Speaker: Passorn Wonnapinij
Title: A Reduction of Mitochondrial DNA Molecules During Embryogenesis Explains the Rapid Segregation of Genotypes
Date: Fri, 9/26/2008
Time: 6.00 pm
Location: GLC room C
Abstract:
Mammalian mitochondrial DNA (mtDNA) is inherited principally down the maternal line, but the mechanisms involved are not fully understood. Females harboring a mixture of mutant and wild-type mtDNA (heteroplasmy) transmit a varying proportion of mutant mtDNA to their offspring. In humans with mtDNA disorders, the proportion of mutated mtDNA inherited from the mother correlates with disease severity. Rapid changes in allele frequency can occur in a single generation. This could be due to a marked reduction in the number of mtDNA molecules being transmitted from mother to offspring (the mitochondrial genetic bottleneck), to

the partitioning of mtDNA into homoplasmic segregating units, or to the selection of a group of mtDNA molecules to repopulate the next generation. Here we show that the partitioning of mtDNA molecules into different cells before and after implantation, followed by the segregation of replicating mtDNA between proliferating primordial germ cells, is responsible for the different levels of heteroplasmy seen in the offspring of heteroplasmic female mice.

Selected references:

Cree. L.M., et al., A reduction of mitochondrial DNA molecules during embryogenesis explains the rapid segregation of genotypes. Nature Genetics, 2008. 40, p. 249-254.

Chinnery, P.F., et al., The inheritance of mitochondrial DNA heteroplasmy: random drift, selection or both? Trends in Genetics, 2000. 16(11): p. 500-505.

Khrapko, K., Two ways to make an mtDNA bottleneck. Nature Genetics, 2008. 40: p. 134-135.