Cytoplasmic Inheritance

Most of the genetic information of a eukaryotic cell resides in its nucleus, and some is found in the cytoplasm. Each mitochondrion and chloroplast contains several copies of specific DNA molecules that carry some of the genetic information for the organelle; the rest is encoded in nuclear genes. Organelle genes are transcribed and translated in the organelles themselves through a genetic code that diverges in many cases from the standard one, while the proteins encoded in nuclear genes are imported into the organelle after their protein biosynthesis on cytoplasmic ribosomes. As a consequence of this shared genetic determination, there are many cases of nuclear and organelle mutants that exhibit similar phenotypes.

Most organelle genomes consist of circular double-stranded DNA molecules (Table 1). After considerable controversy, it seems clear that many mitochondrial DNA molecules are linear rather than circular. 

Table 1. Some Genomes from Mitochondria and Chloroplasts, with Indication of Their Size, Number of Confirmed or Putative Translatable Genes (Open Reading Frames, ORFs), and number of genes for transfer RNA and ribosomal RNA^a

^a Data taken from the indicated EMBL sequence accession numbers.

Organelles may contain molecules of DNA other than their own chromosomes. Examples are the two linear plasmids of the mitochondria of Zea mays that result in the absence of functional pollen )androsterility); they are very useful for the commercial production of hybrid seed.  Another example is kalilo, a linear plasmid of Neurospora crassa that blocks mitochondrial functions when it integrates into the mitochondrial DNA; the result is senescence, the inability for indefinite vegetative growth.

 Other cytoplasmic bodies with their own genetic information range from various self-replicating particles to viruses and complete endosymbiotic cells. Their genomes may consist of DNA or RNA. First to be discovered were the kappa particles of Paramecium aurelia (1), but many others are known, such as the killer particles in Saccharomyces cerevisiae and the s particles that render Drosophila melanogaster specially sensitive to carbon dioxide.

1. Heteroplasmons and Mosaicism

 A cell contains numerous copies of organelle DNA molecules, up to several thousand, and these need not be identical (heteroplasmon). Organelle genomes are notoriously unstable and suffer frequent point mutations and large rearrangements. Heteroplasmons can be produced by these spontaneous changes or by cell fusion. Contrary to the usual behavior of heterozygotes, the relative proportion of two variants in a heteroplasmon is not fixed, giving rise to mosaicism in cell clones.

 In some cases, one of the variants imposes itself because of its faster reproduction. Thus, most petite mutants of the yeast Saccharomyces cerevisiae, lacking aerobic metabolism, carry changes in their mitochondrial DNA. Some of these are called suppressive, because mutant mitochondria displace wild-type mitochondria in heteroplasmons. Wild-type mitochondria, on the other hand, impose their phenotype when mixed with mitochondria that carry petite mutations called neutral.

In other cases, the two variants may be found in various relative proportions, or even pure, in different cells, as would be expected from random genetic drift. Many variegated ornamental plants exhibit patches or streaks of different colors in their stalks and leaves, ranging from normal green to whitish. This phenotype may have many causes; in the plant Mirabilis jalapa, the colors depend on the presence of mutant chloroplasts, mixed with the normal ones in various proportions.

 Recombination can occur between the various forms of chloroplast DNA or mitochondrial DNA in heteroplasmons, as shown for example for chloroplast markers of Chlamydomonas reinhardtii and mitochondrial markers in Saccharomyces cerevisiae.

 2. Heterokaryon Test

 The fusion of two cells that differ in both nuclear and cytoplasmic markers results in cells that are at the same time heterokaryons and heteroplasmons. Vegetative multiplication of the heterokaryon produces three kinds of cells: heterokaryons and two homokaryons, one for each of the kinds of nuclei. Cytoplasmic traits may segregate in various ways, all independent of the segregation of the nuclei. Homokaryotic segregants may show new combinations of cytoplasmic and nuclear markers. This test requires that the nuclei in the heterokaryon do not fuse, but remain separate, so that they can segregate to different daughter cells. The test has been extended to the yeast Saccharomyces by the use of dominant kar mutations that block nuclear fusion after mating, thus giving rise to heterokaryons.

 3. Reciprocal Crosses

The results of reciprocal crosses offer a test for cytoplasmic inheritance when the two parents do not contribute equally to the cytoplasm of the zygote. The most frequent case in animals and plants is matrilinear inheritance, in which all individuals inherit from their mothers only, because of the larger size and contribution of female gametes. Examples are the variegation in Mirabilis, the first report of this heredity pattern (2), androsterility in Zea, and several human diseases due to mitochondrial mutations, such as Leber's hereditary optic neuropathy.

The matrilinear rule is not absolute. The s particles of Drosophila are transmitted most often by the ova (egg), but sometimes by sperm. Chloroplasts may be provided by the male, as in the conifers, or by both parents, as in Oenothera. Mammals have powerful mechanisms to exclude the mitochondrial DNA of the sperm from the embryo, and the failure of these mechanisms might produce exceptions to the matrilinear rule.

 Uniparental inheritance is observed with the poky mitochondrial mutants and the kalilo plasmid in the fungus Neurospora crassa. When two haploid strains of different mating type, A or a, arecrossed, either can provide the large protoperithecia or the small conidia that fuse to produce the zygote. All offspring inherit the cytoplasmic markers from the protoperithecia donor, irrespective of its mating type.

 Uniparental inheritance can occur even when the gametes are similar in size, as in Chlamydomonas reinhardtii. The zygote is formed by the fusion of seeming identical cells of the two mating types, called mt⁺ and mt^–. Almost all the offspring inherit the chloroplast markers of the mt⁺ parent only, because the DNA of the mt^– parent is usually destroyed (3). There are cases of maternal inheritance that are not due to cytoplasmic genes.

References

1. T. M. Sonneborn (1938) Science 88, 503. 

2. C. Correns (1909) Z. Indukt. Abst. Vererbungsl. 1, 291–329. 

3. R. Sanger (1954) Proc. Natl. Acad. Sci. USA 40, 356–363.