Genetics - Chapter 7

• • Some observations indicate an apparent extra-nuclear influence on the phenotype

  • With the discovery of DNA in mitochondria and chloroplasts, extra-nuclear inheritance is now recognized as an important aspect of genetics
• • One variety of extranuclear inheritance is organelle heredity, in which DNA contained in mitochondria or chloroplasts determines certain phenotypic characteristics of the offspring

  • A second type involves infectious heredity, resulting from the symbiotic or parasitic association with a microorganism
• • The third variety involves the maternal effect on the phenotype, in which nuclear gene products are stored in the egg and then transmitted through the ooplasm to the offspring

  • The gene products in the ovule are distributed to the cells of the developing embryo and influence its phenotype
• Inheritance of chloroplast or mitochondrial traits is often determined by the phenotype of the ovule source
• Analysis of inheritance patterns resulting from mutant alleles in chloroplast and mitochondria has been difficult:

  – The function of these organelles is dependent on gene products from the nucleus and the organelle DNA, making the origin of mutations affecting organelle function difficult

  – Organelles are contributed to each progeny cell and exhibit great variation (heteroplasmy), making detection of the mutation hence analysis more complicated than Mendelian inheritance
• Mitochondrial studies (Mitchell & Mitchell, 1952) reveal that mitochondria likewise contain a diverse genetic system, and mutations are transmitted through the cytoplasm
• The endosymbiotic theory (Lynn Margulis et al.) states that mitochondria and chloroplasts arose independently about 2 billion years ago from free-living bacteria

  These progenitors possessed the abilities now attributed to these organelles—aerobic respiration and photosynthesis, respectively
• One variety of extranuclear inheritance is organelle heredity, in which DNA contained in mitochondria or chloroplasts determines certain phenotypic characteristics of the offspring
• A 2nd type involves infectious heredity, resulting from the symbiotic or parasitic association with a microorganism
• The 3rd type involves the maternal effect on the phenotype, in which nuclear gene products are stored in the egg and then transmitted through the ooplasm to the offspring
• The gene products in the ovule are distributed to the cells of the developing embryo and influence its phenotype
• Analysis of inheritance patterns resulting from mutant alleles in chloroplasts and mitochondria has been difficult because

  1. The function of these organelles is dependent on gene products form the nucleus and the organelle DNA, making the origin of mutations affection organelle function difficult
  2. Organelles are contributed to each progeny cell and exhibit great variation (heteroplasmy), making detection of the mutation hence analysis more complicated than Mendelina inheritance
• Mitochondrial studies (Mitchell and Mitchell, 1952) reveal that mitochondria likewise contain a diverse genetic system, and mutations are transmitted through the cytoplasm
• Knowledge of mitochondrial and chloroplast DNA helps explain organelle heredity
• The endosymbiotic theory (Lynn Margulis) states that mitochondria and chloroplasts arose independently about 2 billions years ago from free-living bacteria. These progenitors possessed the abilities now attributed to the organelles - aerobic respiration and photosynthesis
• The endosymbiotic theory proposes that these bacteria were engulfed by larger eukaryotic cells, and a beneficial symbiotic relationship developed
• (endosymbiotic theory) evolution of the host cell showed alterations, primary of which was the transfer of many genes from the invading bacterium to the nucleus of the host
• The amount of DNA remaining in today’s mitochondrial genome is miniscule (<10%) compared to the DNA of the free-living bacteria from which it was derived
• Chloroplast DNA ranges from 100-223 kb in lengths, and the genes carried on the DNA encode products involved in photosynthesis and translation. Mutations in these genes may inactivate photosynthesis
• Mitochondrial DNA (mtDNA) is smaller than the DNA in chloroplasts, introns are absent, and gene repetitions are rare. Most of the protein encoding genes are located on a single strand.
• Replication in mitochondria is dependent on genes encoded by nuclear DNA
• Mutations in mtDNA cause human disorders
• Human mtDNA contains 16,569 base pairs coding for 13 of over 70 proteins required to aerobic cellular respiration, and is very susceptible to mutations
• mtDNA is very susceptible to mutations

  • Doesn’t have histones to protect from mutations
  • Mitochondria have high concentrations of reactive oxygen species (ROS) generated by cell respiration (ROS damages organelle contents, proteins, lipids, mtDNA)
• A zygote receives a large number of organelles through the egg; a mutation in one or a few will be diluted out by many mitochondria that lack the mutation and function normally
• Heteroplasmy - the condition in which adult cells have a variable mixtures of normal and abnormal organelles
• For a human disordered to be attributed to mtDNA

  1. The inheritance must exhibit a maternal inheritance pattern
  2. The disorder must reflect a deficiency in the bioenergetic function of the organelles
  3. There must be a specific mutation in a mitochondrial gene
• 3 disorders arising from mtDNA are

  • Myoclonic epilepsy and ragged red fiber disease (MERRF)
  • Leber’s hereditary optic neuropathy (LHON)
  • Kearns-Sayre syndrome (KSS)
• MERRF

  • Consistent with maternal inheritance
  • Only offspring of affected mothers inherit the disorder
  • Affected fathers offspring - normal
• MERRF characteristics

  • Ataxia - lack of muscular coordination
  • Deafness
  • Dementia and epileptic seizures
  • Ragged red skeleton muscles fibers exhibit blotchy red patches
  • Neurological disorders due to the lack of energy supply
  • Proliferation of aberrant mitochondria
• LHON

  • Maternal inheritance
  • Sudden bilateral blindness
  • Average age of vision loss is 27
  • Mutation of the gene coding for NADH dehydrogenase
• KSS

  • Loss of vision and hearing
  • Heart conditions
  • Deletions of certain areas of DNA causes this disorder
• The study of hereditary mitochondrial-based disorders provides insights into the

  • Critical important of this organelle during normal development
  • Relationship between mitochondrial functions and neuromuscular and neurological disorders
• Defective mtDNA is implicated in the aging process
• In maternal effect, the maternal genotype has a strong influence during early development
• Maternal effects implies that an offspring’s phenotype is under control of nuclear gene products present in the egg
• The nuclear genes of the female gamete are transcribed, and the genetic products accumulate in the egg cytoplasm
• These products are distributed among the newly formed cells, influencing patterns/trials establish early in development
• For maternal effect genes, the genotype of the female parent and not that of the embryo determines the phenotype of the offspring
• Embryonic development in drosophila is strongly controlled by maternal effect genes. The protein products of these genes function to activate other genes