Climate shaped the worldwide distribution of human mitochondrial DNA sequence variation

There is an ongoing discussion in the literature on whether human mitochondrial DNA (mtDNA) evolves neutrally. There have been previous claims for natural selection on human mtDNA based on an excess of non-synonymous mutations and higher evolutionary persistence of specific mitochondrial mutations in Arctic populations. However, these findings were not supported by the reanalysis of larger datasets. Using a geographical framework, we perform the first direct test of the relative extent to which climate and past demography have shaped the current spatial distribution of mtDNA sequences worldwide. We show that populations living in colder environments have lower mitochondrial diversity and that the genetic differentiation between pairs of populations correlates with difference in temperature. These associations were unique to mtDNA; we could not find a similar pattern in any other genetic marker. We were able to identify two correlated non-synonymous point mutations in the ND3 and ATP6 genes characterized by a clear association with temperature, which appear to be plausible targets of natural selection producing the association with climate. The same mutations have been previously shown to be associated with variation in mitochondrial pH and calcium dynamics. Our results indicate that natural selection mediated by climate has contributed to shape the current distribution of mtDNA sequences in humans.     

Pathogenetic mechanisms in hereditary dysfunctions of complex I of the respiratory chain in neurological diseases

This paper covers genetic and biochemical aspects of mitochondrial bioenergetics dysfunction in hereditary neurological disorders associated with complex I defects. Three types of hereditary complex I dysfunction are dealt with: (i) homozygous mutations in the nuclear genes NDUFS1 and NDUFS4 of complex I, associated with mitochondrial encephalopathy; (ii) a recessive hereditary epileptic neurological disorder associated with enhanced proteolytic degradation of complex I; (iii) homoplasmic mutations in the ND5 and ND6 mitochondrial genes of the complex, cohexistent with mutation in the nuclear PINK1 gene in familial Parkinsonism. The genetic and biochemical data examined highlight different mechanisms by which mitochondrial bioenergetics is altered in these hereditary defects of complex I. This knowledge, besides clarifying molecular aspects of the pathogenesis of hereditary diseases, can also provide hints for understanding the involvement of complex I in sporadic neurological disorders and aging, as well as for developing therapeutical strategies.     

Mitochondrial DNA mutation m.3635G>A may be associated with Leber hereditary optic neuropathy in Chinese

Leber hereditary optic neuropathy (LHON) was the first disease to be linked to the presence of a mitochondrial DNA (mtDNA) mutation. Nowadays over 95% of LHON cases are known to be caused by one of three primary mutations (m.11778G>A, m.14484T>C, and m.3460G>A). Reports for other (rare) primary mutations in LHON patients are not infrequent. Among those is the mutation m.3635G>A in the MT-ND1 gene which was reported to be pathogenic in a Russian LHON family. In this study, we report on a Chinese family with clinical features of LHON but without any of the three well-known primary mutations. Analysis of the complete mitochondrial genome in the proband revealed the presence of m.3635G>A and m.6228C>T, along with a full array of other variants that suggest the haplogroup M7b1. Evolutionary analysis indicates that site 3635, but not 6228, is highly conserved in vertebrates. Protein secondary-structure modeling for the MT-ND1 protein harboring amino acid change S110N indicates that mutant m.3635G>A decreases the protein hydrophobicity. Our current observations provide further support for a pathogenic role of m.3635G>A in patients with LHON.     

Novel A14841G mutation is associated with high penetrance of LHON/C4171A family

We report the clinical and genetic characterization of a Chinese LHON family carrying an ND1/C4171A mutation. This family has high penetrance of visual impairment and extremely low frequency of vision recovery, which is in marked contrast to previously reported results for Korean LHON families with the same mutation. Sequence analysis of the complete mtDNA in the partially defined East Asian haplogroup N9a1 revealed the presence of 29 other variants. A novel heteroplasmic A14841G mutation, one of the variants with a serine substituted for a highly conserved asparagine at amino acid 32 of Cytochrome b (Cytb), may play a synergistic role with the C4171A mutation, leading to significantly different clinical manifestations of LHON among these families. The study further confirmed that C4171A was a rare primary LHON mutation, and the mtDNA background could also contribute to the clinical manifestation of the LHON/C4171A mutation.     

Extra‐mitochondrial localization and likely reproductive function of a female‐transmitted cytochrome c oxidase subunit II protein

Our previous study documented a reproductive function for the male‐transmitted mitochondrial DNA (mtDNA)‐encoded cytochrome c oxidase subunit II (MCOX2) protein in a unionoid bivalve. Here, immunoblotting, immunohistochemistry and immunoelectron microscopy analyses demonstrate that the female‐transmitted protein (FCOX2) is: (i) expressed in both male and female gonads; (ii) maximally expressed in ovaries just prior to the time of the annual fertilization event; (iii) displayed in the cytoplasm and more strongly in the plasma membrane (microvilli), vitelline matrix and vitelline envelope of mature ovarian eggs; and (iv) strongly localized to the vitelline matrix of some eggs just prior to fertilization. These findings represent evidence for the extra‐mitochondrial localization of an mtDNA‐encoded gene product and are consistent with multifunctionality for FCOX2 in eggs.     

Mitochondrial DNA variation in the caramote prawn <Emphasis Type="Italic">Penaeus (Melicertus) kerathurus</Emphasis> across a transition zone in the Mediterranean Sea

In this study we analysed mitochondrial DNA variation in Penaeus kerathurus prawns collected from seven locations along a transect across the Siculo–Tunisian region in order to verify if any population structuring exists over a limited geographical scale and to delineate the putative transition zone with sufficient accuracy. Partial DNA sequences of COI and 16S genes were analysed. In contrast to the highly conservative 16S gene, the COI sequences exhibited sufficient diversity for population analysis. The COI gene revealed low levels of haplotype and nucleotide diversities. The size of the annual landings of this commercial species suggests large population sizes. Hence, the low genetic diversity detected in this study could indicate a possible reduction in effective population sizes in the past. We detected significant genetic differentiation between eastern and western populations likely due to restricted gene flow across the Siculo–Tunisian boundary. We discuss the different evolutionary forces that may have shaped the genetic variation and suggest that the genetic divide is probably maintained by present-day dispersal limitation. R. Zitari-Chatti and N. Chatti are contributed equally to the work.     

Unwinding by Local Strand Separation Is Critical for the Function of DEAD-Box Proteins as RNA Chaperones

The DEAD-box proteins CYT-19 in Neurospora crassa and Mss116p in Saccharomyces cerevisiae are broadly acting RNA chaperones that function in mitochondria to stimulate group I and group II intron splicing and to activate mRNA translation. Previous studies showed that the S. cerevisiae cytosolic/nuclear DEAD-box protein Ded1p could stimulate group II intron splicing in vitro. Here, we show that Ded1p complements mitochondrial translation and group I and group II intron splicing defects in mss116Δ strains, stimulates the in vitro splicing of group I and group II introns, and functions indistinguishably from CYT-19 to resolve different nonnative secondary and/or tertiary structures in the Tetrahymena thermophila large subunit rRNA-ΔP5abc group I intron. The Escherichia coli DEAD-box protein SrmB also stimulates group I and group II intron splicing in vitro, while the E. coli DEAD-box protein DbpA and the vaccinia virus DExH-box protein NPH-II gave little, if any, group I or group II intron splicing stimulation in vitro or in vivo. The four DEAD-box proteins that stimulate group I and group II intron splicing unwind RNA duplexes by local strand separation and have little or no specificity, as judged by RNA-binding assays and stimulation of their ATPase activity by diverse RNAs. In contrast, DbpA binds group I and group II intron RNAs nonspecifically, but its ATPase activity is activated specifically by a helical segment of E. coli 23S rRNA, and NPH-II unwinds RNAs by directional translocation. The ability of DEAD-box proteins to stimulate group I and group II intron splicing correlates primarily with their RNA-unwinding activity, which, for the protein preparations used here, was greatest for Mss116p, followed by Ded1p, CYT-19, and SrmB. Furthermore, this correlation holds for all group I and group II intron RNAs tested, implying a fundamentally similar mechanism for both types of introns. Our results support the hypothesis that DEAD-box proteins have an inherent ability to function as RNA chaperones by virtue of their distinctive RNA-unwinding mechanism, which enables refolding of localized RNA regions or structures without globally disrupting RNA structure.     

Morphological and mtDNA sequence studies on three crucian carps (Carassius: Cyprinidae) including a new stock from the Ob River system, Kazakhstan

Three morphologically and genetically distinct forms of the genus Carassius were collected from the Ob River system, Kazakhstan, Central Asia; Carassius carassius , Carassius gibelio gibelio and an unknown stock tentatively referred to as Carassius gibelio sub-species M. The last mentioned had 33–41 gill rakers, being intermediate between the other two forms (23–27 in C. carassius and 44–49 in C. g. gibelio ), and five scales in the upper transverse series, less than in the others. It also had a relatively larger erythrocyte suggesting triploidy and an mtDNA haplotype distinct from all other known crucian carps. Comparative mtDNA phylogenetic analysis suggested that C. gibelio gibelio in the Ob River system was introduced from China and the Amur River, the same possibly being true for European C. gibelio gibelio based on published haplotypes. C. gibelio sub-species M is thought to be more widely distributed in central Asia, probably extending as far west as European Russia.     

Genetic evidence of two stocks of the whitemouth croaker Micropogonias furnieri in the Río de la Plata and oceanic front in Uruguay

Analysis of the mitochondrial DNA control region resolved two stocks of whitemouth croaker Micropogonias furnieri in Uruguayan waters, one in the Río de la Plata and the other on the Uruguayan shelf. The whitemouth croaker is the most important coastal fishery resource along the coast and has the greatest commercial importance in the Río de la Plata and its oceanic front. The number of pair-wise differences (π) and haplotype diversity ( h ) showed significant differences between the two regions. Frequencies of mtDNA haplotypes did not differ between Río de la Plata from Bahia Blanca M. furnieri . Samples from the oceanic front showed greater genetic variability and a larger effective number of females that were an order of magnitude larger than that in Río de la Plata. Mismatch distributions showed evidence of a recent population expansion in the oceanic region, beginning c. 40 000 b.p. The presence of two stocks of the M. furnieri in the study area should be considered in the management of this species' fishery.     

Phylogeographic distribution of mitochondrial DNA macrohaplogroup M in India

Indian subcontinent harbours both the human mtDNA macrohaplogroups M and N, of which M is the most prevalent. In this study, we discuss the overall distribution of the various haplogroups and sub-haplogroups of M among the different castes and tribes to understand their diverse pattern with respect to geographical location and linguistic affiliation of the populations. An overview of about 170 studied populations, belonging to four distinct linguistic families and inhabiting different geographic zones, revealed wide diversity of about 22 major haplogroups of M. The tribal populations belonging to the same linguistic family but inhabiting different geographical regions (Dravidian and Austro-Asiatic speakers) exhibited differences in their haplogroup diversity. The northern and southern region castes showed greater diversity than the castes of other regions.