BMS 532 Mitochondrial Genetics and Heredity PDF

Mitochondrial Genetics BMS 532 MOLECUL AR BIOLOGY AND GENETICS BLOCK 3 LECTURE 6 Objectives 1. Define the following terms: nucleoid, variable expression/variable patterns, parental leakage, and heteroplasmy 2. Explain the size and susceptibility to damage of the mitochondrial genome 3. Explain h...

Mitochondrial Genetics BMS 532 MOLECUL AR BIOLOGY AND GENETICS BLOCK 3 LECTURE 6 Objectives 1. Define the following terms: nucleoid, variable expression/variable patterns, parental leakage, and heteroplasmy 2. Explain the size and susceptibility to damage of the mitochondrial genome 3. Explain how inheritance of mitochondria differs from autosomal or sex- linked inheritance 4. List the different options for mitochondrial inheritance 5. Explain the role of mitochondrial DNA in human disease 6. Assess the inheritance of mitochondrial genomes based on the expected inheritance patterns and parental expression of the mitochondria LO1, LO2 Mitochondrial Genome (mtDNA) Circular genome (~16,500 base pairs) mtDNA is arranged with proteins into complexes = Nucleoids ◦ Contains all of the information for propagation, transcription, stabilization of the genome, and the small amount of repair they can perform ◦ Very limited repair abilities with high susceptibility to mutation (repair has evolved to deal with ROS but still limited) ◦ Mutations can occur in somatic cells and be propagated within a tissue causing accumulation of the altered mitochondria with aging Chinnery and Hudson LO1, LO3 More Mitochondrial Genetics Transcription and translation are possible within the mitochondria and resemble prokaryotic processes including polycistronic mRNA Variants of mitochondrial genomes have been identified via resequencing analyses Most humans actually contain multiple mitochondrial genotypes with specific patterns of variants accumulating in different tissues over time Mitotic events and the equal division of the cytoplasm mean that it is possible for a cell expressing multiple mitochondria to have offspring inheriting variable patterns of the mitochondria LO1, LO2, LO3, LO4 Mitochondrial Inheritance Most of the cytoplasm and therefore cytoplasmic material is contained within the oocyte thus mitochondria and their genomes are most often maternally inherited ◦ NOTE: Chloroplast inheritance is similar Inheritance patterns can vary among species ◦ Mammals = maternal inheritance ◦ Yeast (i.e. S. cerevisiae) = Biparental inheritance ◦ Plants (mitochondria AND chloroplasts) ◦ Angiosperms = most often maternal though biparental is possible ◦ Gymnosperms = usually paternal inheritance MOST offspring do NOT inherit any paternal mitochondria when maternal inheritance is expected Parental Leakage refers to the occasional inheritance of mitochondria via sperm when maternal inheritance is typical ◦ Mouse example = 1 to 4 per 100,000 mitochondria are inherited via paternal means LO1, LO2, LO3, LO5 Mitochondrial Inheritance Cannot use traditional Punnett squares to evaluate inheritance Must consider: 1) mode of inheritance (Maternal? Paternal? Biparetal?) 2) whether parent of origin has the ability to express more than one type ◦ Heteroplasmy = expressing mutations alongside normal counterparts ◦ More than one type of mitochondria present ◦ Variable proportions of mutant and wildtype versions are possible Also must consider the genotype to phenotype ratio Knorre 2019 LO1, LO2, LO3 Mitochondrial Inheritance In situations where more than one type of mitochondrion is observed, the inheritance of the mitochondria is more varied ◦ Example: If a plant has more than one chloroplast (one for green and one for white) and exhibits a mixed phenotype (both green and white) in their leaves ◦ the offspring could have white leaves, green leaves, or the mixture observed in the parent ◦ Tying this to mitochondria, if two types of mitochondria are present in the maternal parent ◦ the offspring could inherit one, the other, or both ◦ NOTE: some evidence in humans implicates familial specific biparental inheritance in humans (Luo et al 2018) though it could also be considered this variable inheritance from a maternal source with more than one mtDNA option LO1, LO5 Mitochondrial Disease and Inheritance There is a wide range of consequences and significant implications for mtDNA in human health Multiple tissues and organs can be affected by altered mitochondrial function ◦ Somatic mutations can lead to tissue specific consequences over time The complex inheritance patterns mean that there are different considerations for mtDNA disorders ◦ Maternal inheritance complicates female fertility for individuals with mitochondrial disorders Chinnery and Hudson LO6 Determining Inheritance Two individuals of a species have offspring. The maternal individual is heteroplastic while the paternal individual is homoplastic. Answer the following questions: ◦ If maternal mitochondrial inheritance is expected: ◦ What is the potential for the offspring? ◦ What is the potential for the next generation if the offspring are all female? All male? ◦ If paternal mitochondrial inheritance is expected: ◦ What is the potential for the offspring? ◦ What is the potential for the next generation if the offspring are all female? All male?