1. PowerPoint Presentation Materials to accompany Genetics: Analysis and Principles Robert J. Brooker Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display CHAPTER 7 NON-MENDELIAN INHERITANCE

2. INTRODUCTION In this chapter we will discuss additional (even bizarre) patterns of inheritance that deviate from a Mendelian pattern Maternal effect and epigenetic inheritance Involve genes in the nucleus X-inactivation (Dosage compansation) Genomic imprinting Extranuclear inheritance Involves genes in organelles other than the nucleus Mitochondria Chloroplasts 7-3 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

3. Maternal effect refers to an inheritance pattern for certain nuclear genes in which the genotype of the mother directly determines the phenotype of her offspring Surprisingly, the genotypes of the father and offspring themselves do not affect the phenotype of the offspring This phenomenon is due to the accumulation of gene products that the mother provides to her developing eggs 7-4 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 7.1 MATERNAL EFFECT

4. 7-5 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display The first example of a maternal effect gene was discovered in the 1920s by A. E. Boycott He was studying morphological features of the water snail, Limnaea peregra In this species, the shell and internal organs can be arranged in one of two directions Right-handed (dextral) Left-handed (sinistral) The dextral orientation is more common and dominant The snail’s body plan curvature depends on the cleavage pattern of the egg immediately after fertilization Figure 7.1 describes Boycott’s experiment

6. 7-6 Reciprocal cross Figure 7.1 A 3:1 phenotypic ratio would be predicted by a Mendelian pattern of inheritance

7. 7-7 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Alfred Sturtevant later explained the incongruity with Mendelian inheritance Snail coiling is due to a maternal effect gene that exists as dextral (D) and sinistral (d) alelles The phenotype of the offspring depended solely on the genotype of the mother His conclusions were drawn from the inheritance patterns of the F 2 and F 3 generations

8. 7-8 Figure 7.1 The dominant allele, D, caused ALL the F2 offspring to be dextral F1 mothers are Dd This explains this 3:1 ratio F2 mothers include 3 with the D allele and 1 with the d allele Reciprocal cross

9. 7-9 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Thus, in this example DD or Dd mothers produce dextral offspring dd mothers produce sinistral offspring The phenotype of the progeny is determined by the mother’s genotype NOT phenotype The genotypes of the father and offspring do not affect the phenotype of the offspring

10. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display The non-Mendelian inheritance pattern of maternal effect genes can be explained by the process of oogenesis in female animals Maturing animal oocytes are surrounded by maternal cells that provide them with nutrients These nurse cells are diploid, whereas the oocyte becomes haploid In the example of Figure 7.2a A female is heterozygous for the snail-coiling maternal effect gene The haploid oocyte received the d allele in meiosis 7-10

11. Figure 7.2 7-11 The gene products are a reflection of the genotype of the mother They are transported to the cytoplasm of the oocyte where they persist for a significant time after the egg has been fertilized Thus influencing the early developmental stages of the embryo

12. Figure 7.2 7-12 D gene products cause egg cleavage that promotes a right-handed body plan

13. 7-13 Figure 7.2 d gene products cause egg cleavage that promotes a left- handed body plan Even if the egg is fertilized by sperm carrying the D allele The sperm’s genotype is irrelevant because the expression of the sperm’s gene would be too late

14. 7-14 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Maternal effect genes encode RNA and proteins that play important roles in the early steps of embryogenesis For example-Cell division, Cleavage pattern, Body Axis determination Accumulation before fertilization allows these steps to proceed very quickly after fertilization Therefore defective alleles in maternal gene effects tend to have a dramatic effect on the phenotype of the individual In Drosophila, geneticists have identified several dozen maternal effect genes These have profound effects on the early stages of development

15. Epigenetic inheritance refers to a pattern in which a modification occurs to a nuclear gene or chromosome that alters gene expression However, the expression is not permanently changed over the course of many generations That is because the DNA sequence does not change Epigenetic changes are caused by DNA and chromosomal modifications These can occur during oogenesis, spermatogenesis or early embryonic development Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 7.2 EPIGENETIC INHERITANCE 7-15

16. The left micrograph shows the Barr body on the periphery of a human nucleus after staining with a DNA-specific dye

17. The fur pattern of a calico cat

18. The purpose of dosage compensation is to offset differences in the number of active sex chromosomes Depending on the species, dosage compensation occurs via different mechanisms Refer to Table 7.1 7-16 Dosage Compensation Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

19. 7-17

20. Dosage compensation is not well understood in some species, such as birds and fish In birds, the sex chromosomes are the Z, a large chromosome containing many genes W, a microchromosome containing few genes Males are ZZ; females are ZW It appears that the Z chromosome in males does not undergo condensation like one of the X chromosomes in female mammals Different studies have shown presence and absence of dosage compensation in birds May occur only on specific genes May be accomplished through histone modification 7-18 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

21. In 1949, Murray Barr and Ewart Bertram identified a highly condensed structure in the interphase nuclei of somatic cells in female cats but not in male cats This structure became known as the Barr body (Figure 7.3a) In 1960, Susumu Ohno correctly proposed that the Barr body is a highly condensed X chromosome In 1961, Mary Lyon proposed that dosage compensation in mammals occurs by the inactivation of a single X chromosome in females 7-19 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Dosage compensation in mammals

22. The left micrograph shows the Barr body on the periphery of a human nucleus after staining with a DNA-specific dye

23. The mechanism of X inactivation, also known as the Lyon hypothesis, is schematically illustrated in Figure 7.4 7-20 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display The example involves a white and black variegated coat color found in certain strains of mice A female mouse has inherited two X chromosomes One from its mother that carries an allele conferring white coat color (X b ) One from its father that carries an allele conferring black coat color (X B )

24. 7-21 Figure 7.4 At an early stage of embryonic development The epithelial cells derived from this embryonic cell will produce a patch of white fur While those from this will produce a patch of black fur

25. During X chromosome inactivation, the DNA becomes highly compacted Most genes on the inactivated X cannot be expressed When this inactivated X is replicated during cell division Both copies remain highly compacted and inactive In a similar fashion, X inactivation is passed along to all future somatic cells Another example of variegated coat color Is found in calico cats Refer to Figure 7.3b 7-22 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

26. The fur pattern of a calico cat

27. In 1963, Ronald Davidson, Harold Nitowsky and Barton Childs set out to test the Lyon hypothesis at the cellular level To do so they analyzed the expression of a human X-linked gene The gene encodes glucose-6-phosphate dehydrogenase (G-6-PD), an enzyme used in sugar metabolism 7-23 The Lyon Hypothesis Put to the Test Experiment 7A Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

28. Biochemists had found that individuals vary with regards to the G-6-PD enzyme This variation can be detected when the enzyme is subjected to agarose gel electrophoresis One G-6-PD allele encodes an enzyme that migrates very quickly The “fast” enzyme Another allele encodes an enzyme that migrates slowly The “slow” enzyme The two types of enzymes have minor differences in their structures These do not significantly affect G-6-PD function 7-24 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

29. 7-25 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Thus heterozygous adult females produce both types of enzymes Hemizygous males produce either the fast or the slow type

30. These results are consistent with the hypothesis that X inactivation has already occurred in any given epithelial cell AND This pattern of inactivation is passed to all of the cell’s progeny 7-30 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Interpreting the Data

31. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display X Inactivation Depends on Xic, Xist, TsiX and Xce Researchers have found that mammalian cells can count their X chromosomes and allow only one of them to remain active Additional X chromosomes are converted to Barr bodies 7-31 Phenotype Sex Chromosome Composition Number of Barr bodies Normal femaleXX1 Normal maleXY0 Turner syndrome (female)X00 Triple X syndrome (female)XXX2 Klinefelter syndrome (male)XXY1

33. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display The genetic control of inactivation is not entirely understood at the molecular level However, a short region on the X chromosome termed the X-inactivation center (Xic) plays a critical role For inactivation to occur, each X chromosome must have a Xic region (Figure 7.7, slide 7-35) The Xic region contains a gene named Xist (for X- inactive specific transcript) The Xist gene is only expressed on the inactive X chromosome It does not encode a protein It codes for a long RNA, which coats the inactive X chromosome Other proteins will then bind and promote chromosomal compaction into a Barr body 7-32

34. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Figure 7.7 7-35 Promotes compaction Prevents compaction May regulate the transcription of the Xic region Thereby influences the choice of the active X chromosome

35. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display A gene designated TsiX also plays a role in chromosome choice It is located in the Xic region It is expressed only during early embryonic development It encodes an RNA complementary to Xist RNA Termed antisense RNA (where Xist RNA is the sense RNA) Tsix antisense RNA is believed to bind to Xist sense RNA and inhibit its function In other words, TsiX RNA prevent X chromosome inactivation The choice of which X is inactivated involves a complex interplay between Xist and Tsix The exact mechanism is not understood 7-33

36. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display A second region termed the X chromosome controlling element (Xce) affects the choice of the X chromosome to be inactivated Xce is close to and may even overlap Xic Xce may bind proteins that regulate the genes of the Xic A female heterozygous for different Xce alleles will have a skewed X-inactivation The X chromosome that carries a strong Xce allele is more likely to remain active than one with a weak Xce allele 7-34

37. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Figure 7.7 7-35 Promotes compaction Prevents compaction May regulate the transcription of the Xic region Thereby influences the choice of the active X chromosome

38. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display The process of X inactivation can be divided into three stages Initiation One of the X chromosomes is targeted to be inactive Spreading The chosen X chromosome is inactivated Maintenance The inactivated X chromosome is maintained as such during future cell divisions Refer to Figure 7.8 7-36

39. 7-37 Figure 7.8 The Barr body is replicated and both copies remain compacted Initiation. X countingSpreading

40. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display A few genes on the inactivated X chromosome are expressed in the somatic cells of adult female mammals These genes escape the effects of X inactivation They include Xist Pseudoautosomal genes Dosage compensation in this case is unnecessary because these genes are located both on the X and Y Up to a quarter of X genes in humans may escape full inactivation The mechanism is not understood May involve loosening of chromatin in specific regions 7-38

41. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Genomic Imprinting Genomic imprinting is a phenomenon in which expression of a gene depends on whether it is inherited from the male or the female parent Imprinted genes follow a non-Mendelian pattern of inheritance Depending on how the genes are “marked”, the offspring expresses either the maternally-inherited or the paternally-inherited allele Not both This is termed monoallelic expression 7-39

42. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Let’s consider the following example in mice: The Igf-2 gene encodes a growth hormone called insulin- like growth factor 2 A functional Igf-2 gene is necessary for a normal size Imprinting results in the expression of the paternal but not the maternal allele The paternal allele is transcribed into RNA The maternal allele is not transcribed Igf-2m is a mutant allele that yields a partially defective protein This may cause a mouse to be dwarf depending on whether it inherits the mutant allele from its father or mother Refer to Figure 7.9 7-40

43. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 7-41

44. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Genomic imprinting occurs in several species including mammals, insects and plants It may involve A single gene A part of a chromosome An entire chromosome Even all the chromosomes from one parent It can be used for X inactivation in some species 7-44

45. Genomic imprinting must involve a marking process At the molecular level, the imprinting of several genes is known to involve differentially methylated regions (DMRs) These are located near the imprinted genes They are methylated either in the oocyte or sperm Not both They contain binding sites for one or more transcriptional factors Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Imprinting and DNA Methylation 7-45

46. For most genes, methylation at a DMR results in inhibition of gene expression Methylation could Enhance the binding of proteins that inhibit transcription and/or Inhibit the binding of proteins that enhance transcription Because of this, imprinting is usually described as a process that silences gene expression by preventing transcription However, this is not always the case Refer to Figure 7.11 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 7-46

47. Let’s consider two imprinted genes in humans, H19 and Igf-2 They lie close to each other on human chromosome 11 Appear to be controlled by the same DMR Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 7-47 This DMR Is ~ 2000 bp Contains binding sites for proteins that regulate the transcription of both genes Is highly methylated on the paternally inherited chromosome Methylation silences the H19 gene and activates the Igf-2 gene

48. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 7-48 Figure 7.11a Only binds to unmethylated DMR H19 gene activated Igf-2 gene silenced Only binds to methylated DMR H19 gene silenced Igf-2 gene activated

49. 7-49 Figure 7.11b Methylation patterns in somatic cells and gametes of male and female offspring Haploid female gametes transmit an unmethylated DMR Haploid male gametes transmit a methylated DMR

52. To date, imprinting has been identified in dozens of mammalian genes 7-50 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display However, the biological significance of genomic imprinting is still a matter of speculation

53. Imprinting does play a role in the inheritance of certain human diseases such as Prader-Willi syndrome (PWS) and Angelman syndrome (AS) PWS is characterized by Reduced motor function Obesity Mental deficiencies AS is characterized by Hyperactivity Unusual seizures Repetitive symmetrical muscle movements Mental deficiencies Most commonly, PWS and AS involve a small deletion in chromosome 15 If it is inherited from the mother, it leads to AS If it is inherited from the father, it leads to PWS 7-51 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

54. Researchers have discovered that this region contains closely linked but distinct genes These are maternally or paternally imprinted 7-52 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display AS results from the lack of expression of a single gene, UBE3A UBE3A encodes a protein called EA-6P that transfers small ubiquitin molecules to certain proteins to target their degradation The gene is paternally imprinted (silenced) PWS results (most likely) from the lack of expression of a single gene, designated SNRNP SNRNP encodes a small nuclear ribonucleoprotein which is a complex that controls gene splicing This protein is necessary for the synthesis of critical proteins in the brain The gene is maternally imprinted (silenced)

57. 7-53 Figure 7.12

58. Extranuclear inheritance refers to inheritance patterns involving genetic material outside the nucleus The two most important examples are due to genetic material within organelles Mitochondria and chloroplasts These organelles are found in the cytoplasm Therefore, extranuclear inheritance is also termed cytoplasmic inheritance Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 7.3 EXTRANUCLEAR INHERITANCE 7-54

59. The genetic material of mitochondria and chloroplasts is located in a region called the nucleoid Refer to Figure 7.13 The genome is composed of a single circular chromosome containing double-stranded DNA Note: A nucleoid can contain more than one chromosome An organelle can contain more than one nucleoid Chloroplasts tend to have more nucleoids per organelle than mitochondria Refer to Table 7.3 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 7-55

61. 7-56 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

62. Besides variation in copy number, the sizes of organellar genomes also vary greatly among different species There is a 400-fold variation in the size of mitochondrial genomes There is also a substantial variation in size of chloroplast genomes In general, mitochondrial genomes are Fairly small in animals Intermediate in size in fungi, algae and protists Fairly large in plants Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 7-57

63. The main function of mitochondria is oxidative phosphorylation A process used to generate ATP (adenosine triphosphate) ATP is used as an energy source to drive cellular reactions The genetic material in mitochondria is referred to as mtDNA The human mtDNA consists of only 17,000 bp (Figure 7.14) It carries relatively few genes rRNA and tRNA genes 13 genes that function in oxidative phosphorylation Note: Most mitochondrial proteins are encoded by genes in the nucleus These proteins are made in the cytoplasm, then transported into the mitochondria Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 7-58

64. 7-59 Figure 7.14 Necessary for synthesis of proteins inside the mitochondrion Function in oxidative phosphorylation

65. The main function of chloroplasts is photosynthesis The genetic material in chloroplasts is referred to as cpDNA It is typically about 10 times larger than the mitochondrial genome of animal cells The cpDNA of tobacco plant consists of 156,000 bp It carries between 110 and 120 different genes rRNA and tRNA genes Many genes that are required for photosynthesis As with mitochondria, many chloroplast proteins are encoded by genes in the nucleus These proteins contain chloroplast-targeting signals that direct them from the cytoplasm into the chloroplast Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 7-60

66. 7-61 Figure 7.15 A genetic map of the tobacco chloroplast genome Genes designated ORF (open reading frame) encode polypeptides with unknown functions

67. Carl Correns discovered that pigmentation in Mirabilis jalapa (the four o’clock plant) shows a non- Mendelian pattern of inheritance Leaves could be green, white or variegated (with both green and white sectors) Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 7-62 Maternal Inheritance in the Four- o’clock Plant Correns determined that the pigmentation of the offspring depended solely on the maternal parent and not at all on the paternal parent This is termed maternal inheritance different than maternal effect Refer to Figure 7.16

68. 7-63 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Figure 7.16

69. 7-64 In this example, maternal inheritance occurs because the chloroplasts are transmitted only through the cytoplasm of the egg The pollen grains do not transmit chloroplasts to the offspring The phenotype of leaves can be explained by the types of chloroplasts found in leaf cells Green phenotype is the wild-type Due to normal chloroplasts that can make green pigment White phenotype is the mutant Due to a mutation that prevents the synthesis of the green pigment A cell can contain both types of chloroplasts A condition termed heteroplasmy In this case, the leaf would be green Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

70. 7-65 Figure 7.17 provides a cellular explanation for the variegated phenotype in Mirabilis jalapa Consider a fertilized egg that inherited two types of chloroplast Green and white As the plant grows, the chloroplasts are irregularly distributed to daughter cells Sometimes, a cell may receive only white chloroplasts Such a cell will continue to divide and produce a white sector Cells that contain only green chloroplasts or a combination of green and white will ultimately produce green sectors Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display

71. 7-66 Figure 7.17

72. Mutations that yield defective mitochondria are expected to make cells grow much more slowly Boris Ephrussi and his colleagues identified Saccharomyces cerevisiae mutants that have such a phenotype These were called petites because they formed small colonies on agar plates Wild-type strains formed larger colonies Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 7-67 The Petite Trait in Yeast

73. Biochemical and physiological evidence indicated that petite mutants had defective mitochondria Genetic analyses showed that petite mutants are inherited in different ways Two main types of mutants were identified 1. Segregational mutants Have mutations in genes located in the nucleus Segregate in a Mendelian manner in meiosis Refer to Figure 7.18a 2. Vegetative mutants Have mutations in genes located in the mitochondrial genome Show a non-Mendelian pattern of inheritance Refer to Figure 7.18b Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 7-68

74. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 7-69 Figure 7.18 Yeast come in two mating types: a and  Thus, Euphressi was able to cross yeast belonging to two different strains Zygote then meiosis Each resulting tetrad shows a 2:2 ratio of wild-type to petite This result is typical of Mendelian inheritance

75. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 7-70 Figure 7.18 Euphressi discovered two types of vegetative petites Neutral and Suppressive Zygote then meiosis Each resulting tetrad shows a 4:0 ratio of wild-type to petite Zygote then meiosis Each resulting tetrad shows a 0:4 ratio of wild-type to petite These results contradict the normal 2:2 ratio expected for the segregation of Mendelian traits

76. Researchers later found that Neutral petites lack most of their mitochondrial DNA Suppressive petites lack only small segments of mtDNA When two yeast cells are mated, offspring inherit mitochondria from both parents Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 7-71

77. Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 7-72 Progeny have both “wild type” and “neutral petite” mitochondria They display a normal phenotype because of the wild type mitochondria Progeny have both “wild type” and “suppressive petite” mitochondria So how come only petite colonies are produced? Two possibilities i. Suppressive petite mitochondria could replicate faster than wild-type mitochondria ii. Recombination between wild-type and petite mtDNA may ultimately produce defects in the wild-type mitochondria Figure 7.18

78. The unicellular alga Chlamydomonas reinhardtii is a model organism It contains a single chloroplast Occupies ~ 40% of the cell’s volume Most strains are sensitive to the antibiotic streptomycin (sm s ) In 1954, Ruth Sager identified a mutant that was resistant to streptomycin (sm r ) Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 7-73 Inheritance of Chloroplasts in Algae

79. Like yeast, Chlamydomonas can be found in two mating types mt + and mt – Mating type is due to nuclear inheritance It segregates in a 1:1 manner Sager and her colleagues discovered that “resistance to streptomycin” was not inherited in a Mendelian manner sm r was inherited from the mt + parent but not from the mt – parent In subsequent studies, they mapped several genes, including the sm r gene, to the chloroplast chromosome Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 7-74

80. 7-75 Figure 7.19 Because the mt + strain was sm r Because the mt + strain was sm s

81. The pattern of inheritance of mitochondria and chloroplasts varies among different species Heterogamous species Produce two kinds of gametes Female gamete  Large Provides most of the cytoplasm of the zygote Male gamete  Small Provides little more than a nucleus In these species, organelles are typically inherited from the mother Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 7-76 The Pattern of Inheritance of Organelles

82. 7-77

83. Species with maternal inheritance may, on occasion, exhibit paternal leakage The paternal parent provides mitochondria through the sperm In the mouse, for example, 1-4 paternal mitochondria are inherited for every 100,000 maternal mitochondria per generation of offspring Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 7-78 The Pattern of Inheritance of Organelles

84. Human mtDNA is transmitted from mother to offspring via the cytoplasm of the egg Therefore, the transmission of human mitochondrial diseases follows a strict maternal inheritance pattern Several human mitochondrial diseases have been discovered These are typically chronic degenerative disorders affecting the brain, heart, muscles, kidneys and endocrine glands Example: Leber’s hereditary optic neuropathy (LHON) Affects the optic nerve May lead to progressive loss of vision in one or both eyes LHON is caused by mutations in several different mitochondrial genes Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 7-79 Human Mitochondrial Diseases

85. The endosymbiosis theory describes the evolutionary origin of mitochondria and chloroplasts These organelles originated when bacteria took up residence within a primordial eukaryotic cell chloroplasts originated as cyanobacterium mitochondria originated as Gram-negative nonsulfur purple bacteria During evolution, the characteristic of the intracellular bacterial cell gradually changed to that of the organelle The endosymbiotic origin of organelles is supported by several observations These include Organelles have circular chromosomes (like bacteria) Organelle genes are more similar to bacterial genes than to those found within the nucleus Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 7-80 The Endosymbiosis Theory

86. 7-81 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display Figure 7.20 The eukaryotic cell was now able to undergo phtosynthesis The eukaryotic cell was now able to synthesize greater amounts of ATP The bacterial cells may have gained a more stable environment with more nutrients

87. During the evolution of eukaryotic species, most genes originally found in the bacterial genome have been lost or transferred to the nucleus Modern day mitochondria and chloroplasts have lost most of the genes still found in present-day cyanobacteria and purple bacteria The gene transfer has primarily been unidirectional From the organelles to the nucleus In addition, gene transfer can occur between organelles Between two mitochondria, two chloroplasts or a mitochondrion and a chloroplast The biological benefits of gene transfer remain unclear Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 7-82 The Endosymbiosis Theory

88. There are a few rare cases where infectious particles establish a symbiotic relationship with their host These have provided interesting and even bizarre examples of extranuclear inheritance Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 7-83 Symbiotic Infective Particles

89. One such example is the killer trait in the protozoan Paramecia aurelia Killer paramecia contain kappa particles in their cytoplasm Kappa particles have their own DNA which contains A gene that encodes the toxin paramecin, which kills other paramecia Genes that provide the killer paramecia with resistance to paramecin Kappa particles are infectious They can infect nonkiller strains and convert them into killer strains Infective particles have also been identified in Drosophila melanogaster Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 7-84 Symbiotic Infective Particles