Lecture 4Non-Mendelian Inheritance Part II.pdf

Non-Mendelian Inheritance Part II 5.4 Extranuclear Inheritance 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 The...

Non-Mendelian Inheritance Part II 5.4 Extranuclear Inheritance 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 2 Genetic Material of Mitochondria and Chloroplasts 1 The genetic material of mitochondria and chloroplasts is located in a region called the nucleoid The genome is composed of a single circular chromosome containing double-stranded DNA (a): From: Prachar J., “Mouse and human mitochondrial nucleoid– (b): Biophoto Associates/Science Source detailed structure in relation to function,” Gen Physiol Biophys. 2010 Jun, 29(2):160–174. Fig 3A; (a) Mitochondrion (b) Chloroplast Access the text alternative for slide images. 3 Genetic Material of Mitochondria and Chloroplasts 2 Note: A nucleoid can contain several copies of the chromosome An organelle can contain more than one nucleoid Chloroplasts tend to have more nucleoids per organelle than mitochondria TABLE 5.3 Genetic Composition of Mitochondria and Chloroplasts Organism(s) Organelle Nucleoids per Number of Chromosomes per Organelle Nucleoid Tetrahymena Mitochondrion 1 6 to 8 Mouse Mitochondrion 1 to 3 2 to 6 Chlamydomonas Chloroplast 5 to 6 ∽15 Euglena Chloroplast 20 to 34 10 to 15 Flowering plants Chloroplast 12 to 25 3 to 5 Source: Gillham, Nicholas W., Organelle Genes and Genomes. New York, NY: Oxford University Press, 1994. 4 Sizes of Organellar Genomes 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 and protists Fairly large in plants 5 Mitochondrial DNA 1 The main function of mitochondria is oxidative phosphorylation A process used to generate ATP (adenosine triphosphate), the energy source to drive cellular reactions ◦ Oxygen is consumed during ATP synthesis The human mitochondrial DNA (mtDNA) consists of only 17,000 bp (Figure 5.13) rRNA and tRNA genes 13 polypeptides 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 6 A genetic map of human mitochondrial DNA (mtDNA) Access the text alternative for slide images. 7  Chloroplast DNA 1 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 polypeptides that are required for photosynthesis Note - As with mitochondria, many chloroplast proteins are coded by genes in the nucleus These proteins contain chloroplast-targeting signals that direct them from the cytoplasm into the chloroplast 8 Maternal inheritance 1 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) 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 9 Maternal inheritance in the four-o’clock plant, Mirabilis jalapa Access the text alternative for slide images. 10 Maternal inheritance 2 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 11 Maternal inheritance 3 White phenotype is the mutant ◦ Due to a mutation that prevents the synthesis of the green pigment Variegated phenotype ◦ A cell can contain both types of chloroplasts ◦ This condition termed heteroplasmy 12 Cellular Explanation - Variegated Phenotype Consider a fertilized egg that inherited two types of chloroplasts 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 13 A cellular explanation of the variegated phenotype in Mirabilis jalapa. Access the text alternative for slide images. 14 The Pattern of Inheritance of Organelles 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 to the zygote ◦ Male gamete → Small ◦ Provides little more than a nucleus ◦ In these species, organelles are typically (but not always) inherited from the female parent ◦ Table 5.4 describes various inheritance patterns 15 Table 5.4 Transmission of Organelles Among Different Organism Organism Organelle Transmission S. Cerevisiae (Yeast) Mitochondria Biparental inheritance Molds Mitochondria Usually maternal inheritance; paternal inheritance has been found in the genus Allomyces Chlamydomonas (Alga) Mitochondria Chlamydomonas exists in two mating types (mt+ and mt−). Inherited from the parent with the mt- mating type Chlamydomonas Chloroplasts Inherited from the parent with the mt+ mating In this table mt+, mt− should be read as mt superscripttype plus and mt superscript minus Angiosperms (Plants) Mitochondria and chloroplasts Often maternal inheritance, although biparental inheritance is among some species Gymnosperms (Plants) Mitochondria and chloroplasts Usually paternal inheritance Mammals Mitochondria Maternal inheritance 16 Cellular mechanisms of maternal inheritance of mitochondria in animals 1 There are three mechanisms responsible for maternal inheritance 1. Lack of Entry of Sperm Mitochondria ◦ Sperm mitochondria do not enter the cytoplasm of the egg (ex. Chinese hamsters (Cricetulus griseus)) 2. Destruction of Sperm Mitochondrial DNA Prior to Fertilization ◦ Mitochondrial DNA is cleaved and destroyed by an endonuclease during sperm maturation (ex. Drosophila) 3. Destruction of Sperm Mitochondria After Fertilization ◦ Paternal mitochondria that enter the egg are modified by ubiquitin, a small regulatory protein that targets organelle destruction ◦ Occurs in most mammals including humans 17 Cellular mechanisms of maternal inheritance of mitochondria in animals 2 Access the text alternative for slide images. 18 Human Mitochondrial Diseases 1 Occurs in two ways Human mtDNA is transmitted from the female parent to offspring via the cytoplasm of the egg ◦ Therefore, the transmission of human mitochondrial diseases follows a strict maternal inheritance pattern Mitochondrial mutations may occur in somatic cells ◦ Accumulate as a person ages ◦ Mitochondria are very susceptible to DNA damage ◦ High oxygen consumption leads to free radicals ◦ Mitochondrial DNA has very limited repair abilities Over 200 human mitochondrial diseases have been identified These are typically chronic degenerative disorders affecting cells requiring high levels of ATP such as nerve and muscle cells 19 Table 5.5 Examples of Human Mitochondrial Diseases Disease Mitochondrial Gene Mutated Leber hereditary optic neuropathy A mutation in one of several mitochondrial genes that encode respiratory chain proteins: ND1, ND2, CO1, ND4, ND5, ND6, and cytb; tends to affect males more than females Neurogenic muscle weakness A mutation in the ATPase6 gene that encodes a subunit of the mitochondrial ATP-synthase, which is required for ATP synthesis Mitochondrial myopathy A mutation in a gene that encodes a tRNA for leucine Maternal myopathy and A mutation in a gene that encodes a tRNA for cardiomyopathy leucine 20 Heteroplasmy in Mitochondrial Disease Heteroplasmy is an important factor in mitochondrial disease Cells can contain a mixed population of mitochondria Some may carry disease causing mutation while others do not ◦ As cells divide some cells may receive a high ratio of mutant to normal mitochondria ◦ Disease may occur when the ratio of mutant to normal mitochondria exceeds a threshold value ◦ Symptoms may vary widely within a given family 21 Three Parent Babies 1 New reproductive technology emerged from the common occurrence of mitochondrial diseases ◦ Pioneered by John Zhang and colleagues (2016) in the case of a female who wanted to conceive more children but possessed a mutation in a mitochondrial gene that can cause Leigh syndrome in offspring. ◦ Using the three parent, a baby was conceived with genetic contributions of three individuals, coining the name of the method, three parent babies. 22 The Endosymbiosis Theory 1 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 23  The Endosymbiosis Theory 3 The endosymbiotic relationship provided eukaryotic cells with useful characteristics Chloroplasts gave cells the ability to carry out photosynthesis Mitochondria allowed cells to synthesize more ATP Less clear how the cyanobacteria or purple bacteria benefitted – possibly by a stable environment with an adequate supply of nutrients within the eukaryotic cell 24 The endosymbiotic origin of chloroplasts and mitochondria Access the text alternative for slide images. 25