Knowledge about the world phylogeny of human mitochondrial DNA (mtDNA) is essential not only for evaluating the pathogenic role of specific mtDNA mutations but also for performing reliable association studies between mtDNA haplogroups and complex disorders. In the past few years, the main features of the East Asian portion of the mtDNA phylogeny have been determined on the basis of complete sequencing efforts, but representatives of several basal lineages were still lacking. Moreover, some recently published complete mtDNA sequences did apparently not fit into the known phylogenetic tree and conflicted with the established nomenclature. To refine the East Asian mtDNA tree and resolve data conflicts, we first completely sequenced 20 carefully selected mtDNAs--likely representatives of novel sub-haplogroups--and then, in order to distinguish diagnostic mutations of novel haplogroups from private variants, we applied a 'motif-search' procedure to a large sample collection. The novel information was incorporated into an updated East Asian mtDNA tree encompassing more than 1000 (near-) complete mtDNA sequences. A reassessment of the mtDNA data from a series of disease studies testified to the usefulness of such a refined mtDNA tree in evaluating the pathogenicity of mtDNA mutations. In particular, the claimed pathogenic role of mutations G3316A, T3394C, A4833G and G15497A appears to be most questionable as those initial claims were derived from anecdotal findings rather than e.g. appropriate association studies. Following a guideline based on the phylogenetic knowledge as proposed here could help avoiding similar problems in the future.

The Northwestern Pacific has a unique tectonic and geographical history with several marginal seas separating Asia from the Pacific Ocean. During low sea level periods of Pleistocene glaciations, populations might have been isolated in three marginal seas: the Sea of Japan, East China Sea and South China Sea. Following postglacial sea level rise, we would expect the populations isolated in the three regions to have been homogenized by high dispersal potential. To assess these hypotheses, we explore the intraspecific phylogeographical patterns in redlip mullet, Chelon haematocheilus. Fragments of 435 bp at the 5' end of mitochondrial DNA control region were sequenced for 272 individuals from nine localities over most of the species' range. Three distinct lineages were detected, which might have diverged in the three marginal seas during Pleistocene low sea levels. Contrary to homogenization expectation, there were strong differences in the geographical distribution of the three lineages. Analyses of molecular variance and the population statistic Phi(ST) also revealed significant genetic structure among populations of the three marginal seas. These results indicate that gene flow in Chelon haematocheilus is far more restricted spatially than predicted by the potential dispersal capabilities of this species. The lack of phylogeographical structure in East China Sea may reflect a recent range expansion after the last glacial maximum and insufficient time to attain migration-drift equilibrium.

Constitutive ablation of the Yin Yang 1 (YY1) transcription factor in mice results in peri-implantation lethality. In this study, we used homologous recombination to generate knockout mice carrying yy1 alleles expressing various amounts of YY1. Phenotypic analysis of yy1 mutant embryos expressing ϳ75%, ϳ50%, and ϳ25% of the normal complement of YY1 identified a dosage-dependent requirement for YY1 during late embryogenesis. Indeed, reduction of YY1 levels impairs embryonic growth and viability in a dose-dependent manner. Analysis of the corresponding mouse embryonic fibroblast cells also revealed a tight correlation between YY1 dosage and cell proliferation, with a complete ablation of YY1 inducing cytokinesis failure and cell cycle arrest. Consistently, RNA interference-mediated inhibition of YY1 in HeLa cells prevents cytokinesis, causes proliferative arrest, and increases cellular sensitivity to various apoptotic agents. Genome-wide expression profiling identified a plethora of YY1 target genes that have been implicated in cell growth, proliferation, cytokinesis, apoptosis, development, and differentiation, suggesting that YY1 coordinates multiple essential biological processes through a complex transcriptional network. These data not only shed new light on the molecular basis for YY1 developmental roles and cellular functions, but also provide insight into the general mechanisms controlling eukaryotic cell proliferation, apoptosis, and differentiation.Regulation of fundamental cellular processes such as homeostasis, growth, proliferation, apoptosis, and differentiation involves complex networks of transcription factors as well as chromatin-remodeling proteins. Dysregulation of a wide variety of transcriptional regulators has been linked to various developmental defects and diseases, such as tumorigenesis.Yin Yang 1 (YY1; also called delta, NF-E1, and UCRBP) is a ubiquitously expressed GLI-Krüppel zinc finger-containing transcription factor (23,28,44,60). It is highly conserved from Xenopus to humans and has been shown to be the vertebrate homolog of the Drosophila melanogaster polycomb group protein Pleiohomeotic (2, 16, 64). YY1 is a multifunctional protein which can act as a transcriptional repressor or activator through combinatorial interactions with various other transcription factors, coactivators, and corepressors as well as chromatin-remodeling complexes displaying opposite functions, including the histone acetyltransferase p300/CBP, the arginine methyltransferase PRMT1, and the histone deacetylases HDAC1 and HDAC2 (4,[9][10][11][12]26,34,35,45,47,57,62,65,80,82,83).Since its original isolation, YY1 has been shown to control an ever-growing number of viral and cellular genes, among which are the human immunodeficiency virus type 1 and human papillomavirus oncogenes E6 and E7, several proto-oncogenes (c-myc, c-fos, and errb2), cdc-6 (cell division cycle 6 homolog), the DNA replication-dependent histone H3.2 gene, as well as various others (53,59,68,76). With a few exceptions, many YY1 target genes hav...

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Due to its numerous environmental extremes, the Tibetan Plateau-the world's highest plateau-is one of the most challenging areas of modern human settlement. Archaeological evidence dates the earliest settlement on the plateau to the Late Paleolithic, while previous genetic studies have traced the colonization event(s) to no earlier than the Neolithic. To explore whether the genetic continuity on the plateau has an exclusively Neolithic time depth, we studied mitochondrial DNA (mtDNA) genome variation within 6 regional Tibetan populations sampled from Tibet and neighboring areas. Our results confirm that the vast majority of Tibetan matrilineal components can trace their ancestry to Epipaleolithic and Neolithic immigrants from northern China during the midHolocene. Significantly, we also identified an infrequent novel haplogroup, M16, that branched off directly from the Eurasian M founder type. Its nearly exclusive distribution in Tibetan populations and ancient age (>21 kya) suggest that M16 may represent the genetic relics of the Late Paleolithic inhabitants on the plateau. This partial genetic continuity between the Paleolithic inhabitants and the contemporary Tibetan populations bridges the results and inferences from archaeology, history, and genetics.mtDNA ͉ origin

Much like other indigenous domesticated animals, Tibetan chickens living at high altitudes (2,200-4,100 m) show specific physiological adaptations to the extreme environmental conditions of the Tibetan Plateau, but the genetic bases of these adaptations are not well characterized. Here, we assembled a de novo genome of a Tibetan chicken and resequenced whole genomes of 32 additional chickens, including Tibetan chickens, village chickens, game fowl, and Red Junglefowl, and found that the Tibetan chickens could broadly be placed into two groups. Further analyses revealed that several candidate genes in the calcium-signaling pathway are possibly involved in adaptation to the hypoxia experienced by these chickens, as these genes appear to have experienced directional selection in the two Tibetan chicken populations, suggesting a potential genetic mechanism underlying high altitude adaptation in Tibetan chickens. The candidate selected genes identified in this study, and their variants, may be useful targets for clarifying our understanding of the domestication of chickens in Tibet, and might be useful in current breeding efforts to develop improved breeds for the highlands.

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Overexploitation, habitat destruction, human-driven climate change and disease spread are resulting in the extinction of innumerable species, with amphibians being hit harder than most other groups [1]. Few species of amphibians are widespread, and those that are often represent complexes of multiple cryptic species. This is especially true for range-restricted salamanders [2]. Here, we used the widespread and critically endangered Chinese giant salamander (Andrias davidianus) to show how genetically uninformed management efforts can negatively affect species conservation. We find that this salamander consists of at least five species-level lineages. However, the extensive recent translocation of individuals between farms, where the vast majority of extant salamanders now live, has resulted in genetic homogenization. Mitochondrial DNA (mtDNA) haplotypes from northern China now predominate in farms. Unfortunately, hybrid offspring are being released back into the wild under well-intentioned, but misguided, conservation management. Our findings emphasize the necessity of genetic assessments for seemingly well-known, widespread species in conservation initiatives. Species serve as the primary unit for protection and management in conservation actions [3], so determining the taxonomic status of threatened species is a major concern, especially for amphibians. The level of threat to amphibians may be underestimated, and existing conservation strategies may be inadvertently harmful if conducted without genetic assessment.