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Chapter 12 Individual Genetic Variation and Gene Regulation Xodar Figure CO: Kittens © twobluedogs/ShutterStock, Inc. Overview • Natural selection acts on existing phenotypic variation • Mutations are necessary for evolution – multiple alleles, gene duplications, alterations in chromosome number, transposable elements, and modification of regulation all contribute to variation • Mutations – In Structural genes and Regulatory genes Variation: Central Questions • What is the relationship between the genetic variation of the genotype and variation of the phenotype? • genotype + gene regulation + gene interactions within the genome + developmental processes + environmental effects and constraints + randomvariation → phenotype Variation: Central Questions • What are the mechanisms by which mutations and modifications of gene regulation serve as sources of variation? Variation: Central Questions • What other sources of variation are available to populations? – Chapter 13: gene flow and random mutation • What are the ecological and developmental determinants of phenotypic variation? – Chapter 14: body size, geographic range, home range size, niche width, lifespan, environmental stress, population size and density, etc. Mutations Have Many Causes • Spontaneous Mutations – DNA copy errors • Induced Mutations – – – – Mutagens Radiation Viruses Transposons • Somatic Mutations • Germline Mutations Mutations and Health A Service of the U.S. National Library of Medicine POLYPOLOIDY (ENTIRE SETS OF CHROMOSOMES UK Science Museum Short Animation Mutations in the Genome • Point mutations can occur through: – substitutions (change in bases) including tautomer errors – insertions (introduction of bases) – deletions (loss of bases) within the DNA – or change in gene position: transpositions Mutations in the Genome • Major transposition of DNA segments can produce chromosomal inversions • Segments of DNA can be rearranged to new locations and even to other chromosomes producing chromosomal translocations Mutation From a Functional Perspective 1. Sense Mutation: There is a change in the DNA base sequence but no change in amino acids in the polypeptide structure 2. Missense Mutation: There is a change in the DNA base sequence, and a change in amino acids in the polypeptide structure, but the protein is still functional to some degree 3. Nonsense Mutation: There is a change in the DNA base sequence and a change in amino acids in the polypeptide structure, and the protein is non-functional, a fragment, or is not produced at all Transitions and Transversions Point Mutations Transitions outnumber Transversions 2:1 Tautomers of Nitrogenous Bases Point Mutations • Silent or synonymous – Silent mutations are much more likely when the point mutation is in the third position of the codon triplet Point Mutations • Replacement or nonsynonymous • Stop codon Pleiotropic Effects • Most genes have multiple or pleiotropic effects • A given mutation has the potential to have a wide variety of effects on reproductive fitness if the individuals carrying the mutant allele are exposed to a wide variety of environmental conditions or selection pressures • A given genotype may be adaptive in some environments, neutral in others, and maladaptive in still others Pleiotropic Effects Pleiotropic Effects: Inborn Errors of Metabolism Cystic fibrosis Sickle Cell Is a Point Mutation Sickle Cell is an Example of An Inborn Error of Metabolism For More on Sickle Cell From Harvard University Sickle Cell Disease a) Normal: DNA codes via mRNA for the amino acid, glutamic acid, one of many proteins in the hemoglobin molecule b) Sickle cell disease: A single base change in DNA codes via RNA for a different amino acid, valine • But this critical amino acid is important in proper folding of the hemoglobin molecule, which becomes defective, producing sickled red blood cells Sickle Cell Anemia widespread organ damage accumulates over time Figure 07: Sickle cell mutation Adapted from Strickberger, M. W. Genetics, Third edition. Macmillan, 1985. Sickle Cell and Natural Selection Heterozygote Superiority Due to an alteration in potassium transport in the red cells of individuals with some Hemoglobin S, i.e., both homozygous recessives and heterozygotes (carriers) for Hgb S, the malarial parasite cannot complete its life cycle easily inside these affected cells Loss-of-Function Mutations Insertion Deletion Stop Codon Frameshift mutations Transposons May Cause Frameshift Mutations • “Jumping Genes” direct the synthesis of additional copies of themselves, using transposase, which are introduced into neighboring regions of DNA which exhibit a particular target sequence Variation in Chromosome Number • Two major kinds of changes: – number of entire sets of chromosomes – numbers of single chromosomes within a set: aneuploidy • Repetitive doubling = polyploidy Polyploidy • Polyploidy occurs when there are more than two homologous sets of chromosomes • Most multicellular eukaryotic organisms are normally diploid • Polyploidy may occur due to abnormal cell division, i.e., nondisjunction events • Polyploidy occurs in some animals, such as goldfish, salmon, and salamanders, but is especially common among ferns and flowering plants, including both wild and cultivated species Polyploidy: Changes in Sets of Chromosomes Diploid cabbage species (Brassica oleracea - R and B. rapa - L) were crossed to produce the large, vigorous tetraploid species, Brassica napus. Failure of the spindle apparatus to separate chromosomes is a non-disjunction event Breeding an Artificial Tobacco Species in the Laboratory • Two diploid species, Nicotiana tabacum (2n = 48) and N. glutinosa (2n = 24) were crossed • The sterile triploid (2n = 36) could be propagated Figure 02: Flowers and vegetatively diploid gene numbers of the tobacco plants • An accidental chromosome doubling then yielded a fertile species, N. digluta, (2n = 72) The Evolution of Wheat • At least 30,000 years ago, in the Fertile Crescent of southwest Asia, a natural hybrid formed between two grasses, Triticum monococcum (wild einkorn) and a species of Aegilops (goat grass) Figure 01: Hybrid wheat © R0b/Dreamstime.com Triticum monococcum Aegilops The Evolution of Wheat • Later, tetraploid Triticum sps. hybridized with a diploid species to yield modern hexaploid wheat Fig. 1. Wheat spikes showing (A) brittle rachis, (B to D) nonbrittle rachis, (A and B) hulled grain, and (C and D) naked grain. J Dubcovsky, J Dvorak Science 2007;316:1862-1866 Published by AAAS Polyploidy • While rare, nondisjunction events do occur • Since plants often make large numbers of gametes, low probability events are more likely to occur • If a diploid pollen grain fertilizes a diploid egg, a tetraploid is born which is potentially reproductively isolated from the start • The incipient species can also reproduce vegetatively, avoiding the mechanical conflicts in meiosis until there are enough individuals to form a small interbreeding polyploid population The Polyploid Lifestyle • Polyploid plants are often large and hardy, even more vigorous and healthy than their diploid ancestors • They may be better competitors in the common environment and can increase their range at the expense of the parent species • The Polyploid Lifestyle • Sometimes, after generations, the tetraploid population, already reproductively isolated from its parent diploid population, accumulates enough genetic (and phenotypic) divergence to be recognized as a distinct species by scientists • In fact, it may have been a distinct biological species in terms of its own life history from the outset – in a single generation Triploidy • In other circumstances, a diploid gamete fertilizes a normal haploid gamete checkered whiptail lizard 3N • Then a triploid individual results 3N 3N • At meiosis, sets of 3 like chromosomes have great mechanical difficulty during the close alignment of synapsis Triploidy • Gametes are produced with chromosome numbers varying from the 1N haploid number to the 2N diploid number • Most of these gametes fail to produce viable offspring when they combine at fertilization, but sometimes those gametes that carry the 2N diploid number find and fertilize other like 2N diploid gametes and a tetraploid individual or population is produced after passing through this so-called triploid bottleneck Jefferson’s salamander grass carp The Polyploid Lifestyle • Self-fertilization is common in plants • Certain hermaphroditic animal species are capable of selffertilization • Animals may also become polyploid through parthenogenesis, which is reproduction by females without fertilization by males Parthenogenetic Species The Polyploid Lifestyle • Perhaps in later generations, some of these polyploid individuals achieve a return to sexual means of reproduction, but if not, asexual reproduction may be enough to permit the population to exist as a permanent community • Natural selection may even encourage the evolving population to return to sexual reproduction by favoring those individuals who can both self-fertilize and outcross, because those that can do both are more likely to leave more descendants in future generations Polyploidy • Modern molecular techniques (“clocks”) often allow estimates of times since divergence for polyploid series of related species cotton Shifts Between Sexual and Asexual Reproduction green peach aphid Myzus persicae Daphnia The Polyploid Lifestyle • The polyploids have the advantage of duplications at every locus • Therefore, all the old blueprints for useful proteins remain, while at the same time, another copy of all the genetic blueprints are available to accumulate mutations and develop novel proteins capable of performing new functions for the plant In this example, the spindle apparatus broke down, leaving a tetraploid cell that then divided normally thereafter The Polyploid Lifestyle • In contrast to polyploid plants, polyploid animals are often malformed and do not experience normal development • For example, it is well known from genetic studies, karyotype studies, of still born humans and from still born domestic animals, such as cows, horses, sheep, goats, cats and dog, that many of the naturally aborted fetuses were polyploids triploid fetus Human Triploids from Spontaneous Abortions Karyotype of 69,XXY (triploidy), common finding in spontaneous abortion. Risk for chromosomal anomaly in subsequent pregnancy is not increased significantly. syndactyly in triploid Similar karyotype of 69,XXX (triploidy) Animal Triploidy • Some scientists speculate that the reason animals do not tolerate polyploidy has to do with the regulation of growth of a specific body plan • In other words, an animal needs the right set of bones in the right place, the right set of neurons in the right place, the right set of muscles in the right place, and so on Severe intra-uterine growth retardation in maternal triploidy • The animal body plan is very complex and structural relationships must be matched precisely for the parts to work together effectively Human Triploids from Spontaneous Abortions • Some 1-2% of all human conceptions may be triploid, but most spontaneously abort • These may account for as many as 25% of chromosomally abnormal fetuses that spontaneously abort in the first trimester • The live birth rate is estimated at 1:2,500 • Triploidy is lethal – prenatally or early in the newborn period • However, rarely mosaicism occurs, and these individuals may live for a Triploidy - stillbirth at 39 weeks (69,XXX) while, but they are associated with - note the appearance of the hands profound mental retardation and other serious anatomical and physiological abnormalities A different specimen The Polyploid Lifestyle • Plants, on the other hand, have fewer parts, fewer organ systems, and can tolerate extremely divergent structural relationships • It is not crucial, for example, that plants be bilaterally or radially symmetrical The Polyploid Lifestyle • The rootlets, the stems, the leaves, and the flowers do not all have to appear at exactly the same places on the stems or branches of different individuals for these individuals to be viable, to be successful, and to be reproductively fit • This hypothesis is logical, but difficult to verify Chromosome Alterations • Potentially the largest phenomenon capable of contributing to the pool of mutations • Some chromosome changes affect only gene / locus order and organization • Others alter the amount of DNA available • Others alter blueprints, eliminate genes, or add copies of genes • Others influence linkage groups of genes Chromosome Rearrangements Occur During Meiosis Division I Synapsis Crossing Over and Recombination • During meiosis, chromosomes duplicate and homologous pairs synapse • Chromatids exchange homologous sections carrying alleles, producing recombinant daughter chromosomes with a different combination of alleles Equal and Unequal Crossing-Over Figure 04: Equal and unequal crossing-over for three gene segments on a chromosome • Equal Crossing-Over provides new arrangements of alleles on chromosomes but has little potential for new variation • Variation could occur if the break and repair occurred within a gene, instead of between genes as illustrated Chromosomal Rearrangements a) Deletion: Part of a chromosome breaks off and is lost b) Translocation: Part of a chromosome detaches and becomes attached to another c) Inversion: Part of a chromosome becomes switched around within the chromosome Unequal CrossingOver • During meiosis, synapsed chromosomes occasionally pair out of register with each other • Cross-over then occurs between non-homologous sections • As a result, genes are duplicated on one chromosome, and deleted on the other • Chromosomes with gene duplications provide new possibilities for gene function in eukaryotic evolution Unequal Cross-Over and the Origin of Gene Duplications Gene duplications are the source of most new genes, i.e., new loci, new blueprints Free to evolve a new function! Remember that cross-over occurs during Meiosis, so this process is primarily of benefit to sexually reproducing organisms Chromosomes With Duplications Gametes with sections of duplication bring more than a full set of normal genes to the zygote at fertilization They bring a series of duplicate loci One of the duplicated loci can continue to produce the original protein product while the other duplicate locus can accumulate mutations at no cost to the organism If any of those mutations confer an advantage, then natural selection can go to work to spread the mutant allele in the population Chromosome Inversion Two breaks occur in a single DNA strand but the improper repair reverses the sequence of the loci on one chromosome The inversion has not altered the individual gene blueprints, just their arrangement along the arm of the chromosome Crossing-Over Changes the Phenotype of Chromosomes inversion loops protect linked alleles from being separated by crossing over Figure 03: Structural chromosomal changes Chromosomal Evolution in Drosophila • Polytene chromosomes in the salivary glands provided an early methods for mapping genes to specific chromosomes Inversions Cause Problems in Meiosis The homologs cannot pair easily in this region because the sequences do not match. When they do pair and cross-over occurs, the products include large sections of duplication on one homolog and large sections of deletion on the other. Gametes that get chromosomes with large sections deleted often lead to failure of development in the resulting zygote. Heterozygous Inversions Produce Stable Linkage Groups • There is a potential evolutionary advantage to having an inverted sequence • Due to the odd physical pairing of the chromosomes at meiosis, once an inversion has become stabilized somewhere along the length of the chromosome in one of a pair of homologs, while the other contains the original sequence, further cross-over events are mechanically unlikely • So the alleles in the inverted region are then protected and passed as a unit to future generations Heterozygous Inversions Produce Stable Linkage Groups • We call these individuals “heterozygotic” for the inversion • One chromosome carries the inversion while the other homolog does not • Alleles stay neighbors fruit fly larval polytene chromosome Drosophila subobscura cline Populations of Drosophila subobscura are polymorphic for at least one inversion in five of their six chromosomes and the frequency of the inversions in the populations varies by altitude and latitude, forming clines Drosophila subobscura Genetics • Due to chance, a series of genes contributing to the phenotype of body size became involved in a heterozygotic inverted sequence • One set of alleles, a multi-locus genotype, are expressed to confer a consistent larger body size in the flies • Another set of alleles at the same inverted locus contribute to small body size Drosophila subobscura Genetics • Natural selection tends to eliminate large flies in hot dry climates and to eliminate small flies in cold wet climates • Cold and wet climates are more common the farther you move from the equator, whereas hot dry climates are more common closer to the equator • This becomes a stable microevolutionary polymorphism Inversion Frequencies Form Clines in Drosophila subobscura Est inversion favors large body size hot/dry cold/wet hot/dry cold/wet The two adapted genotypes are preserved in the two different climates because having the genes tied up in a linkage group where cross-over is very unlikely means that the population does not waste a lot of reproductive potential on offspring with a mixed genotype and therefore a blended or intermediate phenotype Instead, the populations show less variation in body size but the body size varies appropriately with climate types Condensation of Chromosomes in Muntiacus sp. Diploid chromosome sets of two species of muntjacs, small southeast Asian relatives of deer (Moschidae: Artiodactyla: Mammalia): Muntiacus reevesi (2n=46) (above) and Muntiacus muntiacus (2n=8) (below), both to the same scale. Despite enormous differences in chromosome sizes and numbers, the DNA content of cells in the two species and their morphological phenotypes are very similar. Such changes in chromosome numbers can make speciation and reproductive isolation easier. Figure 05A: Chinese muntjac deer Courtesy of Chuck Dresner/Saint Louis Zoo (2n=46) (above) and (2n=8 )(below) Figure 05B: Indian muntjac deer Courtesy of the Saint Louis Zoo Muntiacus muntjac (2n=6) is mentioned in your text Chromosomal Evolution in Primates Figure 06: Banding arrangements of the chromosomes of humans, chimpanzees, gorillas, and orangutans • G-banding (Giemsa stain) techniques allow for a similar reference set of bands in other normal chromosomes • Common banding patters imply close evolutionary relationships Reproduced from Yunis, J. J., and Prakash, O. Science 215 (1982): 1525-1530. Reprinted with permission from AAAS. Chromosomal Evolution in Primates Figure 06: Banding arrangements of the chromosomes of humans, chimpanzees, gorillas, and orangutans • Notice that the banding patterns are very similar for all the chromosomes of all the apes • Notice that humans differ in having a chromosome #2 that appears to be fused from two shorter ape chromosomes Reproduced from Yunis, J. J., and Prakash, O. Science 215 (1982): 1525-1530. Reprinted with permission from AAAS. Mutations as a Source of Genetic Variation • Mutations are normally expressed at one of two levels of gene activity – Changes within a gene product, for example, in the amino acid constitution of a particular protein – Changes in the regulation of a gene or its product • Mutations may affect the amount or rate at which a gene product is produced, or whether or not the protein is produced at all or at what points in the life of the cell Measuring Genetic Variation in Natural Populations • Phenotypic Variation – anatomy – biochemistry – physiology – development – behavior • Genotypic Variation – alleles – loci – chromosomes – genomes In most cases, one cannot infer a genotype just from the inspection or identification of a particular phenotype Indirect evidence: proteins Direct evidence: DNA Evolutionary Impact of Mutations • All mutation events increase genetic variation in populations and give natural selection the raw material from which to generate adaptive evolutionary changes • Both the mutational processes and their rates or frequencies are diverse • Evolution is driven by the combination of both these processes, mutation and selection variation in Acacia ligulata seeds Evolutionary Impact of Mutations • It is important to remember that most of mutational processes lead to decreased adaptation most of the time • Most mutations are harmful; most chromosome rearrangements are harmful; most changes in ploidy are harmful • However, when you take the long view, when there are so many species, so many individuals, and so much time (3.5 billion years), even low frequency events, such as beneficial mutations, beneficial chromosomal rearrangements, beneficial changes in genome ploidy can occur and when they do, natural selection will be there as the mechanism to see that they are preserved and spread Gene Regulation • Which genes are transcribed into messenger RNA, which transcripts are translated into proteins, and which proteins are activated, are the result of interactions that often begin with signals that initiate different genetic regulatory pathways or networks Table T02: Ways by Which Genetic Variation is Maintained or Can Change at the Level of Individual Genes Gene Regulation as a Source of Variation • Gene regulation in the bacterium Escherichia coli • The Lac Operon (Jacob & Monod, 1961, earned them the Nobel Prize in Physiology or Medicine in 1965) Figure 08A: Scheme of lac enzyme synthesis in E. coli Adapted from Strickberger, M. W. Genetics, Third edition. Macmillan, 1985. Gene Regulation as a Source of Variation lactose Figure 08B: Scheme of lac enzyme synthesis in E. coli Adapted from Strickberger, M. W. Genetics, Third edition. Macmillan, 1985. Figure 08C: Scheme of lac enzyme synthesis in E. coli Adapted from Strickberger, M. W. Genetics, Third edition. Macmillan, 1985. Gene Regulation in Eukaryotic Cells • Three major regulatory mechanisms control transcription of DNA → mRNA: – cis– trans– RNA interference (RNAi) - regulation – Minor mechanisms • Transposons • Posttranscriptional modification [ great animation on RNAi action ] Trans-Regulation • The trans-regulatory elements are the DNA sequences that encode Transcription Factors (regulatory proteins) • Trans-regulatory sequences reside on other DNA molecules than the regulated gene • These Transcription Factors (TF) can bind to the cis-regulatory elements or the CAAT and TATA boxes adjacent to a structural gene Cis-Regulation • Cis-regulatory elements reside upstream from a promoter region for a structural gene on the same DNA (chromosome) • Transcription factors (promoters, enhancers, silencers and repressors) bind to the cis-regulatory elements to encourage or discourage transcription of the structural gene • Modification of cis- and trans- regulation are important mechanisms leading to developmental and morphological change in evolution Cis- and Trans-Regulation Figure B01A: cis-regulatory elements and gene transcription in animals Figure B01B: cis-regulatory elements and gene transcription in animals Adapted from Carroll et al. From DNA To Diversity, Second edition. Blackwell Publishing, 2005. RNAi-Regulation • Small interference RNA (siRNA) molecules and microRNA (miRNA) molecules were discovered relatively recently • These short (~21 nucleotide molecules) have a variety of roles in eukaryotes including defense against viruses and transposable elements, but also exert regulatory roles in translation of proteins, cell division and cell differentiation RNAi-Regulation RNAi silencing is initiated when double-stranded RNA (dsRNA) is processed into small interfering RNAs (siRNA) between 19-26 base pairs in length by an RNaseIII enzyme called Dicer. These siRNAs are subsequently incorporated into RNA-induced silencing complexes (RISC) that target complimentary messenger RNA (mRNA) sequences for cleavage to mediate gene suppression Pre-mRNA: short stem-loop structures are formed when mRNAs are processed from primary transcripts. The main function of siRNA is cleavage of miRNA. The main function of miRNA is the inhibition of protein synthesis by blocking mRNA translation. RNAi-Regulation • Small interference RNA (siRNA) and microRNA (miRNA) molecules can increase or decrease the rate of translation • They bind to messenger RNAs and cleave them, halting transcription, when present • They can act on multiple types of mRNA in a cell so they can have wide-ranging effects • Mutations in their loci can have profound effects on phenotypes RNAi-Regulation • Because Small interference RNA (siRNA) and microRNA (miRNA) molecules can be carried by vectors (e.g., viruses) from one cell to another, there has been recent speculation that they could be agents for moving somatic mutations to germ cells • If so, this would be somewhat analogous to Darwin’s idea of gemmules and pangenesis in a modern form • We’ll have to wait to see on that idea! Posttranscriptional Modification • Recall that in Eukaryotes, after a structural gene is transcribed into pre-mRNA, it can be modified in various ways – Exons must be removed, and there can be options as to which exons are removed (RNA editing) – Addition of variable length poly-Adenine tails can affect the lifespan of the mRNA in the cytoplasm before it is degraded – Modifiers can bind to the mRNA to delay or prevent translation Posttranscriptional Modification • One of the best studied examples is in the gene libraries vertebrates carry to direct the synthesis of millions of different antibody molecules Light and Heavy Ab Chain Recombination Ig class switching Estimates of Mutation Per Genome Per Generation [Individual] Short generation times Only one cell division/generation Long generation times many cell division to produce gametes/generation Estimations are based on Nonsense Mutations. How Can Mutations Affect Fitness? • While mutation rate at any given locus is usually fairly low, since there are many hundreds of genes in most organisms, then a given individual organism is actually fairly likely to acquire one or mutations somewhere in its genome • However, a mutation will only be passed to offspring if the mutation occurs in the germ cells leading to gamete production How Can Mutations Affect Fitness? • Each human being receives approximately 60 new mutations in his/her genome from his/her parents (2011) How Can Mutations Affect Fitness? • A mutation acquired in any other cell is termed a somatic mutation, and will not be a heritable mutation, though it may have an impact on the fitness of this individual, especially if it occurred early in development, and therefore becomes widespread in tissues or organs. • That impact could be positive or, more likely, negative. Why more likely negative? • Because the normal allele or genotype has already been refined and preserved by natural selection for millions, perhaps billions of years, and most chance mutations are likely to disrupt rather than improve protein function if they have any effect at all. How Do Most Mutations Affect Fitness? • Photocopy Error: like the C. elegans study, the accumulation of many small errors leads to loss of function over generations 10 20 50 75 100 How Do Most Mutations Affect Fitness? Controls were normal worms experiencing natural selection in a competitive lab environment. Mutation Accumulation lineages were reared in a protected lab environment where all survival needs were provided Caenorhabditis elegans is a small (about 1 mm long) soil nematode found in temperate regions How Do Most Mutations Affect Fitness? • There is a complex interplay between genotype, phenotype, competition/survival and reproduction • A mutation may act at one or more than one level in the process Evolutionary Developmental Biology Hox genes • Edward B. Lewis discovered homeotic genes in DNA in the 1990s • Nobel Prize in Medicine (1995) • This work led to the new subdiscipline “Evo-Devo” • Lewis laid the groundwork for our current understanding of the universal evolutionarily conserved strategies controlling animal development Gene Regulation and Evolution • A single change in a regulatory gene that controls other genes can change how a gene network works, with dramatic consequences for the phenotype • Homeobox gene, Ultrabithorax Figure 09B: Fly with two sets of wings Figure 09A: Normal fly with halteres © Eye of Science/Photo Researchers, Inc. Gene Regulation and Evolution • Sonic hedgehog (Shh), Pax-6, and the homeobox gene Prox1 interact in the development of the Mexican tetra • Increased Shh expression reduces eye development but increases the number of taste buds, compensating for reduced vision with increased chemoreception in the blind form • Lateral line function is also expanded in the blind form, but the gene locus is unknown Figure 11: Mexican tetra Courtesy of Dr. Simon Walker, Department of Zoology, University of Oxford Figure 10B: Mexican cave fish Adapted from Franz-Odendaal, T. A., and B. K. Hall, Evol. & Devel 8 (2006): 94-100. What Can a Mutation Do? Poisonous plants can be teratogens. For instance, the skunk cabbage Veratrum californicum, naturally found Synpolydactyly (SPD) is a genetic disorder that results from growing in meadows of the Rocky mutations in one of the HOX genes. The phenotypes are mountains, can cause severe birth shown in the pictures above, which usually involves defects in the offspring of sheep developmental disorders in the fingers and toes resulting or cattle that have grazed on this in fusion and malformation. plant. These birth defects include neurological damage and cyclopia, the fusion of two eyes into one. Humans and other mammals are also susceptible to this teratogen. Transposable Elements • Barbara McClintock (19021992) • Discovered transposons and gene regulation in maize between 1944 and 1953 • Her work was ignored and misunderstood for decades, but . . . • Nobel Prize for Physiology or Medicine (1983) Figure B02A: Mosaic color patterns Figure B02B: Mosaic color patterns of of seeds in cobs of maize seeds in cobs of maize © Mike Flippo/ShutterStock, Inc. © Greg30127/Dreamstime.com Transposable Elements • Transposons produce special transposase enzymes that allow it to insert copies of itself into various target sites in an organism’s nuclear genome Transposable Elements Figure 12: E. Coli-derived IS1 transposon into the maize genome Adapted from Strickberger, M. W. Genetics, Third edition. Macmillan, 1985. It is probably best to think of Transposable Elements as molecular parasites which may accidentally create adaptive (or harmful) mutations and phenotypic variations, and act as agents of Horizontal Gene Transfer in Eukaryotes. There is still much to be learned about them. Transposable Elements • In primates, an Alu sequence is present in perhaps more than thousands of copies in each diploid human cell, a genetic synapomorphy for primates Summary: Types of Mutation with Significant Evolutionary Impact In the cases of gene duplication and polyploidy, “extra” genes become available to mutate, possibly providing new preadaptations/proteins, while the original genes continue to code for the original functional proteins. Mutations are Necessary for Evolution Chapter 12 End How Are Tetraploid Individuals Produced in Plants? • When a tetraploid individual matures and produces gametes by meiosis, haploid gametes with the 2N chromosome number form easily and unite to produce more tetraploid individuals. hosta Chromosomal Rearrangements reciprocal crossover • Translocation chromosomes produce visible evidence of the process of recombination during meiosis