Presentation on theme: "Mitochondrial Genomes and Mutations MUPGRET Workshop June 21, 2005 K. Newton presenter."— Presentation transcript:
Mitochondrial Genomes and Mutations MUPGRET Workshop June 21, 2005 K. Newton presenter
Organelle Genetics Terms are not necessarily equivalent! Maternal inheritance Non-Mendelian inheritance –Ratios do not fit those proposed by Mendel Cytoplasmic inheritance Nonchromosomal inheritance Plasmon = genetic elements of the cytoplasm e.g. homoplasmic, heteroplasmic
Examples of non-Mendelian inheritance: Variegated-shoot phenotypes in four o’clocks (Correns, 1908) Normal chloroplast Green photosynthetic Mutant chloroplast White non-photosynthetic Mixed chloroplasts White/green
Maternal inheritance Experiments were performed by Correns on the four o'clock plant Green, variegated (white and green) or white leaves Normal flowers develop at different locations on the plant Crosses were made among the flowers associated with: Female Male Phenotype Progeny Phenotype Phenotype Green Green, variegated or white Green Variegated Green, variegated or white Variegated White Green, variegated or white White The progeny cross always exhibited the color of the leaf of the female Trait expresses maternal inheritance Animals and most plants, including corn, Arabidopsis, wheat and tomato show strict maternal inheritance of organellar (chloroplast and mitochondrial) DNA. The female phenotype in a cross is always expressed in its offspring
In plants, sometimes observe biparental inheritance Inheritance of variegation suggesting both parents contribute, but ratios are non-Mendelian. Male (pollen) transmission of chloroplasts plastids found for several plant species –e.g. Pelargonium (geranium), Oenothera, Medicago, Phaseolus, Acacia Some plants have regular paternal transmission of plastids through pollen.
Origins of mitochondria & chloroplasts Both mitochondria and chloroplasts are believed to be derived from endosymbiotic bacteria. Endosymbiotic bacteria = free-living prokaryotes that invaded ancestral eukaryotic cells and established a mutually beneficial relationship. Mitochondria - believed to be derived from a photosynthetic purple bacterium that entered a eukaryotic cell > billion years ago. Chloroplasts - believed to be derived from a photosynthetic cyanobacterium. Many required mitochondria and chloroplast proteins also are coded by nuclear genes. numtDNA = nuclear mtDNA (mtDNA transposed to the nucleus)
mtDNAs --- Overview mtDNAs occur in (almost) all aerobic eukaryotic cells & generate energy for cells by oxidative phosphorylation (producing ATP). Most mtDNA genomes are circular and supercoiled (linear mtDNAs occur in some protozoa and some fungi). mtDNAs lack histone-like proteins. Copy number is high, multiple genomes per mitochondria and many mitochondria per cell (can easily PCR). Sizes of mtDNA varies widely. Humans and other vertebrates~17 kb (all of mtDNA codes gene products) Yeast~80 kb Plants~100 kb to 2 Mb (lots of non-coding mtDNA)
Plant mitochondrial genomes are large & variable in size Photo: D. Stern and K. Newton
37 genes Griffiths et al. Genetic Analysis 7th edition
Maize mitochondrial genome ~ 570 kb 58 identified genes 33 known proteins 21 tRNAs (for 14 diff aa)* 3 rRNAs * A tRNA is carried on a 2 kb linear plasmid From Clifton et al. 2004, Plant Physiology
What is in the NB maize mitochondrial genome ? Based on genome complexity (one copy of large repeats removed) 520 kb for maize NB 359 kb for rice Exons Introns rRNAs ctDNA tRNAs ??? ORFs pseudo From Clifton et al. 2004, Plant Physiology
Louis with inbred corn Louis with hybrid corn Mitochondrial DNA mutations can help in the production of hybrid corn!
CMS = cytoplasmic male sterility is a trait carried by mitochondrial DNA Rf = Restorer of fertility gene--from nucleus which causes an override of mitochondrially-determined sterility Drawn by K.T. Yamato
The molecular basis of cytoplasmic male sterility and fertility restoration. P.S. Schnable & R.P. Wise Trends in Genetics 1998 5’ 3’ rrn26 3’ flank ? rrn26 88918 amino acids maize T-urf13 (Dewey et al. Cell 44:439) Promoter is a strong promoter From the atp6 gene Cytoplasmic Male Sterility One type of mitochondrial mutation in plants--chimeric genes Defect is stage specific.
Petunia CMS atp9 ? cox2 exon1 cox2 exon2 urfS 3546989157amino acids 5’ 3’ petunia S-pcf (Young and Hanson Cell 50:41) Normal petunia with abundant pollen Flower from CMS petunia: no pollen produced
Human Mitochondrial Genomes Human Nuclear Genome: About 30,000 genes on 23 chromosomes (3.3 billion base pairs/haploid cell) Mitochondrial Genome contains 37 genes: –13 code for some of the proteins involved in oxidative respiration –22 tRNA genes –2 rRNA genes –16,569 base pairs, circular, very compact, filled with genes
Mitochondrial Inheritance. As mitochondria are inherited almost exclusively from the mother, defects in mtDNA will be passed on from the mother to her children, as illustrated in this pedigree. Maternal Inheritance of mtDNA defects
Human Mitochondrial DNA Mutations Are maternally inherited: only offspring of affected mothers are affected Show deficiency in mitochondrial function Are caused by a mutation in a mitochondrial gene Examples: myoclonic epilepsy and ragged red fiber disease (MERRF) Deafness, dementia, seizures Point Mutation in a mitochondrial tRNA Leber’s Hereditary Optic Neuropathy (LHON) Sudden bilateral blindness Point mutation in small subunit of Complex I of the ETC Kearns-Sayre Syndrome (KSS) Symptoms in eyes, muscles, heart, brain Deletion mutation in mtDNA
DiMauro et al. 1998 BBA 199-210. As shown in Griffiths et al. Genetic Analysis 7th edition
http://www.mitoresearch.org/treatmentdisease.html Commonly Affected Systems in Mitochondrial Disorders
Figure from: Griffiths et al. Genetic Analysis, 7th edition Subunits of complexes in the mitochondrial electron transfer chain are encoded by both nuclear and mitochondrial DNA Note: This is for human mtDNA. Plant mtDNAs code for a few extra subunits Mutations in the nuclear genes coding for subunits of the mitochondrial ETC complexes are usually inherited as Mendelian recessive traits
If mitochondrial function is so important, why aren’t all of the defective mitochondrial DNA mutations lethal? Heteroplasmy
HETEROPLASMY: Normal mitochondria with normal DNA vs Mitochondria with mutant DNA "Homoplasmic Cell. Healthy people have homoplasmic cells -- that is, each cell has normal mitochondrial DNA. People with mitochondrial DNA mutations have heteroplasmic cells. Each cell has a mixture of good and bad mitochondria. 70% mutant mitochondria = severe symptoms 30% mutant mitochondria = mild symptoms Heteroplasmic Cells Homoplasmic Cell http://www.mitoresearch.org/mitodiseases.html
Variable “penetrance” of mitochondrial disease corrrelates With the amount of mutant mtDNA
From the following article: Premature ageing in mice expressing defective mitochondrial DNA polymerase Aleksandra Trifunovic, Anna Wredenberg, Maria Falkenberg, Johannes N. Spelbrink, Anja T. Rovio, Carl E. Bruder, Mohammad Bohlooly-Y, Sebastian Gidlöf, Anders Oldfors, Rolf Wibom, Jan Törnell, Howard T. Jacobs and Nils-Göran LarssonNature 429, 417-423 (27 May 2004) Premature ageing in mice expressing defective mitochondrial DNA polymerase Premature aging in mice carrying mtDNA mutations
Heteroplasmy & Mitochondrial Defects in Corn Deletions in in essential mitochondrial genes (Newton lab focus) Reduced height Striped (sectored) leaves Sectors of aborted kernels NCS Normal
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