Genetics PCB 3063

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Genetics - PCB 3063

• Todays focus
• EXTRANUCLEAR INHERITANCE
• We will focus on three major questions today
• Are all genes present in the nucleus?
• How are extranuclear genes inherited?
• How do other extranuclear factors influence
  phenotype?
• In addition, we will discuss the phenomenon of
  complementation, the definition of CISTRONS, and
  process of fine-structure mapping.

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Complementation

• Multiple genes can have the same phenotype.
• E.g., there are 7 genes in S. cerevisiae that are
  necessary for the biosynthesis of lysine.
• These genes are all designated LYS.
• They are present at different chromosomal loci
  (unlinked).
• Different genes encode different enzymes.
• COMPLEMENTATION is consequence of the fact that
  different LYS genes encode different enzymes.
• Imagine a lys2 mutant - a homozygous diploid (or
  haploid) will be unable to grow without lysine
  (it is an AUXOTROPH)
• The same is true for a lys7 mutant.
• But if we mate haploid spores with the mutants,
  each gene will have one dominant (functional)
  allele - and the diploid will be able to grow
  without lysine (it is a PROTOTROPH).

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Complementation and Cistrons

• Mutations that fail to complement belong to the
  same CISTRON.
• This terminology was introduced by S. Benzer
  based upon the possible arrangements (cis or
  trans) for mutations.
• For many genes, there is a single cistron per
  gene.

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Fine Structure Mapping

• Fine-structure mapping is based upon
  recombination - just like other forms of genetic
  mapping.
• Recombination between mutations in the same gene
  can restore the wild-type phenotype.
• In some cases, different point mutations in the
  same gene will complement each other.
• For example, the book shows two different alleles
  of an arg gene (arginine auxotrophy) in which
  different point mutants can complement each
  other.
• These cases are rare, and are contrary to the
  normal method (complementation) used to determine
  whether mutations affect the same gene.
• These mutations will not complement deletion
  mutants, or point mutations that strongly alter
  function.

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Maternal Effects Genes

• Lets move away from nuclear genes.
• When gametes are made, gene products produced by
  the parents can be packaged in the gametes.

• Female gametes are substantially larger than male
  gametes.
• Therefore, there are many examples of maternal
  gene products packaged into eggs.
• This can result in distinct patterns of
  inheritance.
• For example, the A gene in this figure.
• Similar to snail example in the text.

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Shell Coiling in Snailsand Pigmentation in Flour
Moths

• Shell coiling in the pond snail Limnaea peregra.
• The direction of shell coiling (leftsinistrally
  or rightdextrally) is controlled by a single
  gene.
• Dextral coiling is dominant.
• However, the coiling of individuals actually
  reflects the genotype of the mother.
• Progeny of DD or Dd females will be dextral,
  regardless of the male parents phenotype or
  genotype.
• Progeny of dd females will be sinistral.
• Pigmentation in flour moths.

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Shell Coiling in Snailsand Pigmentation in Flour
Moths

• Shell coiling in the pond snail Limnaea peregra.
• Pigmentation in flour moths.
• This example is even more straightforward
• A single gene (a and a) controls pigmentation.
• a behaves like a normal Mendelian gene with
  respect to adult pigmentation.
• However, all progeny of pigmented females (aa
  or aa) are pigmented as larvae.
• Some pigment made by the mother is packaged in
  the egg and used to color the larvae.

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Are Maternal Effects GenesNon-Mendelian?

• The inheritance of maternal effects genes may
  seem unusual, but the pattern reflects two
  straightforward phenomena
• Expression of the trait is sex-limited.
• Sex-limited traits are distinct from sex-linked
  traits. Sex-limited traits can be controlled by
  autosomal genes -- sex-linked traits are
  controlled by genes on sex chromosomes (by
  definition).
• The sex-limited nature of the reflects the fact
  that only females make large gametes which can
  carry substantial amounts of gene products.
• Any gene that affects development of a male or
  female specific structure will necessarily be
  sex-limited.
• The female phenotype is expressed in the progeny.

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Are Maternal Effects GenesNon-Mendelian?

• The inheritance of maternal effects genes may
  seem unusual, but the pattern reflects two
  straightforward phenomena
• The expression of the trait is sex-limited.
• The female phenotype is expressed in the progeny.
• Think of the progeny as an extension of their
  mother.
• Conceptually, this would be identical to a part
  of the mother being included in the offspring.
• Logically that part of the mother would show the
  maternal phenotype.
• But some genes are actually extranuclear.

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Some Genes are Extranuclear

• Maternal effects do not reflect the inheritance
  of an extranuclear gene - only an extranuclear
  gene product
• Both MITOCHONDRIA and PLASTIDS have their own
  genomes.
• The genomes of these organelles are typically
  circular, rather than linear.
• Many gene products necessary for organelle
  function are imported from outside of the
  organelles and are encoded by nuclear genes.
• Mitochondrial (mt) genomes vary considerably in
  size and gene content
• Vertebrate mt genomes are small (16-20 kbp) and
  have few genes (13 protein coding, 2 rRNA and 22
  tRNA)
• Plant mt genomes are typically very large
  (100-400 kbp) and have a fairly large number of
  genes (Arabidopsis has 120 protein coding genes,
  3 rRNA and 21 known tRNA genes).

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Chloroplast Genes

• Chloroplast genomes are moderately sized (100-200
  kbp) and encode for some of the genes necessary
  for photosynthesis.
• Arabidopsis has 90 protein coding genes, 8 rRNA,
  and 37 tRNA genes in the chloroplast genome.
• These encode photosynthetic proteins for both the
  light- and dark-reactions of photosynthesis as
  well as genes for protein and RNA synthesis.
• In many cases proteins encoded by the chloroplast
  assemble with nuclear encoded proteins to form
  active complexes.
• Some non-photosynthetic organisms have
  chloroplasts.

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Chloroplast Genes

• Chloroplast genomes are moderately sized (100-200
  kbp) and encode for some of the genes necessary
  for photosynthesis.
• Arabidopsis has 90 protein coding genes, 8 rRNA,
  and 37 tRNA genes in the chloroplast genome.
• Some non-photosynthetic organisms have
  chloroplasts.
• These include parasitic plants that have lost the
  ability to conduct photosynthesis as well as
  apicomplexan parasites such as Plasmodium and
  Toxoplasma.
• Apicomplexan parasites have much smaller
  chloroplast genomes (35 kbp with 26 protein
  coding genes) - none of which are involved in
  photosynthesis.
• These organelles have prompted considerable
  interest as possible drug targets.

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The Endosymbiotic Origin of Eukaryotic Organelles

• Both mitochondria and chloroplasts are thought to
  have arisen from prokaryotic ancestor that were
  incorporated into eukaryotes.
• For mitochondria, a-proteobacteria were the
  ancestors.
• This lineage includes some bacteria that are
  intracellular parasites (such as Rickettsia) or
  bacterial symbionts of eukaryotes (such as
  Agrobacterium).
• Although most mitochondria are highly reduced in
  gene content, one eukaryote with a mitochondiral
  genome resembling a eubacterial genome has been
  found.
• This is a protozoan called Reclinomonas
  americana.
• For chloroplasts, cyanobacteria were the
  ancestors.

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The Endosymbiotic Origin of Eukaryotic Organelles

• Both mitochondria and chloroplasts are thought to
  have arisen from prokaryotic ancestor that were
  incorporated into eukaryotes.
• For mitochondria, a-proteobacteria were the
  ancestors.
• Although most mitochondria are highly reduced in
  gene content, one eukaryote with a mitochondiral
  genome resembling a eubacterial genome has been
  found.
• This is a protozoan called Reclinomonas
  americana.
• The Reclinomonas mt genome is 69 kbp in size and
  encodes 97 genes.
• Although it is smaller than some plant mt
  genomes, much of the larger size of plant mt
  genomes reflects duplication and non-coding DNA.
• For chloroplasts, cyanobacteria were the
  ancestors.

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The Endosymbiotic Origin of Eukaryotic Organelles

• Both mitochondria and chloroplasts are thought to
  have arisen from prokaryotic ancestor that were
  incorporated into eukaryotes.
• For mitochondria, a-proteobacteria were the
  ancestors.
• For both mitochondria and chloroplasts, an
  ancestral eukaryote is thought to have engulfed a
  prokaryote that was enslaved and became an
  obligate endosymbiont.
• Some bacterial genes were transferred to the
  nucleus but others were retained in organelle
  genomes.
• This process of organelle to nucleus gene
  transfer is ongoing
• E.g., Neurospora crassa has a functional ATPase
  subunit 9 gene in the nucleus but a homologous
  sequence remains in the mitochondrion.
• For chloroplasts, cyanobacteria were the
  ancestors.

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The Endosymbiotic Origin of Eukaryotic Organelles

• Both mitochondria and chloroplasts are thought to
  have arisen from prokaryotic ancestor that were
  incorporated into eukaryotes.
• For mitochondria, a-proteobacteria were the
  ancestors.
• For chloroplasts, cyanobacteria were the
  ancestors.
• This is the lineage of photosynthetic bacteria
  that generate oxygen.
• Some chloroplasts appear to reflect secondary
  endosymbiosis - a eukaryote has engulfed and
  enslaved another eukaryote.
• These secondary plastids have more than two
  membranes.
• However, there are two unrelated types of algae
  in which a highly reduced nucleus (called the
  NUCLEOMORPH) remains associated with the
  secondary plastid.

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Secondary Endosymbiosis

• This figure shows the process of secondary
  endosymbiosis.
• Notice the primary endosymbiosis that occurred
  first.
• Plants, Red algae
• Then a second eukaryote became the host for the
  first eukaryote.
• In cryptomonads and chlorarachniophytes the
  nucleomorph was retained - it was lost in other
  lineages.

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Organelles Typically Show Maternal Inheritance

• Different mitochondrial genotypes are inherited
  from the maternal ancestor alone in vertebrates.

• Chloroplasts also exhibit this pattern of
  inheritance.
• mtDNA from the male parent are occasionally found
  in zygotes.
• Some organisms show a higher rate of paternal
  transmission.
• If an individual multiple HAPLOTYPES of mtDNA or
  cpDNA, the individual is said to be
  HETEROPLASMIC.

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Mitochondrial DNA Mutations

• Human mitochondrial mutations resulting in
  disease phenotypes have been found
• All diseases resulting from changes in
  mitochondrial DNA are fundamentally the result of
  malfunctions of the respiratory chain for
  oxidative phosphorylation.
• The phenotypic effects of mitochondrial mutations
  reflect the extent to which a tissue relies on
  oxidative phosphorylation the central nervous
  system is most sensitive, followed by skeletal
  muscle, heart muscle, kidney, and liver.
• Some mitochondrial diseases are
• Leber's hereditary optic neuropathy (LHON) - loss
  of vision and cardiac dysrhythmia.
• Myoclonic epilepsy and ragged red fiber disease
  (MERRF) - central nervous system abnormalities
  and deficiencies of skeletal and cardiac muscle
  function.
• Kearns-Sayre syndrome - neuromuscular symptoms
  including paralysis of eye muscles, dementia, and
  seizures.
• A list of mitochondrial diseases is available at
  http//www.gen.emory.edu/MITOMAP/disease.html

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Mitochondrial DNA Mutations

• Human mitochondrial mutations resulting in
  disease phenotypes have been found
• Mutant mtDNA genomes are maintained in a
  heteroplasmic state and will only cause the
  disease phenotype if they exceed a certain
  percentage of the total mtDNA genomes present.
• This leads to inheritance that appears sporadic.

• Red individuals show the phenotype due to random
  changes in the percentage of mutant haplotypes
  present.
• The numbers show the percentage of mutant
  haplotypes.

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Mitochondrial and Nuclear Genes

• Nuclear genes can alter mitochondrial phenotypes.
• Some nuclear genes are necessary for mt function.
• Remember, many organelle complexes (e.g., the
  electron transport chain and photosynthetic
  reaction centers) are nuclear encoded.
• In organisms that are not absolutely dependent
  upon mt function (which include some yeasts)
  mtDNA mutations and mutations in nuclear gene
  necessary for mt function produce similar
  phenotypes.
• Usually called PETITE mutants because they show a
  slow growth phenotype.
• Nuclear genes can also act as suppressors of
  mtDNA mutations.
• The text describes cytoplasmic male sterility
  (CMS) in maize.
• CMS maize fails to produce pollen in the male
  flowers.
• But nuclear encoded Rf genes can act as
  suppressors.

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Infectious Inheritance

• Bacteria or viruses that replicate within cells
  can also show distinct patterns of inheritance.
• In some cases, any mixing of the cytoplasm can
  transmit the infectious particles. The text
  presents the example of kappa particles in
  Paramecium.
• An additional level of complexity is found in the
  kappa particle example since there is also a
  Mendelian gene that controls whether or not the
  bacteria can grow.
• In other cases, the inheritance may be maternal
  because the bacteria infect through the egg.
• Wolbachia is a bacterium that infects many
  insects and shows this pattern of inheritance.
• Wolbachia strains can distort the sex ratio to
  increase the chance of transmission.

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How can patterns ofinheritance be distinguished?

• One question you may have is how to distinguish
  between sex-linkage, organellar inheritance, and
  maternal effects.
• Superficially, all of these patterns of
  inheritance seem similar.
• However, it is important to remember that the
  differences
• Sex-linked inheritance is based upon the fact
  that organisms with sex chromosomes will be
  hemizygous for genes on the chromosome present in
  both sexes.
• So the chance that the heterogametic sex will
  show recessive phenotypes is higher than the
  chance that the homogametic sex will. But both
  sexes can show the phenotype.
• If the heterogametic sex has the recessive allele
  and the homogametic sex does not carry the
  recessive allele, all F1 progeny will show the
  dominant phenotype.
• If the homogametic sex has the recessive
  phenotype all F1 progeny of the heterogametic sex
  will show the recessive phenotype.

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How can patterns ofinheritance be distinguished?

• Both organellar inheritance and some infectious
  inheritance is based upon the transmission of the
  organelles or agents through the female gamete.
• So all organisms will show the phenotype of their
  mother - and daughters will transmit this trait
  to all of their progeny.
• Heteroplasmy can complicate this - but even in
  this case the phenotype can be thought of as an
  extension of the presence of mutant DNA.
• So, males will never transmit the observable
  phenotype, but will always transmit the mutant
  DNA but only some individuals that have the
  mutant DNA will show the phenotype.
• Thus, it is probably best thought of as a mutant
  phenotype with limited penetrance.
• Maternal effects are based upon the packaging of
  gene products into female gametes.
• Thus, they only impact a single generation. The
  offspring of an individuals progeny will reflect
  only the genotype of the that offsprings
  immediate maternal ancestor.

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Additional Forms of Infectious Inheritance

• Plants can be infected with agents called
  VIROIDS.
• Viroids consist only of RNA and do not have any
  protein coding regions - in sharp contrast to
  viruses.
• Prions are infectious protein particles.
• The best know prion is the causative agent of
  mad cow disease (Bovine Spongiform
  Encephalopathy).
• Excellent information on mad cow disease is
  available from http//www.mad-cow.org.
• Prions can exist in multiple forms. These forms
  have different biological activities.
• Specific forms are associated with pathology,
  such as the spongiform encephalopathy.

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Additional Forms of Infectious Inheritance

• Plants can be infected with agents called
  VIROIDS.
• Viroids consist only of RNA and do not have any
  protein coding regions - in sharp contrast to
  viruses.
• Prions are infectious protein particles.
• Specific forms of prion proteins in can act in
  some way to convert prions in the other form to
  the prion form - but this conversion is often
  largely unidirectional.
• This makes prions are infectious.
• Prions are not unique to vertebrates - yeast is
  known to have two prions that show infectious
  inheritance.
• One is the PSI factor - PSI yeast can suppress
  some mutations that cause early termination of
  proteins.
• PSI is a protein that regulates the termination
  of protein synthesis
• The prion form of PSI is not functional - so PSI
  yeast will read through stop codons (sometimes).