Tracking mtDNA Heteroplasmy through Multiple Generations in the North Atlantic Right Whale (Eubalaena glacialis)

Abstract

Mitochondrial heteroplasmy has been identified in a variety of species and can result from either paternal leakage, whereby sperm mitochondria enter the ova during fertilization, or more commonly by the "survival" and proliferation of mutant variants within an organism. From an evolutionary perspective, this process represents the generation of new mitochondrial diversity within a species. Although this has been documented in some mammalian species, it has been reported from relatively few wild mammalian populations and in no wild nonhuman population has the transfer and segregation of mitochondrial heteroplasmy been tracked through multiple generations. We report on the first case of the identification and tracking of mitochondrial control region heteroplasmy through 3 generations in the North Atlantic right whale, Eubalaena glacialis. We also identify the full segregation to the mutant variant within a single generation and thus the development of a new haplotype (haplotype G) in a maternal lineage of this endangered species. Witnessed here is the generation of mitochondrial diversity in a genetically depauperate species.

Gender-Associated Mitochondrial DNA Heteroplasmy in Somatic Tissues of the Endangered Freshwater MusselUnio crassus(Bivalvia: Unionidae): Implications for Sex Identification and Phylogeographical Studies

“…However, mutations in some copies of mitochondrial genomes are in trend to be lost by genetic drift in a few generations due to bottlenecks of mtDNA during oogenesis or negative selection on cells carrying a high level of mtDNA mutations (e.g., Chinnery et al., ; Cree et al., ; Khrapko, ). Although heteroplasmy is thought to be detrimental (Breton et al., ), in some taxa the polymorphism in mitochondrial sequences have become fixed (e.g., Doublet et al., ; McLeod and White, ). The unique example of stable and gender‐associated heteroplasmy resulting from an unusual type of mtDNA inheritance is observed among some taxa within Bivalvia.…”

A novel and effective separation method for single mitochondria analysis

“…A lot of research has been done to analyse mitochondrial heteroplasmy on different species, tissues and levels (e.g. Ashley et al, 1989;Cavelier et al, 2000;Deckman et al, 2008;He et al, 2010;Jacobs et al, 2007;Lehtinen et al, 2000;Lutz-Bonengel et al, 2008;McLeod and White, 2010;Woloszynska, 2010). We have chosen single mitochondria, which are approx.…”

Segregation of point mutation heteroplasmy in the control region of dog mtDNA studied systematically in deep generation pedigrees

“…For example, [43] found that five out 135 human mother–child comparisons had a strong shift in heteroplasmic point mutations (two point heteroplasmies found in mother and resolved to homoplasmy in children; three point heteroplasmies found in children only). The full fixation of the mutant variant within one or two generations in the North Atlantic right whale, Eubalaena glacialis , resulting in different haplotypes between siblings, has been identified by McLeod and White [11]. Finally, Santos et al [8] studied 48 human pedigrees (422 individuals) corresponding to 321 mtDNA transmissions and identified both shifts (up to ~40% change in heteroplasmic proportions) in some pedigrees as well as an apparently stable pattern of heteroplasmy in other pedigrees.…”

“…For a neutral mitochondrial heteroplasmic variant, the time to fixation has been estimated to be approximately 200 generations in humans and chinook salmon [2]. However, there have been cases reporting extremely fast fixation of heteroplasmic point mutations, within a few generations (e.g., [10, 11]) and in an extreme case in one generation [12]. The rapid segregation of haplotypes is thought to be generated by a bottleneck during oogenesis or embryogenesis reducing the number of mtDNA molecules, leading to random genetic drift [13–15].…”

“…Also, in other animal species, very few studies [11, 42] have evaluated how heteroplasmy levels vary among related individuals and between generations (but see, e.g., [8, 43] for studies in humans). This is probably because samples from far-related specimens or family/pedigree information are not available in most animal species.…”