Insight into the Peopling of Mainland Southeast Asia from Thai Population Genetic Structure

There is considerable ethno-linguistic and genetic variation among human populations in Asia, although tracing the origins of this diversity is complicated by migration events. Thailand is at the center of Mainland Southeast Asia (MSEA), a region within Asia that has not been extensively studied. Genetic substructure may exist in the Thai population, since waves of migration from southern China throughout its recent history may have contributed to substantial gene flow. Autosomal SNP data were collated for 438,503 markers from 992 Thai individuals. Using the available self-reported regional origin, four Thai subpopulations genetically distinct from each other and from other Asian populations were resolved by Neighbor-Joining analysis using a 41,569 marker subset. Using an independent Principal Components-based unsupervised clustering approach, four major MSEA subpopulations were resolved in which regional bias was apparent. A major ancestry component was common to these MSEA subpopulations and distinguishes them from other Asian subpopulations. On the other hand, these MSEA subpopulations were admixed with other ancestries, in particular one shared with Chinese. Subpopulation clustering using only Thai individuals and the complete marker set resolved four subpopulations, which are distributed differently across Thailand. A Sino-Thai subpopulation was concentrated in the Central region of Thailand, although this constituted a minority in an otherwise diverse region. Among the most highly differentiated markers which distinguish the Thai subpopulations, several map to regions known to affect phenotypic traits such as skin pigmentation and susceptibility to common diseases. The subpopulation patterns elucidated have important implications for evolutionary and medical genetics. The subpopulation structure within Thailand may reflect the contributions of different migrants throughout the history of MSEA. The information will also be important for genetic association studies to account for population-structure confounding effects.     

Origins of weedy rice revealed by polymorphisms of chloroplast DNA sequences and nuclear microsatellites

Conspecific weeds that permanently infest worldwide agroecosystems are evolved from their crop species. These weeds cause substantial problems for crop production by competing for resources in agricultural fields. Weedy rice represents such a conspecific weed infesting rice ecosystems, and causing tremendous rice yield losses owing to its strong competitiveness and abundant genetic diversity, likely resulted from its complex origins. Here, we report the use of chloroplast DNA (cpDNA) fingerprints to determine whether weedy rice is evolved from its wild (exo‐feral) or cultivated (endo‐feral) rice progenitor as the maternal donor in recent hybridization events. In addition, we also applied nuclear simple sequence repeat (SSR) markers to confirm the exo‐feral or endo‐feral origins of weedy rice accessions determined by the cpDNA fingerprints. We found that the studied weedy rice accessions evolved either from their wild or cultivated rice progenitor, as the maternal donor, based on the cpDNA network and structure analyses. Combined analyses of cpDNA and nuclear SSR markers indicated that a much greater proportion of weedy rice accessions had the endo‐feral origin. In addition, results from the genetic structure of nuclear SSR markers indicated that weedy rice accessions from the endo‐feral pathway are distinctly associated with either indica or japonica rice cultivars, suggesting their complex origins through crop–weed introgression. The complex pathways of origin and evolution could greatly promote genetic diversity of weedy rice. Therefore, innovative methods should be developed for effective weedy rice control.     

A triple-isotope approach to predict the breeding origins of European bats

Despite a commitment by the European Union to protect its migratory bat populations, conservation efforts are hindered by a poor understanding of bat migratory strategies and connectivity between breeding and wintering grounds. Traditional methods like mark-recapture are ineffective to study broad-scale bat migratory patterns. Stable hydrogen isotopes (δD) have been proven useful in establishing spatial migratory connectivity of animal populations. Before applying this tool, the method was calibrated using bat samples of known origin. Here we established the potential of δD as a robust geographical tracer of breeding origins of European bats by measuring δD in hair of five sedentary bat species from 45 locations throughout Europe. The δD of bat hair strongly correlated with well-established spatial isotopic patterns in mean annual precipitation in Europe, and therefore was highly correlated with latitude. We calculated a linear mixed-effects model, with species as random effect, linking δD of bat hair to precipitation δD of the areas of hair growth. This model can be used to predict breeding origins of European migrating bats. We used δ(13)C and δ(15)N to discriminate among potential origins of bats, and found that these isotopes can be used as variables to further refine origin predictions. A triple-isotope approach could thereby pinpoint populations or subpopulations that have distinct origins. Our results further corroborated stable isotope analysis as a powerful method to delineate animal migrations in Europe.     

The positioning and dynamics of origins of replication in the budding yeast nucleus

We have analyzed the subnuclear position of early- and late-firing origins of DNA replication in intact yeast cells using fluorescence in situ hybridization and green fluorescent protein (GFP)-tagged chromosomal domains. In both cases, origin position was determined with respect to the nuclear envelope, as identified by nuclear pore staining or a NUP49-GFP fusion protein. We find that in G1 phase nontelomeric late-firing origins are enriched in a zone immediately adjacent to the nuclear envelope, although this localization does not necessarily persist in S phase. In contrast, early firing origins are randomly localized within the nucleus throughout the cell cycle. If a late-firing telomere-proximal origin is excised from its chromosomal context in G1 phase, it remains late-firing but moves rapidly away from the telomere with which it was associated, suggesting that the positioning of yeast chromosomal domains is highly dynamic. This is confirmed by time-lapse microscopy of GFP-tagged origins in vivo. We propose that sequences flanking late-firing origins help target them to the periphery of the G1-phase nucleus, where a modified chromatin structure can be established. The modified chromatin structure, which would in turn retard origin firing, is both autonomous and mobile within the nucleus.     

Refugial isolation and secondary contact in the dyeing poison frog Dendrobates tinctorius

Recent palaeoclimactic research suggests that fluctuating environmental conditions throughout the Pleistocene of Amazonia occurred with previously unrecognized frequency. This has resulted in a theoretical shift from glacially influenced fluctuations to those driven by precessional rhythms. This theoretical revolution has a profound impact on expectations of biotic diversity within biogeographical regions that have long been based on the idea of large-scale landscape fragmentation associated with increased aridity and glacial cycles. Generally speaking, this shifts phylogeographical expectations from that of (i) large areas of sympatry of closely related (but not sister) species whose origins lie in separate refugia, and current distributions are the results of cyclic connectivity of those two refugia (refuge hypothesis), to that of (ii) fine scale genetic structure, often associated with elevation, and divergence well below expected speciation levels [disturbance-vicariance (DV) hypothesis]. To date there have been few tests of the expectations of the DV hypothesis based on empirical studies of Neotropical floral and faunal communities. Herein we examine phylogeographical structure of Dendrobates tinctorius, an amphibian species endemic to the uplands of the eastern Guiana Shield, based on sampling of 114 individuals from 24 localities. Phylogenetic, nested clade, and dispersal-vicariance (DIVA) analyses of cytochrome b sequence data reveal the presence of two mitochondrial lineages that are associated with previously identified western and eastern uplands of this area. The geographical distribution of mitochondrial haplotypes and the results of DIVA and coalescent analyses suggest that there has been extensive secondary contact between these lineages indicating a complex history of connectivity between these western and eastern highlands, supporting the predictions of the DV hypothesis.     

Origins and complexes: the initiation of DNA replication

Eukaryotic DNA is organized for replication as multiple replicons. DNA synthesis in each replicon is initiated at an origin of replication. In both budding yeast, Saccharomyces cerevisiae and fission yeast, Schizosaccharomyces pombe, origins contain specific sequences that are essential for initiation, although these differ significantly between the two yeasts with those of S. pombe being more complex then those of S. cerevisiae. However, it is not yet clear whether the replication origins of plants contain specific essential sequences or whether origin sites are determined by features of chromatin structure. In all eukaryotes there are several biochemical events that must take place before initiation can occur. These are the marking of the origins by the origin recognition complex (ORC), the loading onto the origins, in a series of steps, of origin activation factors including the MCM proteins, and the initial denaturation of the double helix to form a replication "bubble". Only then can the enzymes that actually initiate replication, primase and DNA polymerase-alpha, gain access to the template. In many cells this complex series of events occurs only once per cell cycle, ensuring that DNA is not re-replicated within one cycle. However, regulated re-replication of DNA within one cell cycle (DNA endoreduplication) is relatively common in plants, indicating that the "once-per-cycle" controls can be overridden.     

Assembly of the brainstem cochlear nuclear complex is revealed by intersectional and subtractive genetic fate maps

The cochlear nuclear complex (CN) is the entry point for central auditory processing. Although constituent neurons have been studied physiologically, their embryological origins and molecular profiles remain obscure. Applying intersectional and subtractive genetic fate mapping approaches, we show that this complex develops modularly from genetically separable progenitor populations arrayed as rostrocaudal microdomains within and outside the hindbrain (lower) rhombic lip (LRL). The dorsal CN subdivision, structurally and topographically similar to the cerebellum, arises from microdomains unexpectedly caudal and noncontiguous to cerebellar primordium; ventral CN subdivisions arise from more rostral LRL. Magnocellular regions receive contributions from LRL and coaxial non-lip progenitors; contrastingly, ensheathing granule cells derive principally from LRL. Also LRL-derived and molecularly similar to CN granule cells are precerebellar mossy fiber neurons; surprisingly, these ostensibly intertwined populations have separable origins and adjacent but segregated migratory streams. Together, these findings provide new platforms for investigating the development and evolution of auditory and cerebellar systems.     

Genome-wide characterization of fission yeast DNA replication origins

Eukaryotic DNA replication is initiated from multiple origins of replication, but little is known about the global regulation of origins throughout the genome or in different types of cell cycles. Here, we identify 401 strong origins and 503 putative weaker origins spaced in total every 14 kb throughout the genome of the fission yeast Schizosaccharomyces pombe. The same origins are used during premeiotic and mitotic S-phases. We found that few origins fire late in mitotic S-phase and that activating the Rad3 dependent S-phase checkpoint by inhibiting DNA replication had little effect on which origins were fired. A genome-wide analysis of eukaryotic origin efficiencies showed that efficiency was variable, with large chromosomal domains enriched for efficient or inefficient origins. Average efficiency is twice as high during mitosis compared with meiosis, which can account for their different S-phase lengths. We conclude that there is a continuum of origin efficiency and that there is differential origin activity in the mitotic and meiotic cell cycles.     

Requirements for species-specific papovavirus DNA replication.

Replication of papovavirus DNA requires a functional replication origin, a virus-encoded protein, large T antigen, and species-specific permissive factors. How these components interact to initiate and sustain viral DNA replication is not known. Toward that end, we have attempted to identify the viral target(s) of permissive factors. The functionally defined replication origins of polyomavirus and simian virus 40, two papovaviruses that replicate in different species (mice and monkeys, respectively), are composed of two functionally distinct domains: a core domain and an auxiliary domain. The origin cores of the two viruses are remarkably similar in primary structure and have common binding sites for large T antigen. By contrast, their auxiliary domains share few sequences and serve as binding sites for cellular proteins. It seemed plausible, therefore, that if cellular permissive factors interacted with the replication origin, their targets were likely to be in the auxiliary domain. To test this hypothesis we constructed hybrid origins for DNA replication that were composed of the auxiliary domain of one virus and the origin core of the other and assessed their capacity to replicate in a number of mouse and monkey cell lines, which express the large T antigen of one or the other virus. The results of this analysis showed that the auxiliary domains of the viral replication origins could substitute for one another in DNA replication, provided that the viral origin core and its cognate large T antigen were present in a permissive cellular milieu. Surprisingly, the large T antigens of the viruses could not substitute for one another, regardless of the species of origin of the host cell, even though the two large T antigens bind to the same sequence motif in vitro. These results suggest that species-specific permissive factors do not interact with the origin-auxiliary domains but, rather, with either the origin core or the large T antigen or with both components to effect DNA replication.     

More than multiple introductions: Multiple taxa contribute to the genesis of the invasive California’s wild artichoke thistle

The history of some invasive species is so complex that their origins can be difficult to determine. One example of such invasive species is the California invasive known as “wild artichoke thistle” (Cynara cardunculus var. sylvestris), found in natural and disturbed ecosystems. Wild artichoke thistle is a Mediterranean native and the progenitor of two domesticated horticultural taxa, artichoke and cardoon. Different hypotheses regarding the origins of California plants have included introductions by 19th century Italian immigrants and the de-domestication (evolutionary reversion to wild-type morphology) of feral (escaped, free-living) cultivars. Using microsatellite markers, we compared the genetic constitutions of 12 artichoke thistle populations in California with possible progenitor populations: 17 Spanish and Italian wild populations and eight different artichoke and cardoon cultivars. Each California population was compared with its putative progenitors using STRUCTURE analysis. Our results suggest that California's artichoke thistle populations are polyphyletic. Surprisingly, two-thirds of California's populations closely matched populations from the Iberian Peninsula. Three populations matched domesticated artichoke. One population appears to have wild and cultivar hybrid ancestry. Alleles specific to Italian populations were found at low frequencies in some California plants, suggesting that Italian wild plants may have been in California, but have left a trivial genetic legacy. Given that the de-domesticated plants in this study appear to be as invasive as the wild taxon, we conclude with a discussion of the role that ferality and de-domestication may have in plant invasions.     

An ARS element inhibits DNA replication through a SIR2-dependent mechanism

During G1 phase, a prereplicative complex (pre-RC) that determines where DNA synthesis initiates forms at origins. The Sir2p histone deacetylase inhibits pre-RC assembly at a subset of origins, suggesting that Sir2p inhibits DNA replication through a unique aspect of origin structure. Here, we identified five SIR2-sensitive origins on chromosomes III and VI. Linker scan analysis of two origins indicated that they share a common organization, including an inhibitory sequence positioned 3' to the sites of origin recognition complex (ORC) binding and pre-RC assembly. This inhibitory sequence (I(S)) required SIR2 for its activity, suggesting that SIR2 inhibits origins through this sequence. Furthermore, I(S) elements occurred within positioned nucleosomes, and Abf1p-mediated exclusion of nucleosomes from the origin abrogated the inhibition. These data suggest that Sir2p and I(S) elements inhibit origin activity by promoting an unfavorable chromatin structure for pre-RC assembly.     

DNA replication origins fire stochastically in fission yeast

DNA replication initiates at discrete origins along eukaryotic chromosomes. However, in most organisms, origin firing is not efficient; a specific origin will fire in some but not all cell cycles. This observation raises the question of how individual origins are selected to fire and whether origin firing is globally coordinated to ensure an even distribution of replication initiation across the genome. We have addressed these questions by determining the location of firing origins on individual fission yeast DNA molecules using DNA combing. We show that the firing of replication origins is stochastic, leading to a random distribution of replication initiation. Furthermore, origin firing is independent between cell cycles; there is no epigenetic mechanism causing an origin that fires in one cell cycle to preferentially fire in the next. Thus, the fission yeast strategy for the initiation of replication is different from models of eukaryotic replication that propose coordinated origin firing.     

Polymorphic Alu insertions and their associations with MHC class I alleles and haplotypes in Han and Jinuo populations in Yunnan Province, southwest of China

The associations of polymorphic Alu insertions （POALINs） with major histocompatibility complex （MHC） class I genes enable us to better identify origins and evolution of MHC class I region haplotypes in different populations. For further studying origins and evolution of MHC class I region haplotypes in Han and Jinuo populations in Yunnan Province, we investigated frequencies of five POALINs, their associations with HLA-A and -B, the three-loci POALINs haplotype frequencies and HLA/POALIN four-loci haplotype frequencies within the alpha block of MHC class I region. We found that a strong positive association between AluHG and HLA-A＊02 is in Jinuo, but not in Yunnan Han. These results suggest that MHC class I region haplotypes of the two studied populations might derive from different progenitor haplotypes and MHC I-POALINs are informative genetic markers for investigating origins and evolution of MHC class I region haplotypes in different populations.     

Analysis of digital patterns in the Basque valley of Deba: multivariate comparison with other populations

Eighty-six females and 79 males from the Basque valley of Deba were analyzed with respect to their digital patterns using correspondence analysis. We found that there was a significant sexual difference for only one type of pattern, tented arch. Also, this population was compared with other Basque valley populations and with other Spanish populations. We found great variability among Basque subpopulations, despite their supposed common origin. Dermatoglyphic distances for some traits can be interpreted as genetic distances because there is high heritability of these traits. The results of the comparison between the Deba valley population and other Spanish populations showed that the Deba population is markedly distant from the other populations.