Patterns Of DNA Sequence Variation Research Articles

Molecular phylogenetics shed light on polyploid speciation in gorses (Ulex, Fabaceae: Genisteae) and on the origin of the invasive Ulex europaeus

Abstract Hybridization and polyploidy are key evolutionary forces in plant diversification, and their co-occurrence in the context of allopolyploid speciation is often associated with increased ability to colonize new environments and invasiveness. In the genus Ulex (Fabaceae), the European gorse (Ulex europaeus subsp. europaeus) is the only invasive and the only polyploid that has recently spread in different eco-geographical regions across the world. Understanding what confers such ecological advantages to this species, compared to its diploid and polyploid congeners, first requires clarification of the ecogeographical and evolutionary context of its formation. To achieve this, the geographical distributions of all Ulex spp. were estimated from species occurrence records, and phylogenetic analyses including all Ulex spp. were performed based on four nuclear (ITS and ETS nrDNA) and plastid (rps12 intron and trnK-matK) regions. The resulting trees were dated using a secondary calibration. Patterns of DNA sequence variation and dated phylogenetic trees were then interpreted in light of previous knowledge of chromosome numbers in Ulex to infer past events of polyploid speciation in the genus. We show that: (1) most current Ulex spp. radiated in the Iberian Peninsula during the past 1–2 Myr; (2) the history of Ulex was punctuated by multiple whole-genome duplication events; and (3) U. europaeus subsp. europaeus is the only gorse taxon that was formed by hybridization of two well-differentiated lineages (which separated c. 5 Mya) with wide climatic ranges (currently represented by Ulex minor and Ulex europaeus subsp. latebracteatus), possibly contributing to the invasive nature and wider climatic range of U. europaeus subsp. europaeus. These findings provide a much-needed evolutionary framework in which to explore the adaptive consequences of genome mergers and duplication in Ulex.

Methods and models for unravelling human evolutionary history.

The genomes of contemporary humans contain considerable information about the history of our species. Although the general contours of human evolutionary history have been defined with increasing resolution throughout the past several decades, the continuing deluge of massively large sequencing data sets presents new opportunities and challenges for understanding human evolutionary history. Here, we review the signatures that demographic history imparts on patterns of DNA sequence variation, statistical methods that have been developed to leverage information contained in genome-scale data sets and insights gleaned from these studies. We also discuss the importance of using exploratory analyses to assess data quality, the strengths and limitations of commonly used population genomics methods, and factors that confound population genomics inferences.

Signals of Historical Interlocus Gene Conversion in Human Segmental Duplications

Standard methods of DNA sequence analysis assume that sequences evolve independently, yet this assumption may not be appropriate for segmental duplications that exchange variants via interlocus gene conversion (IGC). Here, we use high quality multiple sequence alignments from well-annotated segmental duplications to systematically identify IGC signals in the human reference genome. Our analysis combines two complementary methods: (i) a paralog quartet method that uses DNA sequence simulations to identify a statistical excess of sites consistent with inter-paralog exchange, and (ii) the alignment-based method implemented in the GENECONV program. One-quarter (25.4%) of the paralog families in our analysis harbor clear IGC signals by the quartet approach. Using GENECONV, we identify 1477 gene conversion tracks that cumulatively span 1.54 Mb of the genome. Our analyses confirm the previously reported high rates of IGC in subtelomeric regions and Y-chromosome palindromes, and identify multiple novel IGC hotspots, including the pregnancy specific glycoproteins and the neuroblastoma breakpoint gene families. Although the duplication history of a paralog family is described by a single tree, we show that IGC has introduced incredible site-to-site variation in the evolutionary relationships among paralogs in the human genome. Our findings indicate that IGC has left significant footprints in patterns of sequence diversity across segmental duplications in the human genome, out-pacing the contributions of single base mutation by orders of magnitude. Collectively, the IGC signals we report comprise a catalog that will provide a critical reference for interpreting observed patterns of DNA sequence variation across duplicated genomic regions, including targets of recent adaptive evolution in humans.

North Africans traveling north

Humans have always loved to move and to mate. In doing so, we generate complex patterns of diversity in language, custom, and culture across and within geographic regions. However, the richest and most durable signals of migration and admixture are evident in patterns of DNA sequence variation (1, 2). The study by Botigue et al. (3) reported in PNAS analyzes DNA sequence variation in Africa, the Near East, and Europe to advance our understanding of the peopling of Europe with a focus on the relatively recent contribution of North African ancestry to the contemporary population genetic structure of southern Europe.

Background Selection 20 Years on

The mutation process continually produces new deleterious variants at sites throughout the genome, which are then mostly eliminated by selection. This causes a reduction in variability at linked neutral or nearly neutral sites, as well as distortions of the genealogies of samples of alleles from a population. In regions of the genome where recombination is frequent, the effects of selection against deleterious mutations on variability and evolution at linked sites can be predicted under the assumption that most deleterious mutations have such large effects that their behavior in the population is effectively deterministic-this is background selection in the strict sense. But in genomic regions with little or no recombination, such as the Y chromosome, large departures from the predictions using deterministic models may occur, because of interference between different sites under selection. Evidence from Drosophila and human populations is discussed, which suggests that these processes play a major role in shaping patterns of DNA sequence variation and evolution, including the relative levels of variation on X chromosomes and autosomes, and the highly reduced variability seen in regions that lack crossing over.

Reduced Polymorphism Associated with X Chromosome Meiotic Drive in the Stalk-Eyed Fly Teleopsis dalmanni

Sex chromosome meiotic drive has been suggested as a cause of several evolutionary genetic phenomena, including genomic conflicts that give rise to reproductive isolation between new species. In this paper we present a population genetic analysis of X chromosome drive in the stalk-eyed fly, Teleopsis dalmanni, to determine how this natural polymorphism influences genetic diversity. We analyzed patterns of DNA sequence variation at two X-linked regions (comprising 1325 bp) approximately 50 cM apart and one autosomal region (comprising 921 bp) for 50 males, half of which were collected in the field from one of two allopatric locations and the other half were derived from lab-reared individuals with known brood sex ratios. These two populations are recently diverged but exhibit partial postzygotic reproductive isolation, i.e. crosses produce sterile hybrid males and fertile females. We find no nucleotide or microsatellite variation on the drive X chromosome, whereas the same individuals show levels of variation at autosomal regions that are similar to field-collected flies. Furthermore, one field-caught individual collected 10 years previously had a nearly identical X haplotype to the drive X, and is over 2% divergent from other haplotypes sampled from the field. These results are consistent with a selective sweep that has removed genetic variation from much of the drive X chromosome. We discuss how this finding may relate to the rapid evolution of postzygotic reproductive isolation that has been documented for these flies.

Higher differentiation among subspecies of the house mouse (Mus musculus) in genomic regions with low recombination

In the early stages of reproductive isolation, genomic regions of reduced recombination are expected to show greater levels of differentiation, either because gene flow between species is reduced in these regions or because the effects of selection at linked sites within species are enhanced in these regions. Here, we study the patterns of DNA sequence variation at 27 autosomal loci among populations of Mus musculus musculus, M. m. domesticus, and M. m. castaneus, three subspecies of house mice with collinear genomes. We found that some loci exhibit considerable shared variation among subspecies, while others exhibit fixed differences. We used an isolation-with-gene-flow model to estimate divergence times and effective population sizes (N(e) ) and to disentangle ancestral variation from gene flow. Estimates of divergence time indicate that all three subspecies diverged from one another within a very short period of time approximately 350,000 years ago. Overall, N(e) for each subspecies was associated with the degree of genetic differentiation: M. m. musculus had the smallest N(e) and the greatest proportion of monophyletic gene genealogies, while M. m. castaneus had the largest N(e) and the smallest proportion of monophyletic gene genealogies. M. m. domesticus and M. m. musculus were more differentiated from each other than either were from M. m. castaneus, consistent with greater reproductive isolation between M. m. domesticus and M. m. musculus. F(ST) was significantly greater at loci experiencing low recombination rates compared to loci experiencing high recombination rates in comparisons between M. m. castaneus and M. m. musculus or M. m. domesticus. These results provide evidence that genomic regions with less recombination show greater differentiation, even in the absence of chromosomal rearrangements.

Conflicting mitochondrial and nuclear phylogeographic signals and evolution of host-plant shifts in the boreo-montane leaf beetle Chrysomela lapponica

We conducted a phylogeographic study on the cold-adapted leaf beetle Chrysomela lapponica, that feeds on willow or birch, by sampling several populations throughout most of the geographic distribution of the species, and by sequencing for each individual one mitochondrial and two nuclear DNA fragments. Patterns of DNA sequence variation from the mitochondrial and nuclear loci, as displayed in the median-joining networks, appear to display contradicting historical signal: a deep genealogical divergence is observed with the mitochondrial genome between the Alpine population and all other populations found in the Euro-Siberian distribution of the species, that is completely absent with both nuclear loci. We use coalescence simulations of DNA sequence evolution to test the hypothesis that this apparent conflict is compatible with a neutral model of sequence evolution (i.e., to check whether the stochastic nature of the coalescence process can explain these patterns). Because the simulations show that this is highly unlikely, we consider two alternative hypotheses: (1) introgression of the mitochondrial genome of another species and (2) the effect of natural selection. Although introgression is the most plausible explanation, we fail to identify the source species of the introgressed mitochondrial genome among all known species closely related to C. lapponica. We therefore suggest that the putative introgression event is ancient and the source species is either extinct or currently outside the geographic range of C. lapponica explored in this study. The observed DNA sequence variation also suggests that a host-plant shift from willow to birch has occurred recently and independently in each of the three birch-feeding populations. This emphasizes further the relative ease with which these beetles can escape their ancestral host-plant specialization on willow, but shows at the same time that host-plant shifts are highly constrained, as they only occur between willow and birch.

Discovery of Pseudocalanus moultoni (Frost, 1989) in Northeast Atlantic waters based on mitochondrial COI sequence variation

The genus Pseudocalanus (Copepoda, Calanoida) consists of seven species, all of which are known to co-occur with two or more sibling species in some areas of their geographic ranges. Despite the ecological importance of this abundant genus, there is no available method that can reliably and accurately identify Pseudocalanus species without knowledge of origin. We present evidence of several observations of Pseudocalanus moultoni [Frost (1989) Can. J. Zool., 67, 525–551] in fjords of Svalbard and northern Norway; this species has previously been known to occur only on the east and west coasts of North America. Patterns of DNA sequence variation of the mitochondrial cytochrome oxidase subunit I (COI) gene allow us to confidently identify the species, discriminate it from co-occurring sibling species and infer relationships among the newly discovered and previously sampled P. moultoni populations. Our observations suggest that NE Atlantic populations of P. moultoni are self-sustaining and we discuss potential source populations and pathways of transport. In light of recent reports of climate-driven shifts in distributional ranges of marine zooplankton, accurate species identification is essential for monitoring and understanding marine ecosystems.

Rapid Rise and Fall of Selfish Sex-Ratio X Chromosomes in Drosophila simulans: Spatiotemporal Analysis of Phenotypic and Molecular Data

Sex-ratio drive, which has been documented in several Drosophila species, is induced by X-linked segregation distorters. Contrary to Mendel's law of independent assortment, the sex-ratio chromosome (X(SR)) is inherited by more than half the offspring of carrier males, resulting in a female-biased sex ratio. This segregation advantage allows X(SR) to spread in populations, even if it is not beneficial for the carriers. In the cosmopolitan species D. simulans, the Paris sex-ratio is caused by recently emerged selfish X(SR) chromosomes. These chromosomes have triggered an intragenomic conflict, and their propagation has been halted over a large area by the evolution of complete drive suppression. Previous molecular population genetics analyses revealed a selective sweep indicating that the invasion of X(SR) chromosomes was very recent in Madagascar (likely less than 100 years ago). Here, we show that X(SR) chromosomes are now declining at this location as well as in Mayotte and Kenya. Drive suppression is complete in the three populations, which display little genetic differentiation and share swept haplotypes, attesting to a common and very recent ancestry of the X(SR) chromosomes. Patterns of DNA sequence variation also indicate a fitness cost of the segmental duplication involved in drive. The data suggest that X(SR) chromosomes started declining first on the African continent, then in Mayotte, and finally in Madagascar and strongly support a scenario of rapid cycling of X chromosomes. Once drive suppression has evolved, standard X(ST) chromosomes locally replace costly X(SR) chromosomes in a few decades.

Patterns of DNA sequence variation at candidate gene loci in black poplar (Populus nigra L.) as revealed by single nucleotide polymorphisms

Black poplar (Populus nigra L.) is an economically and ecologically important tree species and an ideal organism for studies of genetic variation. In the present work, we use a candidate gene approach to infer the patterns of DNA variation in natural populations of this species. A total of 312 single nucleotide polymorphisms (SNPs) are found among 8,056 bp sequenced from nine drought-adaptation and photosynthesis-related gene loci. The median SNP frequency is one site per 26 bp. The average nucleotide diversity is calculated to be theta(W) = 0.01074 and pi(T) = 0.00702, higher values than those observed in P. tremula, P. trichocarpa and most conifer species. Tests of neutrality for each gene reveal a general excess of low-frequency mutations, a greater number of haplotypes than expected and an excess of high-frequency derived variants in P. nigra, which is consistent with previous findings that genetic hitchhiking has occurred in this species. Linkage disequilibrium is low, decaying rapidly from 0.45 to 0.20 or less within a distance of 300 bp, although the declines of r(2) are variable among different loci. This is similar to the rate of decay reported in most other tree species. Our dataset is expected to enhance understanding of how evolutionary forces shape genetic variation, and it will contribute to molecular breeding in black poplar.

Genetics of stroke

Stroke is the third leading cause of death and the leading cause of severe long-term disability in developed countries. Despite significant progress in understanding the risk factors conferring disease predisposition, the genetic and molecular basis of stroke remains poorly understood. Recent advances in the identification and characterization of patterns of DNA sequence variation in human populations hold the promise that stroke genomics will offer significant insights into disease pathophysiology and open new avenues for the development of novel therapeutic modalities. However, beyond single nucleotide polymorphisms, the emergence of additional sources of genomic variability as major factors in disease etiology is likely to transform our DNA-centric approaches toward more integrative and comprehensive strategies. This review provides an overview of the current progress and future prospects of the application of genomic sciences to stroke research.

Accelerated Adaptive Evolution on a Newly Formed X Chromosome

Sex chromosomes originated from ordinary autosomes, and their evolution is characterized by continuous gene loss from the ancestral Y chromosome. Here, we document a new feature of sex chromosome evolution: bursts of adaptive fixations on a newly formed X chromosome. Taking advantage of the recently formed neo-X chromosome of Drosophila miranda, we compare patterns of DNA sequence variation at genes located on the neo-X to genes on the ancestral X chromosome. This contrast allows us to draw inferences of selection on a newly formed X chromosome relative to background levels of adaptation in the genome while controlling for demographic effects. Chromosome-wide synonymous diversity on the neo-X is reduced 2-fold relative to the ancestral X, as expected under recent and recurrent directional selection. Several statistical tests employing various features of the data consistently identify 10%–15% of neo-X genes as targets of recent adaptive evolution but only 1%–3% of genes on the ancestral X. In addition, both the rate of adaptation and the fitness effects of adaptive substitutions are estimated to be roughly an order of magnitude higher for neo-X genes relative to genes on the ancestral X. Thus, newly formed X chromosomes are not passive players in the evolutionary process of sex chromosome differentiation, but respond adaptively to both their sex-biased transmission and to Y chromosome degeneration, possibly through demasculinization of their gene content and the evolution of dosage compensation.

Recent speciation associated with the evolution of selfing inCapsella

The evolution from outcrossing to predominant self-fertilization represents one of the most common transitions in flowering plant evolution. This shift in mating system is almost universally associated with the "selfing syndrome," characterized by marked reduction in flower size and a breakdown of the morphological and genetic mechanisms that prevent self-fertilization. In general, the timescale in which these transitions occur, and the evolutionary dynamics associated with the evolution of the selfing syndrome are poorly known. We investigated the origin and evolution of selfing in the annual plant Capsella rubella from its self-incompatible, outcrossing progenitor Capsella grandiflora by characterizing multilocus patterns of DNA sequence variation at nuclear genes. We estimate that the transition to selfing and subsequent geographic expansion have taken place during the past 20,000 years. This transition was probably associated with a shift from stable equilibrium toward a near-complete population bottleneck causing a major reduction in effective population size. The timing and severe founder event support the hypothesis that selfing was favored during colonization as new habitats emerged after the last glaciation and the expansion of agriculture. These results suggest that natural selection for reproductive assurance can lead to major morphological evolution and speciation on relatively short evolutionary timescales.

Detecting the Genetic Signature of Natural Selection in Human Populations: Models, Methods, and Data.

Patterns of DNA sequence variation in the genome contain a record of past selective events. The ability to collect increasingly large data sets of polymorphisms has allowed investigators to perform hypothesis-driven studies of candidate genes as well as genome-wide scans for signatures of adaptations. This genetic approach to the study of natural selection has identified many signals consistent with predictions from anthropological studies. Selective pressures related to variation in climate, diet, and pathogen exposure have left strong marks on patterns of human variation. Additional signals of adaptations are observed in genes involved in chemosensory perception and reproduction. Several ongoing projects aim to sequence the complete genome of 1000 individuals from different human populations. These large-scale projects will provide data for more complete genome scans of selection, but more focused studies aimed at testing specific hypotheses will continue to hold an important place in elucidating the history of adaptations in humans.

Effects of Spatially Varying Selection on Nucleotide Diversity and Linkage Disequilibrium: Insights From Deer Mouse Globin Genes

An important goal of population genetics is to elucidate the effects of natural selection on patterns of DNA sequence variation. Here we report results of a study to assess the joint effects of selection, recombination, and gene flow in shaping patterns of nucleotide variation at genes involved in local adaptation. We first describe a new summary statistic, Z(g), that measures the between-sample component of linkage disequilibrium (LD). We then report results of a multilocus survey of nucleotide diversity and LD between high- and low-altitude populations of deer mice, Peromyscus maniculatus. The multilocus survey included two closely linked alpha-globin genes, HBA-T1 and HBA-T2, that underlie adaptation to different elevational zones. The primary goals were to assess whether the alpha-globin genes exhibit the hallmarks of spatially varying selection that are predicted by theory (i.e., sharply defined peaks in the between-population components of nucleotide diversity and LD) and to assess whether peaks in diversity and LD may be useful for identifying specific sites that distinguish selectively maintained alleles. Consistent with theoretical expectations, HBA-T1 and HBA-T2 were characterized by highly elevated levels of diversity between populations and between allele classes. Simulation and empirical results indicate that sliding-window analyses of Z(g) between allele classes may provide an effective means of pinpointing causal substitutions.

Genome-Wide Patterns of Nucleotide Polymorphism in Domesticated Rice

Domesticated Asian rice (Oryza sativa) is one of the oldest domesticated crop species in the world, having fed more people than any other plant in human history. We report the patterns of DNA sequence variation in rice and its wild ancestor, O. rufipogon, across 111 randomly chosen gene fragments, and use these to infer the evolutionary dynamics that led to the origins of rice. There is a genome-wide excess of high-frequency derived single nucleotide polymorphisms (SNPs) in O. sativa varieties, a pattern that has not been reported for other crop species. We developed several alternative models to explain contemporary patterns of polymorphisms in rice, including a (i) selectively neutral population bottleneck model, (ii) bottleneck plus migration model, (iii) multiple selective sweeps model, and (iv) bottleneck plus selective sweeps model. We find that a simple bottleneck model, which has been the dominant demographic model for domesticated species, cannot explain the derived nucleotide polymorphism site frequency spectrum in rice. Instead, a bottleneck model that incorporates selective sweeps, or a more complex demographic model that includes subdivision and gene flow, are more plausible explanations for patterns of variation in domesticated rice varieties. If selective sweeps are indeed the explanation for the observed nucleotide data of domesticated rice, it suggests that strong selection can leave its imprint on genome-wide polymorphism patterns, contrary to expectations that selection results only in a local signature of variation.

Global phylogeography of the band-rumped storm-petrel ( Oceanodroma castro; Procellariiformes: Hydrobatidae)

Factors shaping population differentiation in low latitude seabirds are not well-understood. In this study, we examined global patterns of DNA sequence variation in the mitochondrial control region of the band-rumped storm-petrel ( Oceanodroma castro), a highly pelagic seabird distributed across the sub-tropical and tropical Atlantic and Pacific Oceans. Despite previous classification as a single, monotypic species, fixed haplotype differences occurred between Atlantic and Pacific populations, and among all Pacific populations. In addition, Cape Verde and Galapagos birds formed distinct clades, estimated to have diverged from all other populations at least 150,000 years ago. Azores hot season populations were also genetically distinct, lending support to previous phenotypic evidence that they be recognized as a separate species. Seasonal populations in Madeira probably represent separate genetic management units. The phylogeography of the band-rumped storm-petrel appears to have been shaped by both nonphysical barriers to gene flow and Pleistocene oceanographic conditions. Ancestral populations likely expanded through contiguous range expansion and infrequent long-distance colonization into their current breeding range. These findings suggest several possible revisions to the taxonomy of the band-rumped storm-petrel.

Biodiversity genomics for species at risk: patterns of DNA sequence variation within and among complete mitochondrial genomes of three species of wolffish (Anarhichas spp.)

The first marine fish species to be listed under the Canadian Species At Risk Act as Threatened with extinction are the spotted wolffish ( Anarhichas minor Olafsen, 1774) and the broadhead wolffish ( Anarhichas denticulatus Krøyer, 1844); a third species, the striped wolffish ( Anarhichas lupus L., 1758), is listed as a species of special concern. As part of the recovery plan for wolffish, we determined the complete mitochondrial DNA (mtDNA) genome sequences of all three species to identify the most variable gene regions for population analysis. Anarhichas genomes comprise either 16 519 or 16 520 base pairs (bp), among which there are 449 single nucleotide polymorphisms (SNPs). The most variable protein-coding loci are ND4, CYTB, and ND2, with 4.40, 4.22, and 4.19 SNPs / 100 bp, respectively. Comparisons of rates of synonymous and nonsynonymous nucleotide substitutions indicate no evidence of selection. The control region, characterized in many species as hypervariable, was less variable than 9 of 13 protein-coding loci (2.45 SNPs / 100 bp). Phylogenetic analysis shows that A. lupus and A. minor are more closely related to each other than either is to A. denticulatus. Amplification and sequence analysis of a contiguous block of 6392 bp that spans the ND4, ND5, ND6, and CYTB loci is an efficient strategy for evaluating patterns of intraspecific mtDNA variability.

Evolution of Amino-Acid Sequences and Codon Usage on the Drosophila miranda Neo-Sex Chromosomes

We have studied patterns of DNA sequence variation and evolution for 22 genes located on the neo-X and neo-Y chromosomes of Drosophila miranda. As found previously, nucleotide site diversity is greatly reduced on the neo-Y chromosome, with a severely distorted frequency spectrum. There is also an accelerated rate of amino-acid sequence evolution on the neo-Y chromosome. Comparisons of nonsynonymous and silent variation and divergence suggest that amino-acid sequences on the neo-X chromosome are subject to purifying selection, whereas this is much weaker on the neo-Y. The same applies to synonymous variants affecting codon usage. There is also an indication of a recent relaxation of selection on synonymous mutations for genes on other chromosomes. Genes that are weakly expressed on the neo-Y chromosome appear to have a faster rate of accumulation of both nonsynonymous and unpreferred synonymous mutations than genes with high levels of expression, although the rate of accumulation when both types of mutation are pooled is higher for the neo-Y chromosome than for the neo-X chromosome even for highly expressed genes.