Organelles and Subcellular Genetics

Organelles are internal cellular structures that perform dedicated functions.

Oraganelles includes tructures such as ribosomes, mitochondria, chloroplasts (the site of photosynthesis in plants and other photosynthesizing organisms), endoplasmic reticulum (ER), Golgi apparatus, and lysosomes.

The mitochondrion of all eukaryotes and the chloroplasts of plant cells are the only organelles that have their distinct genomes. These genomes are made of a single, circular DNA molecule denoted mtDNA in mitochondrion and ctDNA in chloroplast. The replication and the mode of inheritance of organelle genomes are distinct from the nuclear genomes.

Mitochondrial genomes vary in size, among species, by up to one order of magnitude. Animal cells have a genome of approximately 16 kb (kilobases, 1,000 bases) and represent the smallest mitochondrial genomes in eukaryotes. Yeast possess a much larger genome that varies among the different strains but is about 80 kb, with the whole yeast mitochondrial DNA making up 18% of the total DNA of the yeast. Plant mitochondrial genomes are the largest and most complex. They show an extremely wide range of variation in DNA size. The smallest plant mitochondrial genome is around 100 kb, which make it very difficult to isolate in intact form. These genomes contain short homologous sequences that may undergo recombination thus generating small circular molecules that coexist with the intact ctDNA.

Eukaryotic cells may contain up to several hundred mitochondria. These mitochondria contain their own replication, transcription and translation systems. Nuclear genes, however, encode the majority of mitochondrial proteins which are synthesized in the cytosol and then targeted to the mitochondrion. Each mitochondrion can contain up to ten copies of the circular genome. A special DNA polymerase replicates the mitochondrial genome. The complete sequencing and mapping of several mammalian mitochondrial genomes show extensive similarity in organization. The mammalian mitochondrial genome is extremely compact with many overlapping genes and no introns. This genome codes for 13 essential genes of biochemical pathways (e.g., oxidative phosphorylation), two rRNAs, and 22 tRNAs. The genetic code of mitochondria differs from the standard genetic code used by the cytosolic ribosomes and the bacterial ribosomes. There at least two codons for all the aminoacids and plus four termination codons. The yeast mitochondrial genome is much larger, but codes for only eight proteins. The mitochondrial products synthesized by this genome, both RNAs and proteins, are similar to those produced by the mammalian mitochondria. The most distinguishing feature of the yeast genome is the existence of interrupted loci. The introns in some are so large that their size is almost as large as the whole mammalian mitochondrial DNA.

The genomes of the chloroplast of different plant cells are relatively large but show considerable difference in overall length, between 100 kb and 200 kb. The complete sequence and mapping has been determined for some organisms. These sequences show a highly conserved overall gene number and organization in the different species. These genomes usually encode for 50–100 proteins as well as rRNAs and t RNAs. The majority of the characterized proteins are involved in gene expression, electron transfer or in photosynthesis. The latter form complexes located in the thylakoid membranes. Both protein-coding genes and those coding for tRNAs contain introns.

Both mitochondrial and chloroplast genomes are believed to have evolved through endosymbiosis. This model of organelle evolution proposes that eukaryotic cells captured bacteria that later provided the function of mitochondria and chloroplast. Phylogenetic studies based on DNA sequence analysis suggest that mitochondria and chloroplasts evolved separately from eubacterial lineages related to purple bacteria and cyanobacteria, respectively. Mitochondrion is presumed to have evolved from a species that is very similar to Rickettsia, an obligate the intracellular bacteria. Both mitochondria and chloroplasts follow a non-Mendelian mode of inheritance usually referred to as extranuclear or cytoplasmic inheritance. Most mtDNA is inherited from egg cells and thus show a maternal pattern of inheritance. This has implications both in studies of evolution between different populations of species as well as in the inheritance of some genetic diseases.

Because of the relative simplicity of the mitochondrial genome, genetic manipulation has advanced considerably. The first humans with half the nuclear genome from one mother and the mitochondrial genome from a donor mother have been delivered and are reported healthy. This genetic manipulation has now been carried out on about thirty children in the United States. Technically, this amounts to a kind of germline genetic modification and has, therefore, caused great reservation among the international biomedical community. Many scientists and physicians argue that there are serious ethical issues that should be addressed before such a practice should be allowed.