Differentiation of mitochondrial DNA and Y chromosomes in Russian populations

The genetic composition of the Russian population was investigated by analyzing both mitochondrial DNA (mtDNA) and Y-chromosome loci polymorphisms that allow for the different components of a population gene pool to be studied, depending on the mode of DNA marker inheritance. mtDNA sequence variation was examined by using hypervariable segment I (HVSI) sequencing and restriction analysis of the haplogroup-specific sites in 325 individuals representing 5 Russian populations from the European part of Russia. The Y-chromosome variation was investigated in 338 individuals from 8 Russian populations (including 5 populations analyzed for mtDNA variation) using 12 binary markers. For both uniparental systems most of the observed haplogroups fell into major West Eurasian haplogroups (97.9% and 99.7% for mtDNA and Y-chromosome haplogroups, respectively). Multidimensional scaling analysis based on pairwise F(ST) values between mtDNA HVSI sequences in Russians compared to other European populations revealed a considerable heterogeneity of Russian populations; populations from the southern and western parts of Russia are separated from eastern and northern populations. Meanwhile, the multidimensional scaling analysis based on Y-chromosome haplogroup F(ST) values demonstrates that the Russian gene pool is close to central-eastern European populations, with a much higher similarity to the Baltic and Finno-Ugric male pools from northern European Russia. This discrepancy in the depth of penetration of mtDNA and Y-chromosome lineages characteristic for the most southwestern Russian populations into the east and north of eastern Europe appears to indicate that Russian colonization of the northeastern territories might have been accomplished mainly by males rather than by females.     

Investigation of genetic factors influencing duration of copulation in "eastern" and "western" Drosophila athabasca.

Observations of mating behaviour were made on "eastern" and "western" Drosophila athabasca and on flies of mixed genetic background. Duration of copulation in mixed combinations of D. athabasca is determined by the male. In F1 males the source of X-chromosome, whether eastern or western, partly determined suration of copulation. However, durations of copulation of backcross males suggest autosomal influence, in that males derived from an eastern backcross demonstrate significantly shorter durations than males derived from a western backcross. In addition, durations of copulation from F2 combinations exhibit greater variance than the F1 and thereby represent evidence of F2 segregation.     

Contrasting signatures of population growth for mitochondrial DNA and Y chromosomes among human populations in Africa

A history of Pleistocene population expansion has been inferred from the frequency spectrum of polymorphism in the mitochondrial DNA (mtDNA) of many human populations. Similar patterns are not typically observed for autosomal and X-linked loci. One explanation for this discrepancy is a recent population bottleneck, with different rates of recovery for haploid and autosomal loci as a result of their different effective population sizes. This hypothesis predicts that mitochondrial and Y chromosomal DNA will show a similar skew in the frequency spectrum in populations that have experienced a recent increase in effective population size. We test this hypothesis by resequencing 6.6 kb of noncoding Y chromosomal DNA and 780 basepairs of the mtDNA cytochrome c oxidase subunit III (COIII) gene in 172 males from 5 African populations. Four tests of population expansion are employed for each locus in each population: Fu's Fs statistic, the R(2) statistic, coalescent simulations, and the mismatch distribution. Consistent with previous results, patterns of mtDNA polymorphism better fit a model of constant population size for food-gathering populations and a model of population expansion for food-producing populations. In contrast, none of the tests reveal evidence of Y chromosome growth for either food-gatherers or food-producers. The distinct mtDNA and Y chromosome polymorphism patterns most likely reflect sex-biased demographic processes in the recent history of African populations. We hypothesize that males experienced smaller effective population sizes and/or lower rates of migration during the Bantu expansion, which occurred over the last 5,000 years.     

Ancestry of the Iban is predominantly Southeast Asian: genetic evidence from autosomal, mitochondrial, and Y chromosomes

Humans reached present-day Island Southeast Asia (ISEA) in one of the first major human migrations out of Africa. Population movements in the millennia following this initial settlement are thought to have greatly influenced the genetic makeup of current inhabitants, yet the extent attributed to different events is not clear. Recent studies suggest that south-to-north gene flow largely influenced present-day patterns of genetic variation in Southeast Asian populations and that late Pleistocene and early Holocene migrations from Southeast Asia are responsible for a substantial proportion of ISEA ancestry. Archaeological and linguistic evidence suggests that the ancestors of present-day inhabitants came mainly from north-to-south migrations from Taiwan and throughout ISEA approximately 4,000 years ago. We report a large-scale genetic analysis of human variation in the Iban population from the Malaysian state of Sarawak in northwestern Borneo, located in the center of ISEA. Genome-wide single-nucleotide polymorphism (SNP) markers analyzed here suggest that the Iban exhibit greatest genetic similarity to Indonesian and mainland Southeast Asian populations. The most common non-recombining Y (NRY) and mitochondrial (mt) DNA haplogroups present in the Iban are associated with populations of Southeast Asia. We conclude that migrations from Southeast Asia made a large contribution to Iban ancestry, although evidence of potential gene flow from Taiwan is also seen in uniparentally inherited marker data.     

Differences in ribosomal DNA distribution on A and B chromosomes between eastern and western populations of the grasshopper Eyprepocnemis plorans plorans

Distribution of ribosomal DNA (rDNA) on standard (A) and supernumerary (B) chromosomes of the grasshopper Eyprepocnemis plorans was analysed in specimens collected in Turkey and Armenia, belonging to the E. p. plorans subspecies, and in South Africa, belonging to the E. p. meridionalis subspecies. The latter individuals showed rDNA loci in chromosomes 9 and 11 only, whereas those from Armenia carried it in chromosomes 9 and 11 or else in chromosomes 9-11, depending on the population. The specimens from Turkey carried it in chromosomes 1, 9-11 and X. A comparison of this pattern with those previously observed in populations from Spain, Morocco, and Greece (belonging to E. p. plorans) suggests the existence of two evolutionary patterns in rDNA chromosome location in A chromosomes of this subspecies: eastern populations showing rDNA restricted to the small (9-11) chromosomes (as in E. p. meridionalis and other closely related taxa within the Eyprepocneminae subfamily) and western populations carrying rDNA in most A chromosomes (Spain) or all of them (Morocco). The intermediate pattern discerned in geographically intermediate populations (in Greece and Turkey), with rDNA also being located on the X chromosome, suggests a possible east-west cline. Additional support for east-west differentiation in the rDNA location pattern comes from the analysis of B chromosomes. In eastern populations, including Daghestan, Armenia, Turkey, and Greece, B chromosomes are composed mostly of rDNA, whereas in western populations (Spain and Morocco) they contain roughly similar amounts of rDNA and a 180-bp tandem repeat (satDNA), the latter being scarce in eastern Bs.     

Scale-specific sex-biased dispersal in the Valais shrew unveiled by genetic variation on the Y chromosome, autosomes, and mitochondrial DNA

We investigated sex specificities in the evolutionary processes shaping Y chromosome, autosomes, and mitochondrial DNA patterns of genetic structure in the Valais shrew (Sorex antinorii), a mountain dwelling species with a hierarchical distribution. Both hierarchical analyses of variance and isolation-by-distance analyses revealed patterns of population structure that were not consistent across maternal, paternal, and biparentally inherited markers. Differentiation on a Y microsatellite was lower than expected from the comparison with autosomal microsatellites and mtDNA, and it was mostly due to genetic variance among populations within valleys, whereas the opposite was observed on other markers. In addition, there was no pattern of isolation by distance for the Y, whereas there was strong isolation by distance on mtDNA and autosomes. We use a hierarchical island model of coancestry dynamics to discuss the relative roles of the microevolutionary forces that may induce such patterns. We conclude that sex-biased dispersal is the most important driver of the observed genetic structure, but with an intriguing twist: it seems that dispersal is strongly male biased at large spatial scale, whereas it is mildly biased in favor of females at local scale. These results add to recent reports of scale-specific sex-biased dispersal patterns, and emphasize the usefulness of the Y chromosome in conjunction with mtDNA and autosomes to infer sex specificities.     

Mitochondrial DNA in the Atlantic cod, Gadus morhua: lack of genetic divergence between eastern and western populations

Mitochondrial DNA variation was examined in two populations of Atlantic cod from the North Sea and the Grand Banks of Newfoundland. Eight restriction enzymes revealed no major genetic difference between these eastern and western populations. These results are discussed in relation to earlier electrophoretic studies on this species.     

The genetic localization of presumptive mitochondrial messenger RNAs on rat-liver mitochondrial DNA.

High molecular weight mitochondrial (mt) RNAs were isolated from rat liver mitochondria and hybridized in the presence of excess competitor mt rRNA and/or mt tRNA to restriction fragments of mtDNA. The data reveals that there are a few areas of the mt-genome on which the complementary of these presumptive messenger RNAs is most pronounced. These areas are away from the parts of the genome which are coding for the mt rRNA or containing the D-loop.     

Homologies between X and Y chromosomes detected by DNA probes: localisation and evolution.

We have isolated and characterized DNA probes that detect homologies between the X and Y chromosomes. Clone St25 is derived from the q13-q22 region of the X chromosome and recognizes a 98% homologous sequence on the Y chromosome. Y specific fragments were present in DNAs from 5 Yq-individuals and from 4 out of 7 XX males analysed. An X linked TaqI RFLP is detected with the St25 probe (33% heterozygosity) which should allow one to establish a linkage map including other polymorphic X-Y homologous sequences in this region and to compare it to a Y chromosome deletion map. Probe DXS31 located in Xp223-pter detects a 80% homologous sequence in the Y chromosome. The latter can be assigned to Yq11-qter outside the region which contains the Y specific satellite sequences. ACT1 and ACT2, the actin sequences present on the X and Y chromosomes respectively, have been cloned. No homology was detected between the X and Y derived fragments outside from the actin sequence. ACT2 and the Y specific sequence corresponding to DXS31 segregate together in a panel of Y chromosomes aberrations, and might be useful markers for the region important for spermatogenesis in Yq. Various primate species were analysed for the presence of sequences homologous to the three probes. Sequences detected by St25 and DXS31 are found only on the X chromosome in cercopithecoidae. The sequences which flank ACT2 detect in the same species autosomal fragments but no male specific fragments. It is suggested that the Y chromosome acquired genetic material from the X chromosome and from autosomes at various times during primate evolution.     

The mitochondrial genome is a "genetic sanctuary" during the oncogenic process

Since Otto Warburg linked mitochondrial physiology and oncogenesis in the 1930s, a number of studies have focused on the analysis of the genetic basis for the presence of aerobic glycolysis in cancer cells. However, little or no evidence exists today to indicate that mtDNA mutations are directly responsible for the initiation of tumor onset. Based on a model of gliomagenesis in the mouse, we aimed to explore whether or not mtDNA mutations are associated with the initiation of tumor formation, maintenance and aggressiveness. We reproduced the different molecular events that lead from tumor initiation to progression in the mouse glioma. In human gliomas, most of the genetic alterations that have been previously identified result in the aberrant activation of different signaling pathways and deregulation of the cell cycle. Our data indicates that mitochondrial dysfunction is associated with reactive oxygen species (ROS) generation, leading to increased nuclear DNA (nDNA) mutagenesis, but maintaining the integrity of the mitochondrial genome. In addition, mutational stability has been observed in entire mtDNA of human gliomas; this is in full agreement with the results obtained in the cancer mouse model. We use this model as a paradigm of oncogenic transformation due to the fact that mutations commonly found in gliomas appear to be the most common molecular alterations leading to tumor development in most types of human cancer. Our results indicate that the mtDNA genome is kept by the cell as a "genetic sanctuary" during tumor development in the mouse and humans. This is compatible with the hypothesis that the mtDNA molecule plays an essential role in the control of the cellular adaptive survival response to tumor-induced oxidative stress. The integrity of mtDNA seems to be a necessary element for responding to the increased ROS production associated with the oncogenic process.     

Stochasticity overrules the "three-times rule": genetic drift,genetic draft,and coalescence times for nuclear loci versus mitochondrial DNA

Abstract.— Palumbi et al. (2001) proposed a "three-times rule" that uses mitochondrial DNA (mtDNA) sequences to predict probabilities of monophyly for nuclear loci (i.e., whether the alleles within a taxon coalesce with one another before they coalesce with alleles from a sister taxon). They use neutral coalescent theory to infer these probabilities from the ratio of interspecific divergence to intraspecific variation of mtDNA. We show that the estimated probabilities have very wide confidence intervals because of the inherent stochasticity of the mtDNA coalescent process. Under neutrality, the true probability of monophyly can be much higher, or much lower, than predicted by the three-times rule. We also review recent empirical and theoretical studies that refute neutrality-based predictions concerning mtDNA variation and divergence. We conclude that the three-times rule is neither a useful test for neutral molecular evolution nor a reliable guide to genealogical species.     

Molecular genetic evidence for the human settlement of the Pacific: analysis of mitochondrial DNA, Y chromosome and HLA markers

Present-day Pacific islanders are thought to be the descendants of Neolithic agriculturalists who expanded from island South-east Asia several thousand years ago. They speak languages belonging to the Austronesian language family, spoken today in an area spanning half of the circumference of the world, from Madagascar to Easter Island, and from Taiwan to New Zealand. To investigate the genetic affinities of the Austronesian-speaking peoples, we analysed mitochondrial DNA, HLA and Y-chromosome polymorphisms in individuals from eight geographical locations in Asia and the Pacific (China, Taiwan, Java, New Guinea highlands, New Guinea coast, Trobriand Islands, New Britain and Western Samoa). Our results show that the demographic expansion of the Austronesians has left a genetic footprint. However, there is no simple correlation between languages and genes in the Pacific.     

Variation in mitochondrial DNA and post-glacial colonization of north western Europe by brown trout

A purified mitochondrial DNA (mtDNA) probe was used to examine restriction fragment length polymorphisms produced by six restriction enzymes ( Xba I, Eco RV, Ava II, Hinf I, Hae III, Mbo I) in 915 brown trout from western Europe. A total of 20 composite haplotypes were found with one to seven haplotypes in individual populations. Icelandic trout samples from north, south, east, and west coast drainages showed only a single common haplotype in contrast to the high level of polymorphism found in Irish and Scottish populations. The phylogeny of mtDNA haplotypes and the pattern of haplotype distribution suggests that post-glacial colonization of brown trout in NW Europe was more complex than the dual colonization model which has been proposed on the basis of differential LDH-5* allele distribution. For example, Lough Melvin (Ireland) appears to have been independently     

The distribution of mitochondrial DNA heteroplasmy due to random genetic drift

Cells containing pathogenic mutations in mitochondrial DNA (mtDNA) generally also contain the wild-type mtDNA, a condition called heteroplasmy. The amount of mutant mtDNA in a cell, called the heteroplasmy level, is an important factor in determining the amount of mitochondrial dysfunction and therefore the disease severity. mtDNA is inherited maternally, and there are large random shifts in heteroplasmy level between mother and offspring. Understanding the distribution in heteroplasmy levels across a group of offspring is an important step in understanding the inheritance of diseases caused by mtDNA mutations. Previously, our understanding of the heteroplasmy distribution has been limited to just the mean and variance of the distribution. Here we give equations, adapted from the work of Kimura on random genetic drift, for the full mtDNA heteroplasmy distribution. We describe how to use the Kimura distribution in mitochondrial genetics, and we test the Kimura distribution against human, mouse, and Drosophila data sets.     

Out of Arabia—The settlement of Island Soqotra as revealed by mitochondrial and Y chromosome genetic diversity

The Soqotra archipelago is one of the most isolated landmasses in the world, situated at the mouth of the Gulf of Aden between the Horn of Africa and southern Arabia. The main island of Soqotra lies not far from the proposed southern migration route of anatomically modern humans out of Africa ～60,000 years ago (kya), suggesting the island may harbor traces of that first dispersal. Nothing is known about the timing and origin of the first Soqotri settlers. The oldest historical visitors to the island in the 15th century reported only the presence of an ancient population. We collected samples throughout the island and analyzed mitochondrial DNA and Y‐chromosomal variation. We found little African influence among the indigenous people of the island. Although the island population likely experienced founder effects, links to the Arabian Peninsula or southwestern Asia can still be found. In comparison with datasets from neighboring regions, the Soqotri population shows evidence of long‐term isolation and autochthonous evolution of several mitochondrial haplogroups. Specifically, we identified two high‐frequency founder lineages that have not been detected in any other populations and classified them as a new R0a1a1 subclade. Recent expansion of the novel lineages is consistent with a Holocene settlement of the island ～6 kya. Am J Phys Anthropol, 2009. © 2008 Wiley‐Liss, Inc.     

Native American Y chromosomes in Polynesia: the genetic impact of the Polynesian slave trade

Since Thor Heyerdahl asserted that Polynesia was first colonized from the Americas (Heyerdahl 1950), geneticists have sought--but have not found--any evidence to support his theories. Here, Native American Y chromosomes are detected on the Polynesian island of Rapa. However, this, together with other odd features of the island's Y-chromosomal gene pool, is best explained as the genetic impact of a 19th century Peruvian slave trade in Polynesia. These findings underscore the need to account for history before turning to prehistory and the value of archival research to understanding modern genetic diversity. Although the impact of the Atlantic slave trade on the distribution of modern genetic diversity has been well appreciated, this represents the first study investigating the impact of this underappreciated episode on genetic diversity in the Pacific.     

The origin and genetic relationships of the Baikal seal, Phoca sibirica, by restriction analysis of mitochondrial DNA

The origin and genetic relationships of the Baikal seal, Phoca sibirica, were studied by restriction fragment length polymorphism analysis of mitochondrial DNA (mtDNA). Using 17 different six-base recognition restriction endonucleases, we examined 98 Baikal seals, and two other related species, the ringed seal, P. hispida, (n=87), and the Caspian seal, P. caspica, (n=94). Analysis revealed the existence of 87 mtDNA haplotypes in the total of 279 specimens. The haplotypes of each species were divided into different clusters on a dendrogram obtained by UPGMA based on haplotype frequency and mtDNA base substitution. No common haplotypes were found among the species examined. The Baikal seal is much more closely related to the ringed seal than the Caspian seal. The amount of divergence suggested that an ancestor of the Baikal seal came down to the lake approximately 0.4 million years ago as was previously indicated by paleontological studies. The seals examined here showed lower variabilities.