Nucleotide sequence evidence for rapid genotypic shifts in the bovine mitochondrial DNA D-loop

Abstract

Mitochondrial DNA (mtDNA) is unusual in its rapid rate of evolution and high level of intraspecies sequence variation. The latter is thought to be related to the strict maternal inheritance of mtDNA, which effectively isolates within a species mitochondrial gene pools that accumulate mutations and vary independently. A fundamental and as yet unexplained aspect of this process is how, in the face of somatic and germ-line mtDNA ploidy of 10(3) to 10(5) (refs 4, 5), individual variant mtDNA molecules resulting from mutational events can come to dominate the large intracellular mtDNA population so rapidly. To help answer this question, we have determined here the nucleotide sequence of all or part of the D-loop region in 14 maternally related Holstein cows. Four different D-loop sequences can be distinguished in the mtDNA of these animals. One explanation is that multiple mitochondrial genotypes existed in the maternal germ line and that expansion or segregation of one of these genotypes during oogenesis or early development led to the rapid genotypic shifts observed.

Complementation of mutant and wild-type human mitochondrial DNAs coexisting since the mutation event and lack of complementation of DNAs introduced separately into a cell within distinct organelles.

“…Although the present work has not addressed directly the question of whether fusion occurred between organelles carrying different mtDNAs, the most plausible hypothesis is that the lack of interaction between the two genomes reflected their physical segregation in separate organelles, i.e., absence of mitochondrial fusion. There is other evidence in the literature that supports the idea that two types of mtDNA originally located in separate organelles tend to remain segregated in mammalian cells, including the gradual elimination of HeLa cell mtDNA in hybrids of HeLa cells and fibroblasts (21,49) and the complete switch, in only one or a few generations, of mtDNA genotypes in Holstein cows (2,28,36). A model assuming that the unit of segregation of mammalian mtDNA is the organelle itself and that the rapidity of segregation of mitochondrial alleles within heteroplasmic oocytes is therefore influenced by whether the individual organelles themselves are homoplasmic or heteroplasmic (23) likewise argues in favor of the genetic independence of the individual mitochondria within a mammalian cell.…”

Unsolved issues related to human mitochondrial diseases

“…Segregation also occurs before birth and has been involved in the rapid return to homoplasmy of heteroplasmic mtDNA molecules through what was called the genetic bottleneck [38]. It can theoretically take place at any step from the differentiation of primordial germinal cells, through their maturation into mature ovule, fecundation and embryogenesis.…”

Mitochondrial molecular clocks and the origin of the major Otocephalan clades (Pisces: Teleostei): A new insight

“…Considering the effect of rate variation among a small number of genes, it is not surprising that the analyses based on partial mitochondrial gene sequences may sometimes be biased. As a genetic marker, animal mitochondrial DNA (mtDNA) has distinct characteristics, such as relatively fast evolutionary rate, lack of recombination, and maternal inheritance (e.g., Brown et al, 1979;Olivio et al, 1983). One way of reducing the problems associated with molecular clock dating is to compare long DNA sequence data (e.g., Inoue et al, 2001aInoue et al, , 2003Yang and Yoder, 2003).…”