Harpers

DNA ORGANIZATION, REPLICATION, & REPAIR / 323Table 36–3. Some major features of the structureand function of human mitochondrial DNA. 1• Is circular, double-stranded, and composed of heavy (H)and a light (L) chains or strands.• Contains 16,569 bp.• Encodes 13 protein subunits of the respiratory chain (of atotal of about 67):Seven subunits of NADH dehydrogenase (complex I)Cytochrome b of complex IIIThree subunits of cytochrome oxidase (complex IV)Two subunits of ATP synthase• Encodes large (16s) and small (12s) mt ribosomal RNAs.• Encodes 22 mt tRNA molecules.• Genetic code differs slightly from the standard code:UGA (standard stop codon) is read as Trp.AGA and AGG (standard codons for Arg) are read as stopcodons.• Contains very few untranslated sequences.• High mutation rate (five to ten times that of nuclear DNA).• Comparisons of mtDNA sequences provide evidence aboutevolutionary origins of primates and other species.1 Adapted from Harding AE: Neurological disease and mitochondrialgenes. Trends Neurol Sci 1991;14:132.crossing over occurs as shown in Figure 36–9. Thisusually results in an equal and reciprocal exchange ofgenetic information between homologous chromosomes.If the homologous chromosomes possess differentalleles of the same genes, the crossover may producenoticeable and heritable genetic linkage differences. Inthe rare case where the alignment of homologous chromosomesis not exact, the crossing over or recombinationevent may result in an unequal exchange of information.One chromosome may receive less geneticmaterial and thus a deletion, while the other partner ofthe chromosome pair receives more genetic materialand thus an insertion or duplication (Figure 36–9).Unequal crossing over does occur in humans, as evidencedby the existence of hemoglobins designatedLepore and anti-Lepore (Figure 36–10). The fartherapart two sequences are on an individual chromosome,the greater the likelihood of a crossover recombinationThus, in diseases resulting from mutations of mtDNA,an affected mother would in theory pass the disease toall of her children but only her daughters would transmitthe trait. However, in some cases, deletions inmtDNA occur during oogenesis and thus are not inheritedfrom the mother. A number of diseases have nowbeen shown to be due to mutations of mtDNA. Theseinclude a variety of myopathies, neurologic disorders,and some cases of diabetes mellitus.GENETIC MATERIAL CAN BE ALTERED& REARRANGEDAn alteration in the sequence of purine and pyrimidinebases in a gene due to a change—a removal or an insertion—ofone or more bases may result in an alteredgene product. Such alteration in the genetic material resultsin a mutation whose consequences are discussedin detail in Chapter 38.Chromosomal Recombination Is One Wayof Rearranging Genetic MaterialGenetic information can be exchanged between similaror homologous chromosomes. The exchange or recombinationevent occurs primarily during meiosis inmammalian cells and requires alignment of homologousmetaphase chromosomes, an alignment that almostalways occurs with great exactness. A process ofFigure 36–9. The process of crossing-over betweenhomologous metaphase chromosomes to generate recombinantchromosomes. See also Figure 36–12.