the chromosomes of organelles outside the nucleus exhibit non- mendelian patterns of inheritance
TRANSCRIPT
The Chromosomes of The Chromosomes of Organelles Outside the Organelles Outside the Nucleus Exhibit Non-Nucleus Exhibit Non-Mendelian Patterns of Mendelian Patterns of
InheritanceInheritance
Outline of Chapter 15Outline of Chapter 15
The structure and function of The structure and function of mitochondrial and chloroplast genomes, mitochondrial and chloroplast genomes, including a description of their size, including a description of their size, shape replication, and expressionshape replication, and expression
How genetic transmission revealed and How genetic transmission revealed and explained non-Mendelian patterns of explained non-Mendelian patterns of inheritanceinheritance
A comprehensive example of mutations A comprehensive example of mutations in mitochondrial DNA that affect human in mitochondrial DNA that affect human healthhealth
Mitochondrial and chloroplasts are organelles of Mitochondrial and chloroplasts are organelles of energy conversion that carry their own DNAenergy conversion that carry their own DNA
Chloroplasts – capture solar energy and Chloroplasts – capture solar energy and store it in carbohydratesstore it in carbohydrates
Mitochondria – release energy from Mitochondria – release energy from nutrients and convert it to ATPnutrients and convert it to ATP
Mitochondria are sites of the Krebs cycle and an Mitochondria are sites of the Krebs cycle and an electron transport chain that carries out the electron transport chain that carries out the
oxidative phophorylation of ADP to ATPoxidative phophorylation of ADP to ATP
Fig 15.2
Two stages by which mitochondria Two stages by which mitochondria convert food to energyconvert food to energy
Krebs cycleKrebs cycle Metabolize pyruvate and fatty acidsMetabolize pyruvate and fatty acids Produce high-energy electron carriers NADH and Produce high-energy electron carriers NADH and
FADHFADH22
Oxydative phosphorylationOxydative phosphorylation Reactions that create ATPReactions that create ATP Molecular complexes I, II, III, IV form a chain that Molecular complexes I, II, III, IV form a chain that
transports electrons from NADH and FADHtransports electrons from NADH and FADH22 to the to the final electron acceptor, oxygenfinal electron acceptor, oxygen
Complex V uses the energy released by the electron Complex V uses the energy released by the electron transport chain to form ATPtransport chain to form ATP
Chloroplasts are sites of Chloroplasts are sites of photosynthesisphotosynthesis
Capture, Capture, conversion, conversion, and storage of and storage of solar energy in solar energy in bonds of bonds of carbohydratescarbohydrates
Fig. 15.3
Photosynthesis takes place in two Photosynthesis takes place in two partsparts
Light trapping phaseLight trapping phase Solar energy is trapped and boosts electrons in Solar energy is trapped and boosts electrons in
chlorophyllchlorophyll Electrons are conveyed to electron transport systeme to Electrons are conveyed to electron transport systeme to
convert water to oxygen and Hconvert water to oxygen and H++
Electron transport forms NADPH and drives synthsis Electron transport forms NADPH and drives synthsis of ATPof ATP
Sugar-building phaseSugar-building phase Calvin cycle enzymes use ATP and NADPH to fix Calvin cycle enzymes use ATP and NADPH to fix
atmospheric carbon dioxide into carbohydratesatmospheric carbon dioxide into carbohydrates Energy is stored in carbohydrate bondsEnergy is stored in carbohydrate bonds
The genomes of mitochondriaThe genomes of mitochondria
LocationLocation mtDNA lies within matrix of the organelle in mtDNA lies within matrix of the organelle in
structures called nucleoidsstructures called nucleoids mtDNA of most cells does not reside in single mtDNA of most cells does not reside in single
locationlocation
The size and gene content of mtDNA The size and gene content of mtDNA vary from organism to organismvary from organism to organism
Unusually organized mtDNAs of Unusually organized mtDNAs of Trypanosoma, Leishmania, CrithidiaTrypanosoma, Leishmania, Crithidia
Protozoan parasites with single Protozoan parasites with single mitochondrial called kinetoplastmitochondrial called kinetoplast
mtDNA exists in one place within mtDNA exists in one place within kinetoplastkinetoplast
Large network of 10-25,000 minicircles 0.5 Large network of 10-25,000 minicircles 0.5 – 2.5 kb in length interlocked with 50-100 – 2.5 kb in length interlocked with 50-100 maxicircles 21-31 kb longmaxicircles 21-31 kb long Maxicircles contain most genesMaxicircles contain most genes Minicircles involved in RNA editingMinicircles involved in RNA editing
Human mtDNA carries closely Human mtDNA carries closely packed genespacked genes
16.5 kb in length, or 0.3% 16.5 kb in length, or 0.3% of total genome lengthof total genome length
Carries 37 genesCarries 37 genes 13 encode polypeptide 13 encode polypeptide
subunits that make up subunits that make up oxydative phosphorylation oxydative phosphorylation apparatusapparatus
22 tRNA genes22 tRNA genes 2 genes for large and small 2 genes for large and small
rRNAsrRNAs Compact gene Compact gene
arrangementarrangement No intronsNo introns Genes abut or slightly Genes abut or slightly
overlapoverlap
Fig. 15.5 a
The larger yeast mtDNA contains The larger yeast mtDNA contains spacers and intronsspacers and introns
Four times longer Four times longer than human and than human and other animal other animal mtDNAmtDNA Long intergenic Long intergenic
sequences called sequences called spacers separate spacers separate genes accounting genes accounting for more than half for more than half of DNAof DNA
Introns form Introns form about 25% of yeast about 25% of yeast genomegenomeFigure 15.5 b
The 186 kb mtDNA of the liverwort carries The 186 kb mtDNA of the liverwort carries many more genes than animals and fungimany more genes than animals and fungi
12 electron 12 electron transport genestransport genes
16 ribosomal 16 ribosomal protein genesprotein genes
29 genes with 29 genes with unknown unknown functionfunction
Fig. 15.5 c
Mitochondrial transcripts undergo RNA editing, a rare Mitochondrial transcripts undergo RNA editing, a rare variation on the basic theme of gene expressionvariation on the basic theme of gene expression
Discovered in trypanosomesDiscovered in trypanosomes Sequence of maxicircle DNA reveals only short, Sequence of maxicircle DNA reveals only short,
recognizable gene fragments instead of whole recognizable gene fragments instead of whole genesgenes
RNAs in kinetoplast are same short fragments and RNAs in kinetoplast are same short fragments and full length RNAsfull length RNAs
kDNA encodes a precursor for each mRNAkDNA encodes a precursor for each mRNA RNA editing – conversion of pre-mRNA to mature RNA editing – conversion of pre-mRNA to mature
mRNAmRNA Also found in mitochondria of some plants and Also found in mitochondria of some plants and
fungifungi
RNA editing in trypanosomesRNA editing in trypanosomes
Fig. 15.6
Translation in mitochondria shows Translation in mitochondria shows that the genetic code is not universalthat the genetic code is not universal
The genomes of chloroplasts: the The genomes of chloroplasts: the liverwort, liverwort, M. polymorphaM. polymorpha
Mitochondrial and Mitochondrial and chloroplast genomes chloroplast genomes require cooperation require cooperation
between organelle and between organelle and nuclear genomesnuclear genomes
Fig. 15.8
Origin and evolution of organelle Origin and evolution of organelle genomes: molecular evidencegenomes: molecular evidence
Endosymbiont theoryEndosymbiont theory 1970s, Lynn Margulis1970s, Lynn Margulis Mitochondria and chloroplasts orginated more than a billion years Mitochondria and chloroplasts orginated more than a billion years
agoago Ancient precursors of eukaryotic cells engulfed bacteria and Ancient precursors of eukaryotic cells engulfed bacteria and
established symbiotic relationshipestablished symbiotic relationship Molecular evidenceMolecular evidence
Both chloroplasts and mitochondria have own DNABoth chloroplasts and mitochondria have own DNA mtDNA and cpDNA are not organized into nucleosomes by histones, mtDNA and cpDNA are not organized into nucleosomes by histones,
similar to bacteriasimilar to bacteria Mitochondrial genomes use Mitochondrial genomes use NN-formyl methionine and tRNA-formyl methionine and tRNAfmetfmet in in
translationtranslation Inhibitors of bacterial translation have same effect on mitochondrial Inhibitors of bacterial translation have same effect on mitochondrial
translation, but not eukaryotic cytoplasmic protein synthesistranslation, but not eukaryotic cytoplasmic protein synthesis
Gene transfer occurs through an RNA Gene transfer occurs through an RNA intermediate or movement of pieces of DNAintermediate or movement of pieces of DNA
Genes transfer between organelles and the Genes transfer between organelles and the nucleusnucleus COXII geneCOXII gene
mtDNA genome in some plantsmtDNA genome in some plants Nuclear genome in other plantsNuclear genome in other plants Nuclear copy lacks intron – suggests transferred by Nuclear copy lacks intron – suggests transferred by
RNA intermediateRNA intermediate Movement among organellesMovement among organelles
Plant mtDNAs carry fragments of cpDNAPlant mtDNAs carry fragments of cpDNA Nonfunctional copies of organelle DNA are found Nonfunctional copies of organelle DNA are found
around the nuclear genomes of eukaryotesaround the nuclear genomes of eukaryotes
mtDNA has high rate of mutationmtDNA has high rate of mutation
10 times higher than nuclear DNA10 times higher than nuclear DNA Provides a tool for studying evolutionary Provides a tool for studying evolutionary
relationships among closely related relationships among closely related organismsorganisms maternal lineage of humans trace back to a few maternal lineage of humans trace back to a few
women who lived about 200,000 years agowomen who lived about 200,000 years ago
Maternal inheritance only in most speciesMaternal inheritance only in most species
Maternal Maternal inheritance of inheritance of XenopusXenopus mtDNA mtDNA Purified mtDNA Purified mtDNA
from two speciesfrom two species Hybridization only Hybridization only
to probes from same to probes from same speciesspecies
F1 hybrids retain F1 hybrids retain only mtDNA from only mtDNA from mothermother
Fig. 15.9
Maternal inheritance of specific Maternal inheritance of specific genes in cpDNAgenes in cpDNA
Interspecific crosses tracing biochemically Interspecific crosses tracing biochemically detectable species specific differences in detectable species specific differences in chloroplast proteinschloroplast proteins Isolated Rubisco proteins in tobacco plants in Isolated Rubisco proteins in tobacco plants in
which interspecific differences could be seenwhich interspecific differences could be seen Progeny of controlled crosses contained version Progeny of controlled crosses contained version
of Rubisco protein from maternal parent onlyof Rubisco protein from maternal parent only
A mutation in human mtDNA generates a A mutation in human mtDNA generates a maternally inherited neurodegenerative diseasematernally inherited neurodegenerative disease
Leber’s hereditary optic neurophathy Leber’s hereditary optic neurophathy (LHON) leads to optic nerve degeneration (LHON) leads to optic nerve degeneration and blindnessand blindness
Substitution in mtDNA at nucleotide 11,778Substitution in mtDNA at nucleotide 11,778
Fig. 15.10
Cells can contain one type or a Cells can contain one type or a mixture of organelle genomesmixture of organelle genomes
Heterplasmic – cells contain a mixture of Heterplasmic – cells contain a mixture of organelle genomesorganelle genomes Mitotic products may contain one type, a Mitotic products may contain one type, a
mixture of types, or the second typemixture of types, or the second type Homoplastic – cells contain one type of Homoplastic – cells contain one type of
organelle DNAorganelle DNA Mitotic products contain same type, except for Mitotic products contain same type, except for
rare mutationrare mutation
Mitotic segregation produces an uneven distribution of Mitotic segregation produces an uneven distribution of organelle genes in heteroplasmic cellsorganelle genes in heteroplasmic cells
Women with heteroplasmic LHON Women with heteroplasmic LHON mutationmutation Some ova may carry few mitochondria with Some ova may carry few mitochondria with
LHON mutation and large number of wild-typeLHON mutation and large number of wild-type Other ova may carry mainly mitochondrial Other ova may carry mainly mitochondrial
with LHON mutation and few wild-typewith LHON mutation and few wild-type Consequence of heteroplasmy after fertilizationConsequence of heteroplasmy after fertilization
Some cells produce tissues with normal ATP Some cells produce tissues with normal ATP production and others with low productionproduction and others with low production
If low production cells are in optic nerve, LHON If low production cells are in optic nerve, LHON resultsresults
Experiments with Experiments with mutants of cpDNA mutants of cpDNA in in Chlamydomonas Chlamydomonas reinhardtiireinhardtii reveal reveal
uniparental uniparental inheritance of inheritance of chloroplastschloroplasts
Fig. 15.11 b
A cross of A cross of C. reinhardtiiC. reinhardtii gametes illustrates lack gametes illustrates lack
of segregation of cpDNA of segregation of cpDNA at meiosisat meiosis
Fig. 15.11 c
Mechanisms of unipartental Mechanisms of unipartental inheritanceinheritance
Differences in gamete sizeDifferences in gamete size Degredation of organelles in male gametes of some Degredation of organelles in male gametes of some
organismsorganisms In some plants paternal organelle genomes are In some plants paternal organelle genomes are
distributed to cells that are destined to not become distributed to cells that are destined to not become part of the embryo during early developmentpart of the embryo during early development
In some organisms, the zygote destroys paternal In some organisms, the zygote destroys paternal organelle after fertilizationorganelle after fertilization
Other organisms, paternal organelles excluded Other organisms, paternal organelles excluded from female gametefrom female gamete
In yeast, mtDNA-encoded traits show a biparental In yeast, mtDNA-encoded traits show a biparental mode of inheritance and mitotic segregationmode of inheritance and mitotic segregation
Fig. 15.13
Recombinant DNA techniques to Recombinant DNA techniques to study genetics of organellesstudy genetics of organelles
Gene gun – biolistic Gene gun – biolistic transformationtransformation Small (1mm) metal beads Small (1mm) metal beads
with DNA are shot at with DNA are shot at cellscells
Rarely, DNA passes Rarely, DNA passes through cell wall and through cell wall and enters nucleusenters nucleus
Used to transform cellsUsed to transform cells E.g., GFP constructs can E.g., GFP constructs can
be used as selectable be used as selectable markers to identify markers to identify transformantstransformants
Fig. 15.14
How mutations in mtDNA affect How mutations in mtDNA affect human healthhuman health
Individuals with Individuals with certain rare diseases of certain rare diseases of the nervous system are the nervous system are heteroplasmicheteroplasmic MERRF, myoclonic MERRF, myoclonic
epilepsy and ragged red epilepsy and ragged red fiber diseasefiber disease
Uncontrolled jerking, Uncontrolled jerking, muscle weakness, muscle weakness, deafness, heart problems, deafness, heart problems, kidney problems, kidney problems, progressive dementiaprogressive dementia
Fig. 15.15 a
Maternal inheritance of MRRFMaternal inheritance of MRRF
Fig. 15.15 b
Proportion of Proportion of mutant mtDNA mutant mtDNA
and tissue in and tissue in which they reside which they reside
influence influence phenotypephenotype
Fig. 15.16
Mitochondrial inheritance in Mitochondrial inheritance in identical twinsidentical twins
Mitochondrial genomes not same in twins Mitochondrial genomes not same in twins but nuclear genomes are identicalbut nuclear genomes are identical Symptoms of neurodegenerative diseases or Symptoms of neurodegenerative diseases or
other mutations may manifest in one twin, but other mutations may manifest in one twin, but not othernot other
In heteroplasmic mother, chance of phenotype In heteroplasmic mother, chance of phenotype depends on both partitioning of mutant mtDNA depends on both partitioning of mutant mtDNA after fertilization, and tissue that receive after fertilization, and tissue that receive mutation during developmentmutation during development
mtDNA mutations and agingmtDNA mutations and aging
Hypothesis: Accumulation of mutations in Hypothesis: Accumulation of mutations in mtDNA over lifetime and biased replication of mtDNA over lifetime and biased replication of deleted mtDNA result in age-related decline in deleted mtDNA result in age-related decline in oxidative phosphorylationoxidative phosphorylation Evidence:Evidence:
Deleterious mtDNA mutations early in life diminish ATP Deleterious mtDNA mutations early in life diminish ATP productionproduction
Decreases in cytochrome c oxidase in hearts from autopsies Decreases in cytochrome c oxidase in hearts from autopsies (gene encoded in mtDNA)(gene encoded in mtDNA)
Rate of deletions increases with ageRate of deletions increases with age Alzheimer’s individuals have abnormally low energy Alzheimer’s individuals have abnormally low energy
metabolismmetabolism