGATGGATGCTAACTAGCTACCTACGRecombination ATGGATCGATGGATGC7Sequence TACCTAGCTACCTACGThe amino acid changes resulting from the original two point mutations are combined in a single protein as a result of recombination.Unequal crossing-over results in sequence duplications and deletions.Unequal crossing-over usually occurs in regions where there are tandem repeats. The result can be a reduction in the number of repeats or an increase in the number of repeats.8High numbers of tandem repeats make a region liable to unequal crossing-over and additional duplications. It can give rise to gene families (multiple copies of variants of a single gene) and new functional genes.5Transposable elements - sequences of DNA that can be inserted into regions of the genome Insertion of a sequence of bases into a functional gene or the regulatory region of a functional gene can destroy normal functioning of that gene. Transposable elements can result in the movement of neighboring genes that were not initially part of the transposable elements.Recombination between transposable elements9transposable elements can result in deletions or inversions of base pair sequences.Examples of mutations:Sickle-cell anemia - a single base pair substitution that results in a single amino acid change in the β chain of HbPrecocious puberty - a single amino acid change in the gene for the receptor for luteinizing hormone results in males that show signs of puberty as early as age 4.Cystic fibrosis - a fatal disease that occurs in 1 in every 2500 births among northern Europeans is due to a mutation in a chloride ion channel protein. Different mutations account for the same condition: a deletion of 3 base pairs results in the deletion of a single amino 10pgacid, a conversion of an arginine codon into a stop codon, an alteration in a splicing enzyme has resulted in the deletion of an exon from the mRNA transcribed from the gene.Retinitis pigmentosa - a degenerative disease of the retina - can be caused by mutations in at least 8 different genes.6Hemophilia - caused by mutations in two different genes for blood clotting proteins. The mutations can be base pair substitutions, small deletions, small duplications. Twenty percent of the cases of hemophilia A are caused by an inversion of a long sequence of bases within one of the genes.Huntington’s disease - a fatal neurological disorder - is due to an excessive number of repeats of the sequence CAG - normal forms of the genes have 10 to 30 repeats, mutants have more than 75Although most mutations are have deleterious effects on the11Although most mutations are have deleterious effects on the encoded protein some have beneficial effects and have been important in evolutionFOXP2 - encodes a transcription factor -