Mitonuclear Coevolution, but Not Nuclear Compensation, Drives Evolution of OXPHOS Complexes in Bivalves

In Metazoa, 4 out of 5 complexes involved in oxidative phosphorylation (OXPHOS) are formed by subunits encoded by both the mitochondrial (mtDNA) and nuclear (nuDNA) genomes, leading to the expectation of mito-nuclear coevolution. Previous studies have supported co-adaptation of mitochondria-encoded (mtOXPHOS) and nuclear-encoded OXPHOS (nuOXPHOS) subunits, often specifically interpreted with regard to the “nuclear compensation hypothesis”, a specific form of mitonuclear coevolution where nuclear genes compensate for deleterious mitochondrial mutations owing to less efficient mitochondrial selection. In this study we analysed patterns of sequence evolution of 79 OXPHOS subunits in 31 bivalve species, a taxon showing extraordinary mtDNA variability and including species with “doubly uniparental” mtDNA inheritance. Our data showed strong and clear signals of mitonuclear coevolution. NuOXPHOS subunits had concordant topologies with mtOXPHOS subunits, contrary to previous phylogenies based on nuclear genes lacking mt interactions. Evolutionary rates between mt and nuOXPHOS subunits were also highly correlated compared to non-OXPHOS-interacting nuclear genes. Nuclear subunits of chimeric OXPHOS complexes (I, III, IV, and V) also had higher dN/dS ratios than Complex II, which is formed exclusively by nuDNA-encoded subunits. However, we did not find evidence of nuclear compensation: mitochondria-encoded subunits showed similar dN/dS ratios compared to nuclear-encoded subunits, contrary to most previously studied bilaterian animals. Moreover, no site-specific signals of compensatory positive selection were detected in nuOXPHOS genes. Our analyses extend the evidence for mitonuclear coevolution to a new taxonomic group, but we propose a reconsideration of the nuclear compensation hypothesis.

Mitochondrial genome and risk of multiple sclerosis

Mitochondrial DNA (mtDNA) polymorphism makes a certain contribution to the formation of a genetic risk of multiple sclerosis (MS).Objective: to analyze the frequency of mtDNA variants in patients with MS and control individuals in the Russian population. A similar study was conducted for the first time.Patients and methods. The polymorphism of mtDNA was studied in the Russian population: in 283 unrelated patients with relapsing-remitting MS and in 290 unrelated healthy controls matched for gender and age.Results and discussion. The frequency of haplogroup J in the patients with MS was twice higher than that in the control group (p=0.0055) (odds ratio (OR) 2.00; 95% confidence interval (CI). 1.21–3.41). This association was mostly observed in women (p=0.0083) (OR 2.20; 95% CI, 1.19–4.03). There was also a significant association of the A allele of MT-ND5 (m. 13708G>A) with MS (p=0.03) (OR 1.89; 95% CI 1.11–3.32). Sex stratification showed that the association with MS was significant only in women (p=0.009; OR, 2.52; 95% CI, 1.29–5.14). Further investigations will aim to analyze mtDNA variability (at the level of individual polymorphisms, haplogroups, and whole genome) in patients with relapsing-remitting MS and in those with primary progressive MS versus healthy individuals and patients with relapsing-remitting MS according to disease severity.Conclusion. The data obtained in the Russian population suggest that mtDNA variations are involved in MS risk, to a greater extent in women.

The Sicilian wolf: Genetic identity of a recently extinct insular population

During historical times many local grey wolf (Canis lupus) populations underwent a substantial reduction of their sizes or became extinct. Among these, the wolf population once living in Sicily, the biggest island of the Mediterranean Sea, was completely eradicated by human persecution in the early decades of the XX century.In order to understand the genetic identity of the Sicilian wolf, we applied ancient DNA techniques to analyse the mitochondrial DNA of six specimens actually stored in Italian museums.We successfully amplified a diagnostic mtDNA fragment of the control region (CR) in four of the samples. Results showed that two samples shared the same haplotype, that differed by two substitutions from the currently most diffused Italian wolf haplotype (W14) and one substitution from the only other Italian haplotype (W16). The third sample showed a wolf-like haplotype never described before and the fourth a haplotype commonly found in dogs.Furthermore, all the wolf haplotypes detected in this study belonged to the mitochondrial haplogroup that includes haplotypes detected in all the known European Pleistocene wolves and in several modern southern European populations.Unfortunately, this endemic island population, bearing unique mtDNA variability, was definitively lost before it was possible to understand its taxonomic uniqueness and conservational value.

Family-specific vs. universal PCR primers for the study of mitochondrial DNA in plants

Mitochondrial genomes (mtDNAs or mitogenomes) of seed plants are characterized by a notoriously unstable organization on account of which available so-called universal or consensus primers may fail to fulfil their foreseen function - amplification of various mtDNA regions in a broad range of plant taxa. Thus, the primers developed for groups assumed to have similar organization of their mitogenomes, such as families, may facilitate a broader usage of more variable non-coding portions of these genomes in group members. Using in silico PCR method and six available complete mitogenomes of Fabaceae, it has been demonstrated that only three out of 36 published universal primer and three Medicago sativa-specific primer pairs that amplify various mtDNA regions are suitable for six representatives of the Fabaceae family upon minor modifications, and develop 21 Fabaceae-specific primer pairs for amplification of all 14 cis-splicing introns in genes of NADH subunits (nad genes) which represent the most commonly used non-coding mtDNA regions in various studies in plants. Using the same method and six available complete mitogenomes of representatives of related families Cucurbitaceae, Euphorbiaceae and Rosaceae and a model plant, Arabidopsis thaliana, it has further been demonstrated that applicability of newly developed primer pairs for amplification of nad introns in more or less related taxa was dependent not only on species evolutionary distances but also on their genome sizes. A reported set of 24 primer pairs is a valuable resource which may facilitate a broader usage of mtDNA variability in future studies at both intra- and inter-specific levels in Fabaceae, which is the third largest family of flowering plants rarely studied at the mtDNA level, and in other more or less related taxa.