Duplication of the mitochondrial control region is associated with increased longevity in birds.
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ABSTRACT:
SUBMITTER: Skujina I
PROVIDER: S-EPMC5032695 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Previous work compared frequency of longevity-associated polymorphisms (LAPS) in long-lived individuals and in controls from the general population (primarily in Europe and Japan), suggesting the polymorphisms are responsible for unusual longevity. However, individuals from the general population are not the control group for long-lived subjects because both were born in different periods. We report results of a project which collected mtDNA from living subjects in Costa Rica, and traced back their maternal genealogy. Since mtDNA does not recombine and its probability of mutation is low, we can assume that the maternal ancestors had the same mtDNA of their descendants. We compared the longevity of individuals with LAPS with the longevity of controls born in the same time period. We did not confirm previous associations for several markers, but found that the 5178A mutation in haplogroup D is associated with decreased longevity, whereas the 150T mutation is associated with increased longevity. These associations however, are not significant for all time periods under study. While our data confirm that mtDNA make up affects longevity, they also indicate that the time period in which a person was born had a much greater impact on longevity than presence or absence of a marker.
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Project description:Brain size of vertebrates has long been recognized to evolve in close association with basic life-history traits, including lifespan. According to the cognitive buffer hypothesis, large brains facilitate the construction of behavioral responses against novel socioecological challenges through general cognitive processes, which should reduce mortality and increase lifespan. While the occurrence of brain size-lifespan correlation has been well documented in mammals, much less evidence exists for a robust link between brain size and longevity in birds. The aim of this study was to use phylogenetically controlled comparative approach to test for the relationship between brain size and longevity among 384 avian species from 23 orders. We used maximum lifespan and maximum reproductive lifespan as the measures of longevity and accounted for a set of possible confounding effects, such as allometry, sampling effort, geographic patterns, and life-history components (clutch size, incubation length, and mode of development). We found that both measures of longevity positively correlated with relative (residual) brain size. We also showed that major diversification of brain size preceded diversification of longevity in avian evolution. In contrast to previous findings, the effect of brain size on longevity was consistent across lineages with different development patterns, although the relatively low strength of this correlation could likely be attributed to the ubiquity of allomaternal care associated with the altricial mode of development. Our study indicates that the positive relationship between brain size and longevity in birds may be more general than previously thought.
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Project description:The links between energy expenditure and ageing are different at different levels of enquiry. When studies have examined the relationships between different species within a given class the association is generally negative--animals with greater metabolism per gram of tissue live shorter lives. Within species, or between classes (e.g. between birds and mammals) the association is the opposite--animals with higher metabolic rates live longer. We have previously shown in mammals that the negative association between lifespan and metabolic rate is in fact an artefact of using resting rather than daily energy expenditure, and of failing to adequately take into account the confounding effects of body size and the lack of phylogenetic independence of species data. When these factors are accounted for, across species of mammals, the ones with higher metabolism also have the largest lifetime expenditures of energy-consistent with the inter-class and intra-specific data. A previous analysis in birds did not yield the same pattern, but this may have been due to a lack of sufficient power in the analysis. Here we present an analysis of a much enlarged data set (>300 species) for metabolic and longevity traits in birds. These data show very similar patterns to those in mammals. Larger individuals have longer lives and lower per-gram resting and daily energy expenditures, hence there is a strong negative relationship between longevity and mass-specific metabolism. This relationship disappears when the confounding effects of body mass and phylogeny are accounted for. Across species of birds, lifetime expenditure of energy per gram of tissue based on both daily and resting energy expenditure is positively related to metabolic intensity, mirroring these statistical relationships in mammals and synergizing with the positive associations of metabolism with lifespan within species and between vertebrate classes.
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Project description:Sociality, as a life-history trait, should be associated with high longevity because complex sociality is characterized by reproductive suppression, delayed breeding, increased care and survival, and some of these traits select for high longevity. We studied the relationship between cooperative parental care (a proxy of complex sociality) and relative maximum lifespan in 257 North American bird species. After controlling for variation in maximum lifespan explained by body mass, sampling effort, latitude, mortality rate, migration distance and age at first reproduction, we found no significant effect of cooperative care on longevity in analyses of species-specific data or phylogenetically independent standardized linear contrasts. Thus, sociality itself is not associated with high longevity. Rather, longevity is correlated with increased body size, survival rate and age of first reproduction.
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Project description:PURPOSE:Polymorphisms in the control region of mitochondrial DNA (mtDNA) can affect generation of reactive oxygen species and impact in the pathogenesis of endometriosis. This study investigated the association of mtDNA polymorphisms with endometriosis. METHODS:Patients were divided in two groups: endometriosis (n = 90) and control (n = 92). Inclusion criteria were as follows: women between 18 and 50 years, with histological diagnosis and surgical staging of endometriosis (endometriosis group) or undergoing gynecological surgery for tubal ligation, leiomyoma, or ovarian cysts, with no evidence of endometriosis (control group). DNA extraction was performed from peripheral blood. Sanger sequencing of mtDNA control region was performed, and polymorphisms were determined comparing the sequences obtained with the Cambridge Reference Sequence. RESULTS:The frequency of polymorphisms T16217C (14.4 and 5.4% of endometriosis and control group, respectively; p = 0.049) and G499A (13.3 vs. 4.3%; p = 0.038) was higher in the endometriosis group, while T146C (32.6 vs. 18.9%; p = 0.042) and 573.2C (5.6 vs. 29.3%; p < 0.001) were lower. No difference was observed in haplogroups between groups. CONCLUSION:mtDNA polymorphisms T16217C and G499A were associated with endometriosis, while T416C and 573.2C were shown to be associated with an absence of disease.
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Project description:Platysternon megacephalum is the sole living representative of the poorly studied turtle lineage Platysternidae. Their mitochondrial genome has been subject to gene rearrangement and control region duplication, resulting in a unique mitochondrial gene order in vertebrates. In this study, we sequenced the first full-length turtle (P. megacephalum) liver transcriptome using single-molecule real-time sequencing to study the transcriptional mechanisms of its mitochondrial genome. ND5 and ND6 anti-sense (ND6AS) forms a single transcript with the same expression in the human mitochondrial genome, but here we demonstrated differential expression of the rearranged ND5 and ND6AS genes in P. megacephalum. And some polycistronic transcripts were also reported in this study. Notably, we detected some novel long non-coding RNAs with alternative polyadenylation from the duplicated control region, and a novel ND6AS transcript composed of a long non-coding sequence, ND6AS, and tRNA-GluAS. These results provide the first description of a mtDNA transcriptome with gene rearrangement and control region duplication. These findings further our understanding of the fundamental concepts of mitochondrial gene transcription and RNA processing, and provide a new insight into the mechanism of transcription regulation of the mitochondrial genome.
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Project description:The nuo-6 and isp-1 genes of C. elegans encode, respectively, subunits of complex I and III of the mitochondrial respiratory chain. Partial loss-of-function mutations in these genes decrease electron transport and greatly increase the longevity of C. elegans by a mechanism that is distinct from that induced by reducing their level of expression by RNAi. Electron transport is a major source of the superoxide anion (O(?) (-)), which in turn generates several types of toxic reactive oxygen species (ROS), and aging is accompanied by increased oxidative stress, which is an imbalance between the generation and detoxification of ROS. These observations have suggested that the longevity of such mitochondrial mutants might result from a reduction in ROS generation, which would be consistent with the mitochondrial oxidative stress theory of aging. It is difficult to measure ROS directly in living animals, and this has held back progress in determining their function in aging. Here we have adapted a technique of flow cytometry to directly measure ROS levels in isolated mitochondria to show that the generation of superoxide is elevated in the nuo-6 and isp-1 mitochondrial mutants, although overall ROS levels are not, and oxidative stress is low. Furthermore, we show that this elevation is necessary and sufficient to increase longevity, as it is abolished by the antioxidants NAC and vitamin C, and phenocopied by mild treatment with the prooxidant paraquat. Furthermore, the absence of effect of NAC and the additivity of the effect of paraquat on a variety of long- and short-lived mutants suggest that the pathway triggered by mitochondrial superoxide is distinct from previously studied mechanisms, including insulin signaling, dietary restriction, ubiquinone deficiency, the hypoxic response, and hormesis. These findings are not consistent with the mitochondrial oxidative stress theory of aging. Instead they show that increased superoxide generation acts as a signal in young mutant animals to trigger changes of gene expression that prevent or attenuate the effects of subsequent aging. We propose that superoxide is generated as a protective signal in response to molecular damage sustained during wild-type aging as well. This model provides a new explanation for the well-documented correlation between ROS and the aged phenotype as a gradual increase of molecular damage during aging would trigger a gradually stronger ROS response.
| S-EPMC2998438 | biostudies-literature
Project description:BackgroundMultipartite mitochondrial genomes are very rare in animals but have been found previously in two insect orders with highly rearranged genomes, the Phthiraptera (parasitic lice), and the Psocoptera (booklice/barklice).ResultsWe provide the first report of a multipartite mitochondrial genome architecture in a third order with highly rearranged genomes: Thysanoptera (thrips). We sequenced the complete mitochondrial genomes of two divergent members of the Scirtothrips dorsalis cryptic species complex. The East Asia 1 species has the single circular chromosome common to animals while the South Asia 1 species has a genome consisting of two circular chromosomes. The fragmented South Asia 1 genome exhibits extreme chromosome size asymmetry with the majority of genes on the large, 14.28 kb, chromosome and only nad6 and trnC on the 0.92 kb mini-circle chromosome. This genome also features paralogous control regions with high similarity suggesting a very recent origin of the nad6 mini-circle chromosome in the South Asia 1 cryptic species.ConclusionsThysanoptera, along with the other minor paraenopteran insect orders should be considered models for rapid mitochondrial genome evolution, including fragmentation. Continued use of these models will facilitate a greater understanding of recombination and other mitochondrial genome evolutionary processes across eukaryotes.
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Project description:Telomeres, the terminal repetitive DNA sequences at the ends of linear chromosomes, have strong associations with longevity in some major taxa. Longevity has been linked to rate of decline in telomere length in birds and mammals, and absolute telomere length seems to be associated with body mass in mammals. Using a phylogenetic comparative method and 30 species of birds, we examined longevity (reflected by maximum lifespan), absolute telomere length, the rate of change in telomere length (TROC), and body mass (often strongly associated with longevity) to ascertain their degree of association. We divided lifespan into two life-history components, one reflected by body size (measured as body mass) and a component that was statistically independent of body mass. While both lifespan and body mass were strongly associated with a family tree of the species (viz., the phylogeny of the species), telomere measures were not. Telomere length was not significantly associated with longevity or body mass or our measure of mass-independent lifespan. TROC, however, was strongly associated with mass-independent lifespan, but only to a much lesser degree at best with body mass-predicted lifespan. Our results supported an association of TROC and longevity, in particular longevity that was independent of body size and part of the pace-of-life syndrome of life histories.
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Project description:Using a very high-resolution oligonucleotide array for copy number variant (CNV) screening of samples comprising schizophrenic patients, we detected a novel CNV within the critical region (NCBI36/hg18, Chr7: 158,630,410-158,719,410) previously shown to be associated with schizophrenia. We investigated the association between the novel CNV identified in the current study and schizophrenia. Three independent samples were used: (1) Screening set, 300 Japanese schizophrenic patients (53.28 ± 14.66 years); (2) Confirmation set, 531 schizophrenic patients (46.03 ± 12.15 years); and (3) 711 healthy controls (47.12 ± 11.03 years). All subjects enrolled in the study were Japanese. Chromosomal position was determined using fluorescence in situ hybridization. We identified a novel duplication within the region associated with schizophrenia identified on 7q36.3 that is adjacent to VIPR2 and is not associated with schizophrenia. In the Japanese population, the 35-kb region that harbors the common, novel CNV should be excluded from the region associated with schizophrenia on 7q36.3.
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