Genetics: From genes to genomes - Chapter 20: Beyond the individual gene and genome

PowerPoint to accompanyGenetics: From Genes to GenomesFourth EditionLeland H. Hartwell, Leroy Hood, Michael L. Goldberg, Ann E. Reynolds, and Lee M. SilverPrepared by Mary A. BedellUniversity of Georgia*Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th editionBeyond the Individual Gene and Genome*PART VICopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20Evolution at the Molecular Level20.1 The Origin of Life on Earth20.2 The Evolution of Genomes20.3 The Organization of Genomes20.4 A Comprehensive Example: Rapid Evolution in the Immune Response and in HIVCHAPTER OUTLINECHAPTERCharles Darwin's theory of evolution"On the Origin of Species by Means of Natural Selection"Published in 1859, based on 5 years of collecting specimens from around the globeThree principles:Variation exists among individuals of a populationVariant forms of traits can be inheritedSome variant traits confer an increased chance of surviving and reproducingCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*The origin of life on earthSelf-replicating molecules may have led to the complexity of cellsThe first step in life had to fulfill three requirements:Encode information by variation of letters in strings of a simple digital alphabetFold in three dimensions to create molecules capable of self-replication and other functionsExpand the population of successful molecules through selective self-replicationCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*The RNA world1980s, Thomas Cech discovered ribozymes - RNA that can catalyze chemical reactionsCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Fig 20.1RNA satisfies all three requirements of the first replicator: linear strings encode information, folds into a 3-dimensional molecular machine, reproduces itselfIntrinsic disadvantages of RNARelatively unstableLimited capability for 3-dimensional folding compared to proteinsNo record of intermediates between an RNA world and cell complexitiesEvolution of living organisms4.5 billion yrs ago − coalescence of planet earth4.2 billion yrs ago − emergence of informational RNA3.7 billion yrs ago − life began3.5 billion yrs ago − oldest fossilized cells (see Fig 20.2)1.4 billion yrs ago − emergence of eukaryotesSymbiotic incorporation of single-celled organisms into other single-celled organismsComplex compartmentalization of cell interior (nucleus)1 billion yrs ago − ancestors of plants and animals diverged0.57 billion yrs ago − explosive appearance of multicellular animals (metazoans) and plantsCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Living organisms evolved into three kingdomsCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Fig 20.3The length of the branches is proportional to the times of species divergenceThe Burgess shale of southeastern British ColumbiaOne of the most amazing finds in paleontology!Enormous diversity in body plans – many are extinct but some still existPunctuated evolution – short periods of explosive changeAll basic body plans of metazoans are representedCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Fig 20.4The evolution of humans35 million yrs ago − humans arose from a common ancestor to most contemporary primates6 million yrs ago – divergence of humans and chimpanzees from a common ancestorCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Fig 20.5Similarities between chimps and humansGenomes are 99% similarKaryotypes are nearly the same (see Fig 12.11)No significant differences in gene functionDifferences between species may have been caused by only a few thousand isolated genetic changesSpecies-specific differences probably occurred because of alterations in regulatory sequencesCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*DNA alterations form the basis of genomic evolutionNew mutations provide a continuous source of variationReplacement of individual nucleotides in coding regions:Synonymous – substitutions have no effect on encoded amino acidNonsynonymous – substitutions cause change in amino acid or premature termination codonOrder and types of transcription factor binding sites in gene promoters can be alteredMutations can be deleterious, neutral, or favorableCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Classification of mutations according to effectNeutral mutations are not affected by the agents of selectionSurvive or disappear from a population by genetic driftSynonymous mutations can produce minute advantage or disadvantageAvailability of different tRNAs and tRNA-synthetases?Deletions and insertions almost certainly have an effectMutations with only deleterious effects disappear because of negative selectionMutations with advantageous effects will increase in the population because of positive selectionMay become fixed in the populationCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Gene regulatory networks may dominate developmental evolutionSea urchins and sea stars diverged ~ 500 million yrs agoBut, they share some basic gene networks (Fig 20.6b)Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Fig 20.6aGene regulatory networks in sea urchins and in sea starsCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Rewiring of a gene regulatory network can encode enormous phenotype changeFig 20.6bAn increase in genome size generally correlates with evolution of complexityDuplication and diversification of genomic regionsCan occur at random throughout genomeSizes range from a few nucleotides to the entire genomeCan occur through transposition or unequal crossing-overEither the original or copy of the gene can accumulate mutationsAcquisition of repetitive sequences – can make up more than 50% of a genome Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Transposition may occur through excising and reinserting the DNA segmentCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Fig 20.7aTransposition events that produce duplicationsTransposition through an RNA intermediateCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Transposition through a DNA intermediateFig 20.7bFig 20.7cTransposition through direct movement of a DNA sequenceAfter transposition occurs in a germ cell, the new copy of the transposon may become fixed in the next generationCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Fig 20.8Duplications resulting from unequal crossing- overAlso referred to as "illegitimate recombination"Mediated by sequence similarity between related sequences located close to each otherAfter the initial duplication, subsequent rounds of unequal crossing over can occur readilyCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Fig 20.9Duplicated genes can evolve into pseudogenes or evolve new functionsPseudogenes – nonfunctional genes that results from random mutations in a duplicated geneLoss of regulatory function, substitutions at critical amino acids, premature termination, frame-shift mutation, altered splicing patternsAccumulate mutations at a fast paceNew functions can arise in a duplicated geneRandom mutations provide selective advantage to the organismThe new gene usually has a novel pattern of expressionCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Evolutionary histories are diagrammed in phylogenetic treesCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Fig 20.10Molecular clock – provides a good estimate of time of divergence because rate of evolution is constant across all lineagesPhylogenetic tree illustrates relatedness of homologous gene or proteinsNodes are taxonomic unitsBranch lengths represent time that has elapsedFour levels of gene duplication have fueled evolution of complex genomesAt each level, diversification and selection can occur Exons duplicate or shuffleEntire genes duplicate to create multigene familiesMultigene families duplicate to produce gene superfamiliesEntire genome duplicates to double the number of copies of every gene and gene familiesCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Duplications create multigene families and gene superfamiliesHierarchical generation of greater amounts of new information at each levelCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Fig 20.11The basic structure of a geneCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Fig 20.12Domains in antibody proteinsDiscrete exons can encode the structural and functional domains of a proteinDuplication of exons, can create tandem functional domains Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Fig 20.13The tissue plasminogen activator gene evolved from shuffling of three genesNew proteins with different combinations of functions can be created by exon shufflingCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Fig 20.14Duplications of entire gene can create multigene familiesMultigene family – set of genes descended by duplication and diversification from one ancestral geneCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Fig 20.15Unequal crossing over can expand and contract gene numbers in multigene familiesCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Fig 20.16Intergenic gene conversion can increase variation in members of a multigene familyAlternative outcome to unequal crossing-overAllows transfer of information from one gene to anotherCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Fig 20.17Increasing the number of alleles through gene conversionMajor histocompatibility complex (MHC) of mice – a pseudogene family was the reservoir of genetic information to produce a dramatic increase in variationCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Fig 20.18Concerted evolution can lead to gene homogeneityCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Fig 20.19Evolution of gene superfamilies Gene superfamily – large set of related genes that is divisible into smaller familiesGenes in each family are more closely related to each other than to other members of the superfamilyRepeated gene duplication events followed by divergenceGlobin gene superfamily – three branches in all vertebratesTwo multigene families (β-like genes and α-like genes) and a single myoglobin geneHox gene superfamily – four branches in mice, only one in Drosophila Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Evolution of the mouse globin superfamilyCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Fig 20.20Evolution of the Hox gene superfamily of mouse and DrosophilaCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Fig 20.21Repetitive “nonfunctional” DNA families constitute nearly one-half of the genomeMany repetitive nonfunctional DNA families consist of retroviral elements that have integrated into the hostProvirus can be active or inactiveLong INterspersed Elements – LINE family"Selfish DNA", encodes reverse transcriptaseVery old family, exists in many organismsMay have been source material for retrovirusesShort INterspersed Elements – SINE family (e.g. Alu element in humans)Does not encode reverse transcriptaseEvolved from small cellular RNAs Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Creation of a LINE gene familyCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Fig 20.22Creation of a SINE gene familySINEs depend on availability of reverse transcriptase encoded by other elements (LINEs or retroviruses)Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Fig 20.23The potential selective advantage of selfish elementsSINEs and LINEs have had profound impacts on whole-genome evolutionCatalyze unequal homologous crossover eventsThese duplication events can initiate formation of multigene familiesSome evolved regulatory functions – can act as enhancers or promotersCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Simple sequence repeats (SSRs)Tandem, nonfunctional repeats scattered throughout mammalian genomesVary in size of repeating units (2 – 100s of nucleotides)Microsatellites, minisatellites, and macrosatellitesVery useful molecular markers for genome analysis and genotyping (Chapter 11)Highly susceptible to unequal crossing-over and are highly polymorphic in size Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Centromeres and telomeres contain many repeat sequencesCentromeres – tandem arrays of noncoding sequences that interact with mitotic and meiotic spindle fiberse.g. Human alphoid DNA – 171 bp repeat that extends > 1 Mb on either side of centromere in each chromosomeEach repeat is < 200 bp in lengthIncrease efficiency and/or accuracy of chromosome segregationTelomeres – tandem arrays of noncoding sequences that are at ends of all mammalian chromosomesArrays are 5 – 10 kb in lengthEach repeat is 6 bp in lengthEssential role in maintaining chromosome lengthCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*A comprehensive example: Rapid evolution in the immune response and in HIVEvolutionary battle at the molecular level between the AIDS virus and cells of the immune systemAfter viral infection, virus-specific immune response ensues that can destroy the pathogenHIV has a high mutation rate and is able to diversity and amplify itself via selectionSpeed of viral evolution is faster than the immune responseEffective triple-drug therapies act to reduce the rate of viral replicationCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*The immune responseDifferentiated B cells secrete antibodies that destroy or neutralize antigensExpanded numbers of memory T cells and B cells allow a rapid response to the 2nd encounter with an antigenCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 20*Fig 20.24