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Chapter 15 Linkage and Chromosomes Lecture Presentations by Nicole Tunbridge and © 2021 Pearson Education Ltd....

Chapter 15 Linkage and Chromosomes Lecture Presentations by Nicole Tunbridge and © 2021 Pearson Education Ltd. Kathleen Fitzpatrick Figure 15.1a © 2021 Pearson Education Ltd. Figure 15.1b © 2021 Pearson Education Ltd. Concept 15.1: Mendelian inheritance has its physical basis in the behavior of chromosomes Mendel’s proposed “hereditary units” were only theoretical in 1860 Soon, biologists saw parallels between chromosome behavior and the behavior of the proposed factors Around 1902, Sutton and Boveri and others independently noted these parallels and began to develop the chromosome theory of inheritance © 2021 Pearson Education Ltd.  The first solid evidence associating a specific gene with a specific chromosome came in the early 1900s from the work of Thomas Hunt Morgan His early experiments provided convincing evidence that the chromosomes are the location of Mendel’s heritable factors © 2021 Pearson Education Ltd. Morgan’s Choice of Experimental Organism For his work, Morgan chose to study Drosophila melanogaster, a common species of fruit fly Several characteristics make fruit flies a convenient organism for genetic studies: – They produce many offspring – A generation can be bred every two weeks – They have only four pairs of chromosomes © 2021 Pearson Education Ltd.  Morgan noted wild type, or normal, phenotypes that were common in the fly populations Traits alternative to the wild type are called mutant phenotypes The first mutant Morgan discovered was a fly with white eyes instead of the wild-type red eyes © 2021 Pearson Education Ltd. Figure 15.2 © 2021 Pearson Education Ltd. Correlating Behavior of a Gene’s Alleles with Behavior of a Chromosome Pair: Scientific Inquiry In one experiment, Morgan mated male flies with white eyes (mutant) with female flies with red eyes (wild type) – The F1 generation all had red eyes – The F2 generation showed a 3:1 red to white eye ratio, but only males had white eyes © 2021 Pearson Education Ltd.  Morgan reasoned that the white-eyed mutant allele must be located on the X chromosome Female flies have two X chromosomes (XX) while males have one X and one Y (XY) Morgan’s finding supported the chromosome theory of inheritance © 2021 Pearson Education Ltd. Figure 15.3 © 2021 Pearson Education Ltd. Figure 15.4 © 2021 Pearson Education Ltd. Concept 15.2: Sex-linked genes exhibit unique patterns of inheritance Morgan’s discovery of a trait that correlated with the sex of flies was key to the development of the chromosome theory of inheritance © 2021 Pearson Education Ltd. The Chromosomal Basis of Sex Humans and other mammals have two types of sex chromosomes: a larger X chromosome and a smaller Y chromosome A person with two X chromosomes usually develops anatomy we associate with the “female” sex “Male” properties are associated with the inheritance of one X and one Y The X-Y system is not the only chromosomal system of sex determination © 2021 Pearson Education Ltd. Figure 15.5 © 2021 Pearson Education Ltd. Figure 15.6 © 2021 Pearson Education Ltd.  Short segments at the ends of the Y chromosomes are homologous with the X, allowing the two to behave like homologs during meiosis in males In mammals, a gene on the Y chromosome called SRY (sex-determining region on the Y) is responsible for development of the testes in an embryo © 2021 Pearson Education Ltd.  A gene that is located on either sex chromosome is called a sex-linked gene Genes on the Y chromosome are called Y-linked genes Only 78 genes, coding for about 25 proteins, have been identified on the human Y chromosome Genes on the X chromosome are called X-linked genes; the human X chromosome contains about 1,100 genes © 2021 Pearson Education Ltd. Inheritance of X-Linked Genes X chromosomes have genes for many characters unrelated to sex Many Y-linked genes are related to sex determination © 2021 Pearson Education Ltd.  X-linked genes follow a specific pattern of inheritance For a recessive X-linked trait to be expressed, – a female needs two copies of the allele (homozygous) – a male needs only one copy of the allele (hemizygous) X-linked recessive disorders are much more common in males than in females © 2021 Pearson Education Ltd. Figure 15.7 © 2021 Pearson Education Ltd.  Some disorders caused by recessive alleles on the X chromosome in humans: – Color blindness (mostly X-linked) – Duchenne muscular dystrophy – Hemophilia © 2021 Pearson Education Ltd. X Inactivation in Female Mammals In mammalian females, one of the two X chromosomes in each cell is randomly inactivated during embryonic development The inactive X condenses into a Barr body If a female is heterozygous for a particular gene located on the X chromosome, she will be a mosaic for that character © 2021 Pearson Education Ltd.  Inactivation of an X chromosome involves modification of the DNA and proteins bound to it called histones A part of the chromosome contains several genes involved in the inactivation process One of the genes there becomes active only on the chromosome that will be inactivated The gene is called XIST (X-inactive specific transcript) © 2021 Pearson Education Ltd. Figure 15.8 © 2021 Pearson Education Ltd. Concept 15.3: Linked genes tend to be inherited together because they are located near each other on the same chromosome Each chromosome has hundreds or thousands of genes (except the Y chromosome) Genes that are located on the same chromosome tend to be inherited together and are called linked genes © 2021 Pearson Education Ltd. How Linkage Affects Inheritance Morgan did experiments with fruit flies to see how linkage affects inheritance of two characters Morgan crossed flies that differed in traits of body color and wing size The first cross was a P generation cross to generate F1 dihybrid flies The second was a testcross © 2021 Pearson Education Ltd. Figure 15.9 © 2021 Pearson Education Ltd.  The resulting flies had a much higher than expected proportion of the combination of traits seen in the P generation flies (parental phenotypes) He concluded that these genes do not assort independently and reasoned that they were on the same chromosome © 2021 Pearson Education Ltd. Figure 15.UN01 © 2021 Pearson Education Ltd.  Nonparental phenotypes were also produced in the testcross, suggesting that the two traits could be separated sometimes This involves genetic recombination, the production of offspring with combinations of traits differing from either parent © 2021 Pearson Education Ltd. Genetic Recombination and Linkage The genetic findings of Mendel and Morgan relate to the chromosomal basis of recombination © 2021 Pearson Education Ltd. Recombination of Unlinked Genes: Independent Assortment of Chromosomes Offspring with a phenotype matching one of the parental (P) phenotypes are called parental types Offspring with nonparental phenotypes (new combinations of traits) are called recombinant types, or recombinants A 50% frequency of recombination is observed for any two genes on different chromosomes © 2021 Pearson Education Ltd. Figure 15.UN02 © 2021 Pearson Education Ltd. Recombination of Linked Genes: Crossing Over Morgan observed that although some genes are linked, nonparental allele combinations are still produced He proposed that some process must occasionally break the physical connection between genes on the same chromosome That mechanism was the crossing over of homologous chromosomes © 2021 Pearson Education Ltd. Figure 15.10 © 2021 Pearson Education Ltd. Animation: Linked Genes and Crossing Over © 2021 Pearson Education Ltd. New Combinations of Alleles: Variation for Natural Selection Recombinant chromosomes bring alleles together in new combinations in gametes Random fertilization increases even further the number of variant combinations that can be produced This abundance of genetic variation is the raw material upon which natural selection works © 2021 Pearson Education Ltd. Mapping the Distance Between Genes Using Recombination Data: Scientific Inquiry Alfred Sturtevant, one of Morgan’s students, constructed a genetic map, an ordered list of the genetic loci along a particular chromosome Sturtevant predicted that the farther apart two genes are, the higher the probability that a crossover will occur between them and therefore the higher the recombination frequency © 2021 Pearson Education Ltd.  A linkage map is a genetic map of a chromosome based on recombination frequencies Distances between genes can be expressed as map units; one map unit represents a 1% recombination frequency Map units indicate relative distance and order, not precise locations of genes © 2021 Pearson Education Ltd. Figure 15.11 © 2021 Pearson Education Ltd.  Genes that are far apart on the same chromosome can have a recombination frequency near 50% Such genes are physically linked, but genetically unlinked, and behave as if found on different chromosomes © 2021 Pearson Education Ltd.  Sturtevant used recombination frequencies to make linkage maps of fruit fly genes They found that the genes clustered into four groups of linked genes (linkage groups) The linkage maps, combined with the fact that there are four chromosomes in Drosophila, provided additional evidence that genes are located on chromosomes © 2021 Pearson Education Ltd. Figure 15.12 © 2021 Pearson Education Ltd. Concept 15.4: Alterations of chromosome number or structure cause some genetic disorders Large-scale chromosomal alterations in humans and other mammals often lead to spontaneous abortions (miscarriages) or cause a variety of developmental disorders Plants tolerate such genetic changes better than animals do © 2021 Pearson Education Ltd. Abnormal Chromosome Number In nondisjunction, pairs of homologous chromosomes do not separate normally during meiosis As a result, one gamete receives two of the same type of chromosome, and another gamete receives no copy © 2021 Pearson Education Ltd. Figure 15.13 © 2021 Pearson Education Ltd. Video: Nondisjunction in Mitosis © 2021 Pearson Education Ltd.  Aneuploidy results from the fertilization of gametes in which nondisjunction occurred Offspring with this condition have an abnormal number of a particular chromosome © 2021 Pearson Education Ltd.  A monosomic zygote has only one copy of a particular chromosome A trisomic zygote has three copies of a particular chromosome © 2021 Pearson Education Ltd.  Polyploidy is a condition in which an organism has more than two complete sets of chromosomes – Triploidy (3n) is three sets of chromosomes – Tetraploidy (4n) is four sets of chromosomes Polyploidy is common in plants, but not animals Polyploids are more normal in appearance than aneuploids © 2021 Pearson Education Ltd. Alterations of Chromosome Structure Breakage of a chromosome can lead to four types of changes in chromosome structure: – Deletion removes a chromosomal fragment – Duplication repeats a segment – Inversion reverses orientation of a segment within a chromosome – Translocation moves a segment from one chromosome to another © 2021 Pearson Education Ltd. Figure 15.14 © 2021 Pearson Education Ltd. Human Disorders Due to Chromosomal Alterations Alterations of chromosome number and structure are associated with some serious disorders Some types of aneuploidy appear to upset the genetic balance less than others, resulting in individuals surviving to birth and beyond These surviving individuals have a set of symptoms, or syndrome, characteristic of the type of aneuploidy © 2021 Pearson Education Ltd. Down Syndrome (Trisomy 21) Down syndrome is an aneuploid condition that results from three copies of chromosome 21 It affects about one out of every 830 children born in the United States The frequency of Down syndrome increases with the age of the mother, a correlation that has not been explained © 2021 Pearson Education Ltd. Figure 15.15 © 2021 Pearson Education Ltd. Aneuploidy of Sex Chromosomes Nondisjunction of sex chromosomes produces a variety of aneuploid conditions Klinefelter syndrome is the result of an extra chromosome in a male, producing XXY individuals About one in 1,000 males is XYY; these males do not exhibit any syndrome © 2021 Pearson Education Ltd.  XXX females occur with a frequency of about one in 1,000 They are healthy, with no unusual physical features, though they are at risk for learning disabilities Monosomy X, called Turner syndrome, produces X0 females, who are sterile; it is the only known viable monosomy in humans © 2021 Pearson Education Ltd. Disorders Caused by Structurally Altered Chromosomes The syndrome cri du chat (“cry of the cat”), results from a specific deletion in chromosome 5 A child born with this syndrome is severely intellectually disabled and has a catlike cry; individuals usually die in infancy or early childhood Certain cancers, including chronic myelogenous leukemia (CML), are caused by translocations of chromosomes © 2021 Pearson Education Ltd. Figure 15.16 © 2021 Pearson Education Ltd. Concept 15.5: Some inheritance patterns are exceptions to standard Mendelian inheritance There are two normally occurring exceptions to Mendelian genetics One exception involves genes located in the nucleus, and the other involves genes located outside the nucleus In both cases, the sex of the parent contributing an allele is a factor in the pattern of inheritance © 2021 Pearson Education Ltd. Genomic Imprinting For a few mammalian traits, the phenotype depends on which parent passed along the alleles for those traits Such variation in phenotype is called genomic imprinting Genomic imprinting involves the silencing of certain genes depending on which parent passes them on Most imprinted genes are on autosomes © 2021 Pearson Education Ltd.  The mouse gene for insulin-like growth factor 2 (Igf2) was one of the first imprinted genes to be identified Only the paternal allele of this gene is expressed © 2021 Pearson Education Ltd. Figure 15.17 © 2021 Pearson Education Ltd.  It seems that imprinting is the result of the methylation (addition of —CH3 groups) of cysteine nucleotides Genomic imprinting may affect only a small fraction of mammalian genes Most imprinted genes are critical for embryonic development © 2021 Pearson Education Ltd. Inheritance of Organelle Genes Extranuclear genes (or cytoplasmic genes) are found in organelles in the cytoplasm Mitochondria, as well as chloroplasts, and other plant plastids carry small circular DNA molecules Extranuclear genes are inherited maternally because the zygote’s cytoplasm comes from the egg The first evidence of extranuclear genes came from studies on the inheritance of yellow or white patches on leaves of an otherwise green plant © 2021 Pearson Education Ltd. Figure 15.18 © 2021 Pearson Education Ltd.  Some defects in mitochondrial genes prevent cells from making enough ATP and result in diseases that affect the muscular and nervous systems – For example, mitochondrial myopathy and Leber’s hereditary optic neuropathy © 2021 Pearson Education Ltd.  It may be possible to avoid passing along mitochondrial disorders The chromosomes from the egg of an affected mother could be transferred to an egg of a healthy donor, generating a “two-mother” egg This egg could then be fertilized by sperm from the prospective father and transplanted to the womb of the prospective mother © 2021 Pearson Education Ltd. Figure 15.UN01a © 2021 Pearson Education Ltd. Figure 15.UN01b © 2021 Pearson Education Ltd. Figure 15.UN01c © 2021 Pearson Education Ltd. Figure 15.UN02 © 2021 Pearson Education Ltd. Figure 15.UN03 © 2021 Pearson Education Ltd.