Transcript Non-Mendelian inheritance

Non-Mendelian Inheritance
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Mitochondria
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Chloroplasts
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Examples of non-Mendelian inheritance
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Human mtDNA defects
Other forms of non-Mendelian Inheritance:
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Infectious cytoplasmic inheritance
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Maternal effect
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Genomic (parental) imprinting
Extranuclear Genomes:
Mitochondria (animals and plants)
Chloroplasts (plants)
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Mitochondria and chloroplasts occur outside the nucleus, in the
cytoplasm of the cell.
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Contain genomes (mtDNA/cpDNA) and genes, i.e.,
extrachromosomal genes, cytoplasmic genes, organelle genes, or
extranuclear genes.
3.
Inheritance is non-Mendelian (e.g., cytoplasm typically is inherited
from the mother).
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.
1.
Mitochondria - derived from a photosynthetic purple bacterium that
entered a eukaryotic cell >billion years ago.
2.
Chloroplasts - derived from a photosynthetic cyanobacterium.
Organization of the mtDNA genome:
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mtDNAs occur in all aerobic eukaryotic cells and generate energy for
cell function by oxidative phosphorylation (OXPHOS) producing ATP.
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Most mtDNA genomes are circular and supercoiled (linear mtDNAs
occur in some protozoa and some fungi).
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In some species %GC is high, allowing easy separation of pure
mtDNA from nuclear DNA by gradient centrifugation.
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mtDNAs lack histone-like proteins (like bacteria).
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Copy number is high, multiple genomes per mitochondria and many
mitochondria per cell (makes mtDNA easy to isolate and PCR).
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Size of mtDNA varies widely.
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Humans and other vertebrates
~16 kb
(all of the mtDNA codes gene products)
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Yeast
Plants
(lots of non-coding mtDNA)
~80 kb
~100 kb to 2 Mb
Replication of the mtDNA genome:
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Replication is semi-conservative (like nuclear DNA replication) and
uses DNA polymerases specific to the mitochondria.
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Occurs throughout the cell-cycle (not just S phase).
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Control region (non-coding) forms a displacement loop (d-loop) that
functions in mtDNA replication.
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Mitochondria (organelle) are not synthesized de novo, but grow and
divide like other cells (e.g., mitosis).
Fig. 23.3, mtDNA replication
Contents of the mtDNA genome:
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mtDNA contains genes for:
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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:
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DNA polymerase, replication factors
RNA polymerase, transcription factors
ribosomal proteins, translation factors, aa-tRNA synthetase
Additional cytochrome oxidase, NADH, ATPase subunits.
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Most required mitochondrial (and chloroplast) proteins are coded by
nuclear genes in the nuclear genome.
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Copies of the true mtDNA genes can be transposed to the nucleus (a
distinct set of genes from above):
numtDNA = nuclear mtDNA
Fig. 23.4, Physical map of the human mtDNA
Transcription of the mtDNA genome:
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mRNAs from the mtDNA are synthesized and translated in the
mitochondria.
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Gene products encoded by nuclear genes are transported from the
cytoplasm to the mitochondria.
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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.
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Most mtDNA genes are separated by tRNAs that signal transcription
termination.
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In plants and yeast (mtDNA is much larger):
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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
Translation of the mtDNA genome:
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Mitochondria mRNAs do not have a 5’ cap (yeast and plant mt
mRNAs have a leader).
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Specialized mtDNA-specific initiation factors (IFs), elongation
factors (EFs), and release factors (RFs) are used for translation.
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AUG is the start codon (binds with fMet-tRNA like bacteria).
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Only plants use the “universal” genetic code. Codes for mammals,
birds, and other organisms differ slightly.
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Extended wobble also occurs in tRNA-mRNA base-pairing (22 tRNAs
are sufficient rather than 32 tRNA needed for standard wobble).
Useful applications of mtDNA:
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Easy to isolate and PCR (high copy #).
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Most mtDNA is inherited maternally. Can be used to assess
maternal population structure (to the exclusion of male-mediated
gene flow)
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Because it is “haploid” effective population size of mtDNA is 1/4 that
of a nuclear gene.
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As a result, mtDNA substitutions fix rapidly (due to genetic drift)
and typically show higher levels of polymorphism and genetic
differentiation between populations.
Useful for:
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Maternity analysis
Phylogenetic systematics
Population genetics (and conservation genetics)
Forensics (maternal ID)
Chloroplast genomes (cpDNA):
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Chloroplast organelles are the site of photosynthesis and occur only
in green plants and photosynthetic protists,
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Like mtDNA, chloroplast genome is:
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Circular, double-stranded
Lacks structural proteins
%GC content differs
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Chloroplast genome is much larger than animal mtDNA, ~80-600 kb.
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Chloroplast genomes occur in multiple copies and carry lots of noncoding DNA.
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Complete chloroplast sequences have been determined for several
organisms (tobacco 155,844 bp; rice 134,525 bp).
cpDNA organization:
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Nuclear genome encodes some chloroplast components, and cpDNA
codes the rest, including:
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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:
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Initiation uses fMet-tRNA.
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Chloroplast specific IFs, EFs, and RFs.
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Universal genetic code.
Fig. 23.7
cpDNA of rice
Rules of non-Mendelian inheritance for mtDNA and cpDNA:
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Ratios typical of Mendelian segregation do not occur because
meiotic segregation is not involved.
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Reciprocal crosses usually show uniparental inheritance because
zygotes typically receive cytoplasm only from the mother.
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Genotype and phenotype of offspring is same as mother.
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Paternal leakage occurs at low levels and usually is transient;
mechanisms that degrade paternal mtDNA/cpDNA exist.
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Heteroplasmy (mixture of mtDNA/cpDNA organelles with different
DNA substitutions) results in rare cases.
http://bmj-sti.highwire.org/content/77/3/158.full
Examples of non-Mendelian inheritance:
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Variegated-shoot phenotypes in four o’clocks
Mixed chloroplasts
White/green
Mutant chloroplast
White
non-photosynthetic
Normal chloroplast
Green
photosynthetic
Fig. 23.8b
Fig. 23.9
Chloroplasts are inherited
via the seed cytoplasm
3 types of eggs (female):
Normal
Mutant
Mixed
Assumption:
Pollen (male) contributes
no information
Examples of non-Mendelian inheritance:
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Mutant [poky] Neurospora possess altered mtDNA cytochrome
complements that lead to slow growth.
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[poky] phenotype is inherited with the cytoplasm.
protoperitheca (sexual mating type)
conidia
(asexual mating type)
Fig. 23.10, Reciprocal crosses of poky and wild-type Neurospora.
Examples of maternally inherited human mtDNA defects:
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Leber’s hereditary optic neuropathy (LHON), OMIM-535000
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Kearns-Sayre Syndrome, OMIM-530000
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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.
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), OMIM545000
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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.
Exceptions to maternal inheritance:
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Heteroplasmy, mice show paternal DNA present at 1/10,000 the
level of maternal DNA.
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Occurs when mtDNA from sperm leak into egg cytoplasm at the time
of fertilization.
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In these cases, maternal and paternal mtDNA can recombine!
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Paternal inheritance of chloroplasts commonly occurs in some plants
(e.g., gymnosperms).
www.sciencemusings.com/
Maternal effect:
Some maternal phenotypes are produced by the nuclear genome rather
than the mtDNA/cpDNA genomes.
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Proteins or mRNA (maternal factors) deposited in the oocyte prior
to fertilization; these are important for development.
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Genes for maternal factors occur on nuclear chromosomes; no
mtDNA is involved (not epigenetic).
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e.g., shell coiling in the snail Limnaea peregra.
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Determined by a pair of nuclear alleles; D produces dextral
(right-handed) coiling, d produces sinistral (left-handed)
coiling.
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Shell coiling always is determined by the maternal genotype,
not the alleles that the progeny carry or maternal phenotype.
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If coiling were controlled by extranuclear gene (e.g., mtDNA),
progeny would always have the same phenotype as mother.
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Cause-female snail deposits products in the egg that regulate
orientation of mitotic spindle and direction of cell cleavage.
Fig. 23.17
dextral
sinistral
*****dextral *****
*****dextral *****
Maternal effect:
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mRNAs coded by maternal genes (not offspring) are essential for
normal structural development and axis orientation.
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Placement of bicoid mRNA determines anterior end of developing
Drosophila embryo.
http://scienceblogs.com/pharyngula/2006/06/maternal_effect_genes.php
Genomic (parental) imprinting:
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Expression of genes (or alleles) is determined by whether the gene
is inherited from the father or mother.
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Results in expression of single allele (either from father or mother).
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Mechanism is entirely different from maternal effect (e.g.,
dextral/sinistral coiling of snail shells).
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One allele frequently suppressed by methylation.
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Prader-Willi syndrome, OMIM-176270
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Common in various cancers
Transovarial disease transmission - a type of maternal inheritance:
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Infected cytoplasm infects the egg and is transmitted to offspring.
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Many insect-vectored diseases show transovarial transmission.
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Example - eggs and larvae of mosquitoes infected with West Nile
Virus also are infected.
http://gsbs.utmb.edu/microbook/ch056.htm