Quantum speciation in Aegilops: molecular cytogenetic evidence from rDNA cluster variability in natural populations

Data are presented on quantum speciation in the Sitopsis section of the genus Aegilops (Poaceae, Monocotyledones). Two small, peripheral, isolated, wild populations of annual cross-pollinated Ae. speltoides and annual self-pollinated Ae. sharonensis are located 30 m apart on different soil types. Despite the close proximity of the two species and their close relatedness, no mixed groups are known. Comparative molecular cytogenetic analysis based on the intrapopulation variability of rRNA-encoding DNA (rDNA) chromosomal patterns of individual Ae. speltoides geno-types revealed an ongoing dynamic process of permanent chromosomal rearrangements. Chromosomal mutations can arise de novo and can be eliminated. Analysis of the progeny of the investigated genotypes testifies that inheritance of de novo rDNA sites happens frequently. Heterologous recombination and/or transposable elements-mediated rDNA transfer seem to be the mechanisms for observed chromosomal repatterning. Consequently, several modified genomic forms, intermediate between Ae. speltoides and Ae. sharonensis, permanently arise in the studied wild population of Ae. speltoides, which make it possible to recognize Ae. sharonensis as a derivative species of Ae. speltoides, as well as to propose rapidness and canalization of quantum speciation in Sitopsis species.     

Allopolyploid speciation in Persicaria (Polygonaceae): insights from a low-copy nuclear region

Using a low-copy nuclear gene region (LEAFY second intron) we show multiple instances of allopolyploid speciation in Persicaria (Polygonaceae), which includes many important weeds. Fifteen species seem to be allopolyploids, which is higher than the number found in previous comparisons of chloroplast DNA and nuclear ribosomal internal transcribed spacer (nrITS) phylogenies. This underestimation of the extent of allopolyploidy is due in at least three cases to homogenization of nrITS toward the maternal lineage. One of the diploid species, P. lapathifolia, has been involved in at least six cases of allopolyploid speciation. Of the diploids, this species is the most widespread geographically and ecologically and also bears more numerous and conspicuous flowers, illustrating ecologic factors that may influence hybridization frequency. With a few exceptions, especially the narrowly endemic hexaploid, P. puritanorum, the allopolyploid species also are widespread, plastic, ecological generalists. Hybridization events fostered by human introductions may be fueling the production of new species that have the potential to become aggressive weeds.     

Sunflower domestication alleles support single domestication center in eastern North America

Phylogenetic analyses of genes with demonstrated involvement in evolutionary transitions can be an important means of resolving conflicting hypotheses about evolutionary history or process. In sunflower, two genes have previously been shown to have experienced selective sweeps during its early domestication. In the present study, we identified a third candidate early domestication gene and conducted haplotype analyses of all three genes to address a recent, controversial hypothesis about the origin of cultivated sunflower. Although the scientific consensus had long been that sunflower was domesticated once in eastern North America, the discovery of pre-Columbian sunflower remains at archaeological sites in Mexico led to the proposal of a second domestication center in southern Mexico. Previous molecular studies with neutral markers were consistent with the former hypothesis. However, only two indigenous Mexican cultivars were included in these studies, and their provenance and genetic purity have been questioned. Therefore, we sequenced regions of the three candidate domestication genes containing SNPs diagnostic for domestication from large, newly collected samples of Mexican sunflower landraces and Mexican wild populations from a broad geographic range. The new germplasm also was genotyped for 12 microsatellite loci. Our evidence from multiple evolutionarily important loci and from neutral markers supports a single domestication event for extant cultivated sunflower in eastern North America.     

INAUGURAL ARTICLE by a Recently Elected Academy Member:Causes of natural variation in fitness: Evidence from studies of Drosophila populations

DNA sequencing has revealed high levels of variability within most species. Statistical methods based on population genetics theory have been applied to the resulting data and suggest that most mutations affecting functionally important sequences are deleterious but subject to very weak selection. Quantitative genetic studies have provided information on the extent of genetic variation within populations in traits related to fitness and the rate at which variability in these traits arises by mutation. This paper attempts to combine the available information from applications of the two approaches to populations of the fruitfly Drosophila in order to estimate some important parameters of genetic variation, using a simple population genetics model of mutational effects on fitness components. Analyses based on this model suggest the existence of a class of mutations with much larger fitness effects than those inferred from sequence variability and that contribute most of the standing variation in fitness within a population caused by the input of mildly deleterious mutations. However, deleterious mutations explain only part of this standing variation, and other processes such as balancing selection appear to make a large contribution to genetic variation in fitness components in Drosophila.Advances in DNA sequencing methods have enabled geneticists to measure the amount of genetic variability in natural populations at the most basic level: the frequencies of variants in nucleotide sequences. This achievement has ended one component of a debate on the extent and causes of genetic variability that was initiated in the 1950s by Hermann Muller and Theodosius Dobzhansky (1, 2); we now know that DNA sequences are highly variable within the populations of most species (3). It has, however, been much harder to provide a definitive answer to the other component of this debate, which concerns the nature and intensity of the evolutionary forces that influence the frequencies of genetic variants within populations (1, 2, 4, 5). Are these variants mostly selectively neutral (6), with the fates of new mutations determined by random fluctuations in their frequencies (genetic drift)? Is selection on variants that affect fitness mostly purifying, so that mutations with harmful effects are rapidly removed from the population (1)? Or do many loci have variants maintained by balancing selection (2)? What fraction of newly arisen variants cause higher fitness and are in the process of spreading through the population and replacing their alternatives? How strong is the selection acting on nonneutral variants, and how much variation in fitness among individuals within populations is contributed by such variants? Does the existence of wide variation in fitness among individuals imply a genetic load that threatens the survival of the species (1)?These questions are very broad, and this paper deals only with one aspect of them. It focuses on the question of how recent inferences concerning the strength of purifying selection, derived from genome-wide surveys of DNA sequence variability, can be connected with the results of statistical studies of genetic variation in components of Darwinian fitness such as viability and fertility. I will refer to these two approaches as population genomics and quantitative genetics, respectively. The first approach sheds light on the general nature of the fitness effects of the DNA sequence variants found in natural populations, but says little about how these fitness effects are caused. The second tells us how much genetic variability exists for fitness traits, the rate at which it arise by mutation and something about the type of selection involved, but is silent about the nature of the underlying sequence variants.Surprisingly little attention has been paid to integrating these two lines of inquiry, except for ref. 7. I largely confine myself to results from studies of the fruitfly Drosophila, because this has been the most useful model organism for investigating these problems, especially by quantitative genetics methods. Current information derived from population genomics studies will first be reviewed, followed by an analysis of the results of quantitative genetics experiments on both mutational and standing variation. I show that the quantitative genetics results can only be explained if there is a significant input of new mutations with much larger effects on fitness than those inferred from population genomics. There also appears to be too much genetic variation in fitness components in natural populations to be explained purely by mutation selection balance, so that additional processes such as balancing selection must make an important contribution.     

Widespread genomic divergence during sympatric speciation

Speciation with gene flow is expected to generate a heterogeneous pattern of genomic differentiation. The few genes under or physically linked to loci experiencing strong disruptive selection can diverge, whereas gene flow will homogenize the remainder of the genome, resulting in isolated “genomic islands of speciation.” We conducted an experimental test of this hypothesis in Rhagoletis pomonella, a model for sympatric ecological speciation. Contrary to expectations, we found widespread divergence throughout the Rhagoletis genome, with the majority of loci displaying host differences, latitudinal clines, associations with adult eclosion time, and within-generation responses to selection in a manipulative overwintering experiment. The latter two results, coupled with linkage disequilibrium analyses, provide experimental evidence that divergence was driven by selection on numerous independent genomic regions rather than by genome-wide genetic drift. “Continents” of multiple differentiated loci, rather than isolated islands of divergence, may characterize even the early stages of speciation. Our results also illustrate how these continents can exhibit variable topography, depending on selection strength, availability of preexisting genetic variation, linkage relationships, and genomic features that reduce recombination. For example, the divergence observed throughout the Rhagoletis genome was clearly accentuated in some regions, such as those harboring chromosomal inversions. These results highlight how the individual genes driving speciation can be embedded within an actively diverging genome.     

Global divergence of the human follicle mite Demodex folliculorum: Persistent associations between host ancestry and mite lineages

Microscopic mites of the genus Demodex live within the hair follicles of mammals and are ubiquitous symbionts of humans, but little molecular work has been done to understand their genetic diversity or transmission. Here we sampled mite DNA from 70 human hosts of diverse geographic ancestries and analyzed 241 sequences from the mitochondrial genome of the species Demodex folliculorum. Phylogenetic analyses recovered multiple deep lineages including a globally distributed lineage common among hosts of European ancestry and three lineages that primarily include hosts of Asian, African, and Latin American ancestry. To a great extent, the ancestral geography of hosts predicted the lineages of mites found on them; 27% of the total molecular variance segregated according to the regional ancestries of hosts. We found that D. folliculorum populations are stable on an individual over the course of years and that some Asian and African American hosts maintain specific mite lineages over the course of years or generations outside their geographic region of birth or ancestry. D. folliculorum haplotypes were much more likely to be shared within families and between spouses than between unrelated individuals, indicating that transmission requires close contact. Dating analyses indicated that D. folliculorum origins may predate modern humans. Overall, D. folliculorum evolution reflects ancient human population divergences, is consistent with an out-of-Africa dispersal hypothesis, and presents an excellent model system for further understanding the history of human movement.Human evolution did not take place in isolation but instead occurred alongside that of many closely associated species. Phylogeographic studies of human-associated species—such as lice and rodents, as well as certain bacteria and viruses—have suggested, eliminated, and confirmed hypotheses about human history (1–10). For example, these studies have provided details about the timing and nature of the original human migration out of Africa, the spread of humans within and among continents, and the domestication of large vertebrates.Mites of the genus Demodex live in the hair follicles and sebaceous glands of humans and provide a promising system with which to explore further the details of human evolution. The association between Demodex and Homo sapiens is likely to be an ancient one: The broad distribution of these mites across mammal species (11), coupled with the ancient date of divergence estimated between the two species known to be found on humans (12), suggests that Demodex originated and diversified with early mammals. Furthermore, Demodex seem likely to have been carried along whenever their hosts migrated, because they are ubiquitous inhabitants of human skin (13, 14). Finally, in comparison with the other human associates that have been studied to date, Demodex mites are more tightly associated with human bodies than are lice, while their generation times are slower than those of bacteria and viruses but are faster than those of rodents, making them a complementary system with which to understand the evolution of both humans and human associates.Two species of Demodex are known to inhabit the skin of humans. Histological studies suggest that each occupies a different niche: Demodex folliculorum resides in the hair follicle and is often found near the skin surface, whereas Demodex brevis is generally found deep in the sebaceous glands (15). As a result, the frequency of D. folliculorum movement from one host to another may be greater than that of D. brevis. A recent phylogenetic analysis of Demodex, including the two human associates, shows geographically structured genetic variation in D. brevis in which individuals of European descent and those of temperate Asian (Chinese) descent exhibit up to 6% divergence in nuclear ribosomal 18S sequence (14). In contrast, studies based on 18S rDNA and 16S mtDNA suggest that D. folliculorum exhibits no clear geographic structure among hosts from China, Spain, Brazil, and the United States (14, 16, 17). However, without additional sampling it is impossible to know whether the absence of apparent geographic structure in D. folliculorum truly reflects high rates of global gene flow or instead is an artifact of limited global sampling and the particular genetic loci studied.Key to understanding the global phylogeography of these mites is an understanding of how they move among hosts. The transfer of mites from mother to progeny and between mating partners has been demonstrated in nonhuman mammals (18–21). However, the movement of Demodex among human hosts has not been characterized. If human mites are transferred between hosts at high rates, the resulting high rates of migration could account for the limited geographic structure observed in D. folliculorum to date.Here we used a 930-bp fragment of the mitochondrial genome to evaluate the genetic diversity and phylogeography of D. folliculorum among 70 human hosts of diverse geographic origins and ancestries. Our samples included people of European, Asian, African, and Latin American descent, the majority of whom currently live in the United States, providing the most broadly sampled evolutionary tree to date for any Demodex species.Additionally, we investigated Demodex transmission among humans in two ways. First, we sampled multiple mites from a single host individual over the course of 3 y to characterize the diversity and stability of the mite population. Second, we examined the relationships among mites on three sets of parents and their adult progeny; because of the close association among family members, we hypothesized that mite lineages are more likely to be shared within families than between unrelated hosts.The study of Demodex mites speaks to the story of human evolution as well as the coevolution between symbiont and host. Moreover, understanding these mites and their microbes will have applied value, because they have been linked to skin disorders such as rosacea and blepharitis (22, 23). Whatever the influence of mites on these disorders may be, it may depend on the mite lineages inhabiting a particular host. Ultimately, elucidating the evolution and transmission of Demodex mites not only will be a useful step toward understanding the evolutionary history of humans but also will be critical to contextualizing their role in human health.     

Genomic linkage of male song and female acoustic preference QTL underlying a rapid species radiation

The genetic coupling hypothesis of signal-preference evolution, whereby the same genes control male signal and female preference for that signal, was first inspired by the evolution of cricket acoustic communication nearly 50 years ago. To examine this hypothesis, we compared the genomic location of quantitative trait loci (QTL) underlying male song and female acoustic preference variation in the Hawaiian cricket genus Laupala. We document a QTL underlying female acoustic preference variation between 2 closely related species (Laupala kohalensis and Laupala paranigra). This preference QTL colocalizes with a song QTL identified previously, providing compelling evidence for a genomic linkage of the genes underlying these traits. We show that both song and preference QTL make small to moderate contributions to the behavioral difference between species, suggesting that divergence in mating behavior among Laupala species is due to the fixation of many genes of minor effect. The diversity of acoustic signaling systems in crickets exemplifies the evolution of elaborate male displays by sexual selection through female choice. Our data reveal genetic conditions that would enable functional coordination between song and acoustic preference divergence during speciation, resulting in a behaviorally coupled mode of signal-preference evolution. Interestingly, Laupala exhibits one of the fastest rates of speciation in animals, concomitant with equally rapid evolution in sexual signaling behaviors. Genomic linkage may facilitate rapid speciation by contributing to genetic correlations between sexual signaling behaviors that eventually cause sexual isolation between diverging populations.     

Selective loss of polymorphic mating types is associated with rapid phenotypic evolution during morphic speciation

Polymorphism may play an important role in speciation because new species could originate from the distinctive morphs observed in polymorphic populations. However, much remains to be understood about the process by which morphs found new species. To detail the steps of this mode of speciation, we studied the geographic variation and evolutionary history of a throat color polymorphism that distinguishes the “rock-paper-scissors” mating strategies of the side-blotched lizard, Uta stansburiana. We found that the polymorphism is geographically widespread and has been maintained for millions of years. However, there are many populations with reduced numbers of throat color morphs. Phylogenetic reconstruction showed that the polymorphism is ancestral, but it has been independently lost eight times, often giving rise to morphologically distinct subspecies/species. Changes to the polymorphism likely involved selection because the allele for one particular male strategy, the “sneaker” morph, has been lost in all cases. Polymorphism loss was associated with accelerated evolution of male size, female size, and sexual dimorphism, which suggests that polymorphism loss can promote rapid divergence among populations and aid species formation.     

Natal dispersal driven by environmental conditions interacting across the annual cycle of a migratory songbird

Natal dispersal, the process through which immature individuals permanently depart their natal area in search of new sites, is integral to the ecology and evolution of animals. Insights about the underlying causes of natal dispersal arise mainly from research on species whose short dispersal distances or restricted distributions make them relatively easy to track. However, for small migratory animals, the causes of natal dispersal remain poorly understood because individuals are nearly impossible to track by using conventional mark-recapture approaches. Using stable-hydrogen isotope ratios in feathers of American redstarts (Setophaga ruticilla) captured as immature birds and again as adults, we show that habitat use during the first tropical nonbreeding season appears to interact with latitudinal gradients in spring phenology on the temperate breeding grounds to influence the distance traveled on the initial spring migration and the direction of natal dispersal. In contrast, adult redstarts showed considerable site fidelity between breeding seasons, indicating that environmental conditions did not affect dispersal patterns after the first breeding attempt. Our findings suggest that habitat occupancy during the first nonbreeding season helps determine the latitude at which this species of Neotropical-Nearctic migratory bird breeds throughout its life and emphasize the need to understand how events throughout the annual cycle interact to shape fundamental biological processes.     

Association of IL-17 polymorphisms with gastric cancer risk in Asian populations

AIM: To investigate associations between the IL-17 rs2275913 GA and rs763780 TC polymorphisms and susceptibility to gastric cancer in Asian populations. METHODS: We reviewed studies published up to 2014 on IL-17 polymorphisms with gastric cancer susceptibility systematically. Relevant articles were identified in the MEDLINE, Science Citation Index, Cochrane Library, Pub Med, EMBASE, CINAHL and Current Contents Index databases. We used version 12.0 STATA statistical software to evaluate the statistical data. Two reviewers abstracted the data independently. Odds ratios(ORs) and 95% confidence intervals(95%CIs) were calculated. RESULTS: Seven independent, case-control studies were chosen for the meta-analysis, which included 3210 gastric cancer patients and 3889 healthy controls. The overall estimation showed a positive association between the IL-17 rs2275913 GA polymorphism and the occurrence of gastric cancer for five genetic models(all P 0.05) and similar results were observed for the IL-17 rs763780 TC variation with four genetic models(all P 0.05), but not for the dominant model(P 0.05). Subgroup analysis by country revealed that the rs2275913 GA and rs763780 TC polymorphisms may be the main risk factor for gastric cancer in Chinese and Japanese populations. CONCLUSION: The IL-17 gene may be significantly correlated with gastric cancer risk in Asian populations, especially those carrying the rs2275913 GA and rs763780 TC polymorphisms.     

INAUGURAL ARTICLE by a Recently Elected Academy Member:Haplotype structure strongly affects recombination in a maize genetic interval polymorphic for Helitron and retrotransposon insertions

We have asked here how the remarkable variation in maize haplotype structure affects recombination. We compared recombination across a genetic interval of 9S in 2 highly dissimilar heterozygotes that shared 1 parent. The genetic interval in the common haplotype is ≈100 kb long and contains 6 genes interspersed with gene-fragment-bearing Helitrons and retrotransposons that, together, comprise 70% of its length. In one heterozygote, most intergenic insertions are homozygous, although polymorphic, enabling us to determine whether any recombination junctions fall within them. In the other, most intergenic insertions are hemizygous and, thus, incapable of homologous recombination. Our analysis of the frequency and distribution of recombination in the interval revealed that: (i) Most junctions were circumscribed to the gene space, where they showed a highly nonuniform distribution. In both heterozygotes, more than half of the junctions fell in the stc1 gene, making it a clear recombination hotspot in the region. However, the genetic size of stc1 was 2-fold lower when flanked by a hemizygous 25-kb retrotransposon cluster. (ii) No junctions fell in the hypro1 gene in either heterozygote, making it a genic recombination coldspot. (iii) No recombination occurred within the gene fragments borne on Helitrons nor within retrotransposons, so neither insertion class contributes to the interval''s genetic length. (iv) Unexpectedly, several junctions fell in an intergenic region not shared by all 3 haplotypes. (v) In general, the ability of a sequence to recombine correlated inversely with its methylation status. Our results show that haplotypic structural variability strongly affects the frequency and distribution of recombination events in maize.     

Genetic structure and isolation by distance in a landrace of Thai rice

Rice is among the 3 most important crops worldwide. While much of the world''s rice harvest is based on modern high-yield varieties, traditional varieties of rice grown by indigenous groups have great importance as a resource for future crop improvement. These local landraces represent an intermediate stage of domestication between a wild ancestor and modern varieties and they serve as reservoirs of genetic variation. Such genetic variation is influenced both by natural processes such as selection and drift, and by the agriculture practices of local farmers. How these processes interact to shape and change the population genetics of landrace rice is unknown. Here, we determine the population genetic structure of a single variety of landrace rice, Bue Chomee, cultivated by Karen people of Thailand. Microsatellite markers reveal high level of genetic variation despite predominant inbreeding in the crop. Bue Chomee rice shows slight but significant genetic differentiation among Karen villages. Moreover, genetically determined traits such as flowering time can vary significantly among villages. An unanticipated result was the overall pattern of genetic differentiation across villages which conforms to an isolation by distance model of differentiation. Isolation by distance is observed in natural plant species where the likelihood of gene flow is inversely related to distance. In Karen rice, gene flow is the result of farmers'' seed sharing networks. Taken together, these data suggest that landrace rice is a dynamic genetic system that responds to evolutionary forces, both natural and those imposed by humans.     

Self-generated diversity produces "insurance effects" in biofilm communities

Diversity generally protects communities from unstable environmental conditions. This principle, known as the "insurance hypothesis," has been tested in many different ecosystems. Here we show that the opportunistic pathogen Pseudomonas aeruginosa undergoes extensive genetic diversification during short-term growth in biofilm communities. The induced genetic changes are produced by a recA-dependent mechanism and affect multiple traits, including the behavior of the bacteria in biofilms. Some biofilm-derived variants exhibit an increased ability to disseminate, whereas others manifest accelerated biofilm formation. Furthermore, the presence of these functionally diverse bacteria increases the ability of biofilms to resist an environmental stress. These findings suggest that self-generated diversity in biofilms provides a form of biological insurance that can safeguard the community in the face of adverse conditions.     

INAUGURAL ARTICLE by a Recently Elected Academy Member:Geographic patterns of Plasmodium falciparum drug resistance distinguished by differential responses to amodiaquine and chloroquine

Chloroquine (CQ) resistance (CQR) in Plasmodium falciparum originated from at least six foci in South America, Asia, and Oceania. Malaria parasites from these locations exhibit contrasting resistance phenotypes that are distinguished by point mutations and microsatellite polymorphisms in and near the CQR transporter gene, pfcrt, and the multidrug resistance transporter gene, pfmdr1. Amodiaquine (AQ), a 4-aminoquinoline related to CQ, is recommended and often used successfully against CQ-resistant P. falciparum in Africa, but it is largely ineffective across large regions of South America. The relationship of different pfcrt and pfmdr1 combinations to these drug-resistant phenotypes has been unclear. In two P. falciparum genetic crosses, particular pfcrt and pfmdr1 alleles from South America interact to yield greater levels of resistance to monodesethylamodiaquine (MDAQ; the active metabolite of AQ) than to CQ, whereas a pfcrt allele from Southeast Asia and Africa is linked to greater CQ than MDAQ resistance with all partner pfmdr1 alleles. These results, together with (i) available haplotype data from other parasites; (ii) evidence for an emerging focus of AQ resistance in Tanzania; and (iii) the persistence of 4-aminoquinoline-resistant parasites in South America, where CQ and AQ use is largely discontinued, suggest that different histories of drug use on the two continents have driven the selection of distinct suites of pfcrt and pfmdr1 mutations. Increasing use of AQ in Africa poses the threat of a selective sweep of highly AQ-resistant, CQ-resistant parasites with pfcrt and pfmdr1 mutations that are as advantaged and persistent as in South America.     

Circuit theory predicts gene flow in plant and animal populations

Maintaining connectivity for broad-scale ecological processes like dispersal and gene flow is essential for conserving endangered species in fragmented landscapes. However, determining which habitats should be set aside to promote connectivity has been difficult because existing models cannot incorporate effects of multiple pathways linking populations. Here, we test an ecological connectivity model that overcomes this obstacle by borrowing from electrical circuit theory. The model vastly improves gene flow predictions because it simultaneously integrates all possible pathways connecting populations. When applied to data from threatened mammal and tree species, the model consistently outperformed conventional gene flow models, revealing that barriers were less important in structuring populations than previously thought. Circuit theory now provides the best-justified method to bridge landscape and genetic data, and holds much promise in ecology, evolution, and conservation planning.     

RASGRF2 regulates alcohol-induced reinforcement by influencing mesolimbic dopamine neuron activity and dopamine release

The firing of mesolimbic dopamine neurons is important for drug-induced reinforcement, although underlying genetic factors remain poorly understood. In a recent genome-wide association metaanalysis of alcohol intake, we identified a suggestive association of SNP rs26907 in the ras-specific guanine-nucleotide releasing factor 2 (RASGRF2) gene, encoding a protein that mediates Ca²⁺-dependent activation of the ERK pathway. We performed functional characterization of this gene in relation to alcohol-related phenotypes and mesolimbic dopamine function in both mice and adolescent humans. Ethanol intake and preference were decreased in Rasgrf2^−/− mice relative to WT controls. Accordingly, ethanol-induced dopamine release in the ventral striatum was blunted in Rasgrf2^−/− mice. Recording of dopamine neurons in the ventral tegmental area revealed reduced excitability in the absence of Ras-GRF2, likely because of lack of inhibition of the I_A potassium current by ERK. This deficit provided an explanation for the altered dopamine release, presumably linked to impaired activation of dopamine neurons firing. Functional neuroimaging analysis of a monetary incentive–delay task in 663 adolescent boys revealed significant association of ventral striatal activity during reward anticipation with a RASGRF2 haplotype containing rs26907, the SNP associated with alcohol intake in our previous metaanalysis. This finding suggests a link between the RASGRF2 haplotype and reward sensitivity, a known risk factor for alcohol and drug addiction. Indeed, follow-up of these same boys at age 16 y revealed an association between this haplotype and number of drinking episodes. Together, these combined animal and human data indicate a role for RASGRF2 in the regulation of mesolimbic dopamine neuron activity, reward response, and alcohol use and abuse.     

Genome-wide association mapping of leaf metabolic profiles for dissecting complex traits in maize

The diversity of metabolites found in plants is by far greater than in most other organisms. Metabolic profiling techniques, which measure many of these compounds simultaneously, enabled investigating the regulation of metabolic networks and proved to be useful for predicting important agronomic traits. However, little is known about the genetic basis of metabolites in crops such as maize. Here, a set of 289 diverse maize inbred lines was genotyped with 56,110 SNPs and assayed for 118 biochemical compounds in the leaves of young plants, as well as for agronomic traits of mature plants in field trials. Metabolite concentrations had on average a repeatability of 0.73 and showed a correlation pattern that largely reflected their functional grouping. Genome-wide association mapping with correction for population structure and cryptic relatedness identified for 26 distinct metabolites strong associations with SNPs, explaining up to 32.0% of the observed genetic variance. On nine chromosomes, we detected 15 distinct SNP-metabolite associations, each of which explained more then 15% of the genetic variance. For lignin precursors, including p-coumaric acid and caffeic acid, we found strong associations (P values to ) with a region on chromosome 9 harboring cinnamoyl-CoA reductase, a key enzyme in monolignol synthesis and a target for improving the quality of lignocellulosic biomass by genetic engineering approaches. Moreover, lignin precursors correlated significantly with lignin content, plant height, and dry matter yield, suggesting that metabolites represent promising connecting links for narrowing the genotype-phenotype gap of complex agronomic traits.     

Cross-species genetic exchange between visceral and cutaneous strains of Leishmania in the sand fly vector

Genetic exchange between Leishmania major strains during their development in the sand fly vector has been experimentally shown. To investigate the possibility of genetic exchange between different Leishmania species, a cutaneous strain of L. major and a visceral strain of Leishmania infantum, each bearing a different drug-resistant marker, were used to coinfect Lutzomyia longipalpis sand flies. Eleven double–drug-resistant progeny clones, each the product of an independent mating event, were generated and submitted to genotype and phenotype analyses. The analysis of multiple allelic markers across the genome suggested that each progeny clone inherited at least one full set of chromosomes from each parent, with loss of heterozygosity at some loci, and uniparental retention of maxicircle kinetoplast DNA. Hybrids with DNA contents of approximately 2n, 3n, and 4n were observed. In vivo studies revealed clear differences in the ability of the hybrids to produce pathology in the skin or to disseminate to and grow in the viscera, suggesting polymorphisms and differential inheritance of the gene(s) controlling these traits. The studies, to our knowledge, represent the first experimental confirmation of cross-species mating in Leishmania, opening the way toward genetic linkage analysis of important traits and providing strong evidence that genetic exchange is responsible for the generation of the mixed-species genotypes observed in natural populations.Kinetoplastid protozoan parasites of the genus Leishmania are transmitted by a sand fly bite into the skin of the mammalian host. More than 20 different species of Leishmania are known to produce disease in humans, ranging from localized, self-limiting cutaneous lesions that develop at the site of inoculation to visceralizing infections that are fatal in the absence of treatment (1). These diverse clinical outcomes have generally clear parasite species and strain associations, although the ability of visceral strains to occasionally produce cutaneous disease, and vice versa, is also well described. The specific contribution of parasite genotype to disease outcome remains largely unknown. Studies by Zhang et al. demonstrated that the introduction of Leishmania donovani-specific genes into Leishmania major increased their ability to grow in the viscera of BALB/c mice, but in no case reached the level of infection produced by the visceral strains (2, 3), suggesting that these tissue tropisms are under multigenic control.The Leishmania genome is organized in 36 chromosomes for the Old World species, such as L. major, L. donovani, and Leishmania infantum, and in 35 and 34 for the New World species Leishmania braziliensis and Leishmania mexicana, respectively (4, 5). Although approximately a diploid organism, aneuploidy, including mosaic aneuploidy, is now known to be widespread (6–10); we refer to the nearly diploid state as “2n” here. A series of population genetic studies have suggested that clonal lineages have experienced at least occasional bouts of genetic exchange both within and between species (11–16), and the frequency of these recombination events underlies the continuing clonality vs. sexuality debate (17).By using drug-resistance markers, the first direct demonstration of genetic exchange between different L. major strains was reported (18) and possibly between L. donovani lines using fluorescent markers (19). In each case, the hybrids were generated between the extracellular promastigote stages in the sand fly vector. These and more recent studies (20, 21) critically inform the population genetics data by formally demonstrating that Leishmania are capable of intraspecies and even intraclonal mating. The present studies were designed to provide, to our knowledge, the first experimental demonstration of cross-species mating and to explore the heritability of the genes controlling tissue-specific tropisms. By using L. major and L. infantum parental lines bearing independent drug-resistance markers and that reproduce in mice their respective human cutaneous and visceral tropisms, hybrid progeny were recovered from coinfected Lutzomyia longipalpis sand flies. Detailed genotyping and phenotyping of 11 progeny clones are described.