Cytoplasmic Inheritance:

Mitochondria and chloroplasts are semiautonomous organelles in eukaryotic organisms that contain DNA. Both mtDNA and cpDNA encode some but not all of the information needed for function and replication.Both have circular DNAs that include genes for ribosomes, t-RNAs and mRNAs for some of the proteins that function inside the organelle. Most of the proteins are subunits of complexes used in photosynthesis or oxidative phosphorylation. Only m-RNA from the organelle is translated inside the organelle; other proteins enter via signal peptides. The DNA and RNA polymerases for transcription and translation of mt-DNA are coded by nuclear genes. Mammalian mtDNA is a circle of ≅16,569 bp. It replicates via a D-loop mechanism from one origin. The origin region also has promoters for translation in both directions. The long transcripts are cleaved by excision of t-RNAs that also serve as spacers.

In most organisms, the organelles pass through the egg and not the sperm, giving a strict maternal pattern of inheritance for any mutations that may be present in the organelle DNA.

The organelles are found in multiple copies that may also contain multiple copies of the DNA. They appear to segregate randomly to daughter cells in mitosis and meiosis.

Mutations in the organelle DNA create a "heteroplasmic", ie cells with two or more genetically different types of organelles. In general, chance segregation may result in daughter cells with more or less copies of the defective organelle. Since the organelles are essential for energy metabolism, and the encoded proteins must interact in complexes there is

often strong selection in favor of normal copies. Viable defects tend to be relatively minor changes in function, but can have serious consequences.

In plants, the assortment of functional versus nonfunctional chloroplasts (caused by defects in the ctDNA) can give variegated plants, where some leaves or branches are white, others green and others show continued sectoring. If flowers from a white sector are fertilized with any pollen, all the progeny will be white. Flowers from green sectors give all green

progeny, even if the pollen came from a white sector. Pollen from a white sector will not transmit the trait, no matter what the cytotype of the female.

Examples of cytoplasmic inheritance in human include LHON (Lebers Hereditary Optic Neuropathy).

The condition involves a gradual to rapid loss of central vision, often starting around age 30 but patients from 1 to 70 have been reported.

LHON is much more common in males than females. The condition has been traced to defects in ATP synthesis Complex I in mitochondria. At least 17 different missense mutations have been described altering various mtDNA-encoded Complex I components, the most common being "11778G-A" a mutation that changes arginine to histidine at position 340

in subunit ND4. Severity differs among alleles. Mothers with less than 80% variant mtDNA have relatively few affected progeny compared to those with 100%. As expected for a mitochondrial trait, affected males do not pass LHON to their progeny. Another example of human "cytoplasmic inheritance" is MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) which most often is caused by an A to G transition in a mitochondrial leu-tRNA. (Other mutations have been identified). Others are KSS (Kearns-Sayre syndrome) which leads to loss of vision, hearing and heart problems when large fractions of defective mitochondria accumulate in the relevant cells,

MMC (maternally inherited myopathy and cardiomyopathy where energy demanding muscle cells are greatly affected.

'Cytoplasmic male sterility' (CMS)in plants is a good example of a practical application of a mtDNA alteration. Plants with "sterile" cytoplasm (often reflecting energy deficiency in tapetal cells where meiosis is occurring) do not make functional pollen unless the plant also has a dominant restorer nuclear gene. For example, a plant that is [s]-rr is sterile (the square brackets indicate the cytotype) while [s]-Rror [s]-RR plants are fertile. Any [F] plant is fertile, even if it is rr. For a time in the 1960s, essentially all the maize hybrids sold to farmers in the US were made using 'T' (Texas for Texas A&M where it was discovered) male sterile cytoplasm which can be restored to fertility by nuclear gene Rf-2.

Unfortunately, the same mutation causes the plants to be susceptible to the fungus that causes Southern corn leaf blight. A 1970 epidemic started early in Florida and moved through the midwest corn belt as the corn crop matured. The episode pointed out quite well the inherent risk of "monoculture" and led to the identification of a number of different sources of male sterility as well as a return to the old fashioned way of making crosses by detasseling female plants before they could self pollinate. However, for many crop and vegetable species, hand-made crosses are extremely difficult to make so CMS is a very valuable alternative. For example, all of hybrid sorghum production is based on use of various CMS and restorer gene combinations.

Petite yeast. Even organisms where mating is by fusion can show cytoplasmic inheritance. Yeast (Saccharomyces cerevisae) can either grow using O2 or can grow anaerobically by fermentation. Anaerobic growth results in small (petite) colonies. Nuclear mutations that prevent oxidative phosphorylation such as cytochrome C defective haploids are petite even in O2. If crossed to a normal strain, (petite X grande) the diploid formed produces progeny (the products of meiosis) in a typical 1:1 nuclear gene manner. However when some haploid petite strains are fused to normal grande haploids of the opposite mating type the diploids are grande as before,but when meiosis occurs all the progeny are grande also. In this case, the petites have no or defective, nonfunctional mt-DNA, so the trait is not recovered in any daughter cells. However some petites, called suppressive petites, have abnormal AT-rich mt-DNA that out- replicates normal mitochondria. Crosses of these strains to grandes lead to high frequency of petite progeny and progeny that produce sectors of petite cells.

Fungi in general have a much larger mitochondrial genome than higher eukaryotes. They also have many unusual mt-DNA features such as self- splicing introns and large AT rich regions and may harbor plasmids. The ability to identify different yeast antibiotic resistance mutants that were traced to mitochondrial defects was useful in showing that rare mt-DNA recombinations can occur.

Higher plants seem to use splicing and editing fairly frequently to alter mt-RNA transcripts before translation.

Exceptions to the strict maternal inheritance of organelle DNA are known. An example is Loblolly pine, a Gymnosperm where mitochondria are transmitted paternally but chloroplasts show maternal inheritance. Many gymnosperms seem to favor male transmission of both organelles.

Apparent cases of maternal inheritance sometimes can be misleading. In maternal effect,a protein or imprint provided in the egg by the mother can permanently affect phenotype. The best known example is the direction of shell coiling in snails. Dextral or "right" coiling is actually dominant and any female that is DDor Ddwill have all right coiling progeny. A ddfemale mated to a DDmale will give all Ddprogeny, but they are left coiling since they did not receive the D product in the egg. If these Ddleft coiling snails are inter-mated, all the progeny will be right coiling, even the dds. However in the next generation (selfing is possible) the 3:1 ratio expected in the F2will show up.

Infectious heredity refers to cases where the phenotype is the result of a bacterial or virus infection that can pass through the egg but not through sperm. Classic examples include CO2 sensitivity in Drosophila and the "killer" trait in Paramecium.