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Non-Mendelian Inheritance

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Presentation on theme: "Non-Mendelian Inheritance"— Presentation transcript:

1 Non-Mendelian Inheritance
Mitochondria Chloroplasts Examples of non-Mendelian inheritance Human mtDNA defects Other forms of non-Mendelian Inheritance: Infectious cytoplasmic inheritance Maternal effect Genomic (parental) imprinting

2 Extranuclear Genomes:
Mitochondria (animals and plants) Chloroplasts (plants) Mitochondria and chloroplasts occur outside the nucleus, in the cytoplasm of the cell. Contain genomes (mtDNA/cpDNA) and genes, i.e., extrachromosomal genes, cytoplasmic genes, organelle genes, or extranuclear genes. Inheritance is non-Mendelian (e.g., cytoplasm typically is inherited from the mother).

3 Origin of mitochondria and chloroplasts:
Both mitochondria and chloroplasts are believed to be derived from: Endosymbiotic bacteria = free-living prokaryotes that invaded ancestral eukaryotic cells and established a mutually beneficial relationship. Mitochondria - derived from a photosynthetic purple bacterium that entered a eukaryotic cell >billion years ago. Chloroplasts - derived from a photosynthetic cyanobacterium.

4 Organization of the mtDNA genome:
mtDNAs occur in all aerobic eukaryotic cells and generate energy for cell function by oxidative phosphorylation (producing ATP). Most mtDNA genomes are circular and supercoiled (linear mtDNAs occur in some protozoa and some fungi). In some species %GC is high, allowing easy separation of pure mtDNA from nuclear DNA by gradient centrifugation. mtDNAs lack histone-like proteins (like bacteria). Copy number is high, multiple genomes per mitochondria and many mitochondria per cell (makes mtDNA easy to isolate and PCR). Size of mtDNA varies widely. Humans and other vertebrates ~16 kb (all of the mtDNA codes gene products) Yeast ~80 kb Plants ~100 kb to 2 Mb (lots of non-coding mtDNA)

5 Replication of the mtDNA genome:
Replication is semi-conservative (like nuclear DNA replication) and uses DNA polymerases specific to the mitochondria. Occurs throughout the cell-cycle (not just S phase). Control region (non-coding) forms a displacement loop (d-loop) that functions in mtDNA replication. Mitochondria (organelle) are not synthesized de novo, but grow and divide like other cells (e.g., mitosis).

6 Fig. 23.3, mtDNA replication

7 Contents of the mtDNA genome:
mtDNA contains genes for: tRNAs rRNAs cytochrome oxidase, NADH-dehydrogenase, & ATPase subunits. mtDNA genes occur on both strands. Functions of all human mtDNA ORFs are assigned. Mitochondria’s genetic information also occurs in the nuclear DNA: DNA polymerase, replication factors RNA polymerase, transcription factors ribosomal proteins, translation factors, aa-tRNA synthetase Additional cytochrome oxidase, NADH, ATPase subunits. Most required mitochondrial (and chloroplast) proteins are coded by nuclear genes in the nuclear genome. Copies of the true mtDNA genes can be transposed to the nucleus (a distinct set of genes from above): numtDNA = nuclear mtDNA

8 Fig. 23.4, Physical map of the human mtDNA

9 Transcription of the mtDNA genome:
mRNAs from the mtDNA are synthesized and translated in the mitochondria. Gene products encoded by nuclear genes are transported from the cytoplasm to the mitochondria. Mammalian and other vertebrate mtDNAs are transcribed as a single large RNA molecule (polycistronic) and cleaved to produce mRNAs, tRNAs, and rRNAs before they are processed. Most mtDNA genes are separated by tRNAs that signal transcription termination. In plants and yeast (mtDNA is much larger): tRNAs do not separate genes Gaps between genes are large Transcription is signaled by non-tRNA sequences Introns occur (do not occur in animal mtDNA) Some lack a complete stop codon (3’ end is U or UA; poly (A) tail completes the stop codon) Transcription is monocistronic

10 Translation of the mtDNA genome:
Mitochondria mRNAs do not have a 5’ cap (yeast and plant mt mRNAs have a leader). Specialized mtDNA-specific initiation factors (IFs), elongation factors (EFs), and release factors (RFs) are used for translation. AUG is the start codon (binds with fMet-tRNA like bacteria). Only plants use the “universal” genetic code. Codes for mammals, birds, and other organisms differ slightly. Extended wobble also occurs in tRNA-mRNA base-pairing (22 tRNAs are sufficient rather than 32 tRNA needed for standard wobble).

11 Useful applications of mtDNA:
Easy to isolate and PCR (high copy #). Most mtDNA is inherited maternally. Can be used to assess maternal population structure (to the exclusion of male-mediated gene flow) Because it is “haploid” effective population size of mtDNA is 1/4 that of a nuclear gene. As a result, mtDNA substitutions fix rapidly (due to genetic drift) and typically show higher levels of polymorphism. Useful for: Maternity analysis Phylogenetic systematics Population genetics (and conservation genetics) Forensics (maternal ID)



14 Chloroplast genomes (cpDNA):
Chloroplast organelles are the site of photosynthesis and occur only in green plants and photosynthetic protists, Like mtDNA, chloroplast genome is: Circular, double-stranded Lacks structural proteins %GC content differs Chloroplast genome is much larger than animal mtDNA, ~ kb. Chloroplast genomes occur in multiple copies and carry lots of non-coding DNA. Complete chloroplast sequences have been determined for several organisms (tobacco 155,844 bp; rice 134,525 bp).

15 cpDNA organization: Nuclear genome encodes some chloroplast components, and cpDNA codes the rest, including: 2 copies of each chloroplast rRNA (16S, 23S, 4.5s, 5S) tRNAs (30 in tobacco and rice, 32 in liverwort) 100 highly conserved ORFs (~60 code for proteins required for transcription, translation, and photosynthesis). Genes are coded on both strands (like mtDNA). cpDNA translation- similar to prokaryotes: Initiation uses fMet-tRNA. Chloroplast specific IFs, EFs, and RFs. Universal genetic code.

16 Fig. 23.7 cpDNA of rice

17 Rules of non-Mendelian inheritance for mtDNA and cpDNA:
Ratios typical of Mendelian segregation do not occur because meiotic segregation is not involved. Reciprocal crosses usually show uniparental inheritance because zygotes typically receive cytoplasm only from the mother. Genotype and phenotype of offspring is same as mother. Paternal leakage occurs at low levels and usually is transient; mechanisms that degrade paternal mtDNA/cpDNA exist. Heteroplasmy (mixture of mtDNA/cpDNA organelles with different DNA substitutions) results in rare cases.


19 Examples of non-Mendelian inheritance:
Variegated-shoot phenotypes in four o’clocks Mixed chloroplasts White/green Mutant chloroplast White non-photosynthetic Normal chloroplast Green photosynthetic Fig. 23.8b

20 Fig. 23.9 Chloroplasts are inherited via the seed cytoplasm 3 types of eggs (female): Normal Mutant Mixed Assumption: Pollen (male) contributes no information

21 Examples of non-Mendelian inheritance:
Mutant [poky] Neurospora possess altered mtDNA cytochrome complements that lead to slow growth. [poky] phenotype is inherited with the cytoplasm. protoperitheca (sexual mating type) conidia (asexual mating type) Fig , Reciprocal crosses of poky and wild-type Neurospora.

22 Examples of maternally inherited human mtDNA defects:
Leber’s hereditary optic neuropathy (LHON), OMIM Mid-life adult blindness from optic nerve degeneration. Mutations in ND1, ND2, ND4, ND5, ND6, cyt b, CO I, CO II, and ATPase 6 inhibit electron transport chain. Kearns-Sayre Syndrome, OMIM Paralysis of eye muscles, accumulation of pigment and degeneration of the retina, and heart disease. Deletion of mtDNA tRNAs. Myoclonic epilepsy & ragged-red fiber disease (MERRF), OMIM Spasms and abnormal tissues, accumulation of lactic acid in the blood, and uncoordinated movement. Nucleotide substitution in the mtDNA lysine tRNA. Most individuals with mtDNA disorders possess a mix of normal and mutant mtDNA, therefore severity of diseases varies depending on the level of normal mtDNA.

23 Exceptions to maternal inheritance:
Heteroplasmy, mice show paternal DNA present at 1/10,000 the level of maternal DNA. Occurs when mtDNA from sperm leak into egg cytoplasm at the time of fertilization. In these cases, maternal and paternal mtDNA can recombine! Paternal inheritance of chloroplasts commonly occurs in some plants (e.g., gymnosperms).

24 Maternal effect: Some maternal phenotypes are produced by the nuclear genome rather than the mtDNA/cpDNA genomes. Proteins or mRNA (maternal factors) deposited in the oocyte prior to fertilization; these are important for development. Genes for maternal factors occur on nuclear chromosomes; no mtDNA is involved (not epigenetic). e.g., shell coiling in the snail Limnaea peregra. Determined by a pair of nuclear alleles; D produces dextral (right-handed) coiling, d produces sinistral (left-handed) coiling. Shell coiling always is determined by the maternal genotype, not the alleles that the progeny carry or maternal phenotype. If coiling were controlled by extranuclear gene (e.g., mtDNA), progeny would always have the same phenotype as mother. Cause-female snail deposits products in the egg that regulate orientation of mitotic spindle and direction of cell cleavage.

25 Fig dextral sinistral *****dextral ***** *****dextral *****

26 Maternal effect: mRNAs coded by maternal genes (not offspring) are essential for normal structural development and axis orientation. Placement of bicoid mRNA determines anterior end of developing Drosophila embryo.

27 Genomic (parental) imprinting:
Expression of genes (or alleles) is determined by whether the gene is inherited from the father or mother. Results in expression of single allele (either from father or mother); other allele frequently suppressed by methylation. Mechanisms differ between maternal effect and imprinting: Maternal effect: dextral/sinistral coiling of snail shells. Genomic imprinting: genes from one sex suppressed by methylation (Prader-Willi syndrome, OMIM ).

28 Transovarial disease transmission - a type of maternal inheritance:
Infected cytoplasm infects the egg and is transmitted to offspring. Many insect-vectored diseases show transovarial transmission. Example - eggs and larvae of mosquitoes infected with West Nile Virus also are infected.

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