Understanding invasion history: genetic structure and diversity of two globally invasive plants and implications for their management

Aim: Resolving the origin of invasive plant species is important for understanding the introduction histories of successful invaders and aiding strategies aimed at their management. This study aimed to infer the number and origin(s) of introduction for the globally invasive species, Macfadyena unguis-cati and Jatropha gossypiifolia using molecular data. Location: Native range: Neotropics; Invaded range: North America, Africa, Europe, Asia, Pacific Islands and Australia. Methods: We used chloroplast microsatellites (cpSSRs) to elucidate the origin(s) of introduced populations and calculated the genetic diversity in native and introduced regions. Results: Strong genetic structure was found within the native range of M. unguis-cati, but no genetic structuring was evident in the native range of J. gossypiifolia. Overall, 27 haplotypes were found in the native range of M. unguis-cati. Only four haplotypes were found in the introduced range, with more than 96% of introduced specimens matching a haplotype from Paraguay. In contrast, 15 haplotypes were found in the introduced range of J. gossypiifolia, with all invasive populations, except New Caledonia, comprising multiple haplotypes. Main conclusions: These data show that two invasive plant species from the same native range have had vastly different introduction histories in their non-native ranges. Invasive populations of M. unguis-cati probably came from a single or few independent introductions, whereas most invasive J. gossypiifolia populations arose from multiple introductions or alternatively from a representative sample of genetic diversity from a panmictic native range. As introduced M. unguis-cati populations are dominated by a single haplotype, locally adapted natural enemies should make the best control agents. However, invasive populations of J. gossypiifolia are genetically diverse and the selection of bio-control agents will be considerably more complex.

Temporal genetic structure patterns in tropical maize populations under reciprocal recurrent selection.

In order to investigate the effect of long term recurrent selection on the pattern of gene diversity, thirty randomly-selected individuals from the progenitors (p) and four selection cycles (C0, C3, C6 and C11) were sampled for DNA analysis from the tropical maize (Zea mays L.) breeding populations, Atherton 1 (AT1) and Atherton 2 (AT2). Fifteen polymorphic Simple Sequence Repeat markers amplified a total of 284 and 257 alleles in AT1 and AT2 populations, respectively. Reductions in the number of alleles were observed at advanced selection cycles. About 11 and 12% of the alleles in AT1 and AT2 populations respectively, were near to fixation. However, a higher number of alleles (37% in AT1 and 33% in AT2) were close to extinction. Fisher's exact test and analysis of molecular variance (AMOVA) showed significant population differentiations. Gene diversity estimates and AMOVA revealed increased genetic differentiations at the expense of loss of heterozygosity. Population differentiations were mainly due to fixation of complementary alleles at a locus in the two breeding populations. The estimates of effective population at an advanced selection cycle were close to the population size predicted by the breeding method.

Negligible evidence for regional genetic population structure for two shark species Rhizoprionodon acutus (Rüppell, 1837) and Sphyrna lewini (Griffith & Smith, 1834) with contrasting biology

Biodiversity of sharks in the tropical Indo-Pacific is high, but species-specific information to assist sustainable resource exploitation is scarce. The null hypothesis of population genetic homogeneity was tested for scalloped hammerhead shark (Sphyrna lewini, n = 237) and the milk shark (Rhizoprionodon acutus, n = 207) from northern and eastern Australia, using nuclear (S. lewini, eight microsatellite loci; R. acutus, six loci) and mitochondrial gene markers (873 base pairs of NADH dehydrogenase subunit 4). We were unable to reject genetic homogeneity for S. lewini, which was as expected based on previous studies of this species. Less expected were similar results for R. acutus, which is more benthic and less vagile than S. lewini. These features are probably driving the genetic break found between Australian and central Indonesian R. acutus (F-statistics; mtDNA, 0.751–0.903, respectively; microsatellite loci, 0.038–0.047 respectively). Our results support the spatially homogeneous monitoring and management plan for shark species in Queensland, Australia.

Migration of green turtles (Chelonia mydas) from Australasian feeding grounds inferred from genetic analyses

Coastal seagrass habitats in tropical and subtropical regions support aggregations of resident green turtles (Chelonia mydas) from several genetically distinct breeding populations. Migration of individuals to their respective dispersed breeding sites provides a complex pattern of migratory connectivity among nesting and feeding habitats of this species. An understanding of this pattern is important in regions where the persistence of populations is under threat from anthropogenic impacts. The present study uses mitochondrial DNA and mixed-stock analyses to assess the connectivity among seven feeding grounds across the north Australian coast and adjacent areas and 17 genetically distinct breeding populations from the Indo-Pacific region. It was hypothesised that large and geographically proximate breeding populations would dominate at nearby feeding grounds. As expected, each sampled feeding area appears to support multiple breeding populations, with two aggregations dominated by a local breeding population. Geographic distance between breeding and feeding habitat strongly influenced whether a breeding population contributed to a feeding ground (wi = 0.654); however, neither distance nor size of a breeding population was a good predictor of the extent of their contribution. The differential proportional contributions suggest the impact of anthropogenic mortality at feeding grounds should be assessed on a case-by-case basis.

Towards better management of Australia’s shark fishery: genetic analyses reveal unexpected ratios of cryptic blacktip species Carcharhinus tilstoni and C. limbatus

The common blacktip shark (Carcharhinus limbatus) and the Australian blacktip shark (C. tilstoni) are morphologically similar species that co-occur in subtropical and tropical Australia. In striking contrast to what has been previously reported, we demonstrate that the common blacktip shark is not rare in northern Australia but occurs in approximately equal frequencies with the Australian blacktip shark. Management of shark resources in northern Australia needs to take account of this new information. Species identification was performed using nucleotide sequences of the control, NADH dehydrogenase subunit 4 (ND4) and cytochrome oxidase I (COI) regions in the mitochondrial genome. The proportion of overall genetic variation (FST) between the two species was small (0.042, P < 0.01) based on allele frequencies at five microsatellite loci. We confirm that a third blacktip species (C. amblyrhynchoides, graceful shark) is closely related to C. tilstoni and C. limbatus and can be distinguished from them on the basis of mtDNA sequences from two gene regions. The Australian blacktip shark (C. tilstoni) was not encountered among 20 samples from central Indonesia that were later confirmed to be common blacktip and graceful sharks. Fisheries regulators urgently need new information on life history, population structure and morphological characters for species identification of blacktip shark species in Australia.

Population genetic evidence for the east–west division of the narrow-barred Spanish mackerel (Scomberomorus commerson, Perciformes: Teleostei) along Wallace’s Line

Mitochondrial DNA D-loop (control) region (426-bp) was used to infer the genetic structure of Spanish mackerel (Scomberomorus commerson) from populations in Southeast Asia (Brunei, East and West Malaysia, Philippines, Thailand, Singapore, and China) and northern Australia (including western Timor). An east–west division along Wallace’s Line was strongly supported by a significant AMOVA, with 43% of the total sequence variation partitioned among groups of populations. Phylogenetic and network analyses supported two clades: clade A and clade B. Members of clade A were found in Southeast Asia and northern Australia, but not in locations to the west (Gulf of Thailand) or north (China). Clade B was found exclusively in Southeast Asia. Genetic division along Wallace’s Line suggests that co-management of S. commerson populations for future sustainability may not be necessary between Southeast Asian nations and Australia, however all countries should share the task of management of the species in Southeast Asia equally. More detailed genetic studies of S. commerson populations in the region are warranted.

IUCN classification zones concord with, but underestimate, the population genetic structure of the zebra shark Stegostoma fasciatum in the Indo-West Pacific

The Indo-West Pacific (IWP), from South Africa in the western Indian Ocean to the western Pacific Ocean, contains some of the most biologically diverse marine habitats on earth, including the greatest biodiversity of chondrichthyan fishes. The region encompasses various densities of human habitation leading to contrasts in the levels of exploitation experienced by chondrichthyans, which are targeted for local consumption and export. The demersal chondrichthyan, the zebra shark, Stegostoma fasciatum, is endemic to the IWP and has two current regional International Union for the Conservation of Nature (IUCN) Red List classifications that reflect differing levels of exploitation: ‘Least Concern’ and ‘Vulnerable’. In this study, we employed mitochondrial ND4 sequence data and 13 microsatellite loci to investigate the population genetic structure of 180 zebra sharks from 13 locations throughout the IWP to test the concordance of IUCN zones with demographic units that have conservation value. Mitochondrial and microsatellite data sets from samples collected throughout northern Australia and Southeast Asia concord with the regional IUCN classifications. However, we found evidence of genetic subdivision within these regions, including subdivision between locations connected by habitat suitable for migration. Furthermore, parametric FST analyses and Bayesian clustering analyses indicated that the primary genetic break within the IWP is not represented by the IUCN classifications but rather is congruent with the Indonesian throughflow current. Our findings indicate that recruitment to areas of high exploitation from nearby healthy populations in zebra sharks is likely to be minimal, and that severe localized depletions are predicted to occur in zebra shark populations throughout the IWP region.

The extent of population genetic subdivision differs among four co-distributed shark species in the Indo-Australian archipelago

Background: The territorial fishing zones of Australia and Indonesia are contiguous to the north of Australia in the Timor and Arafura Seas and in the Indian Ocean to the north of Christmas Island. The area surrounding the shared boundary consists of a variety of bio-diverse marine habitats including shallow continental shelf waters, oceanic trenches and numerous offshore islands. Both countries exploit a variety of fisheries species, including whaler (Carcharhinus spp.) and hammerhead sharks (Sphyrna spp.). Despite their differences in social and financial arrangements, the two countries are motivated to develop complementary co-management practices to achieve resource sustainability. An essential starting point is knowledge of the degree of population subdivision, and hence fisheries stock status, in exploited species. Results: Populations of four commercially harvested shark species (Carcharhinus obscurus, Carcharhinus sorrah, Prionace glauca, Sphyrna lewini) were sampled from northern Australia and central Indonesia. Neutral genetic markers (mitochondrial DNA control region sequence and allelic variation at co-dominant microsatellite loci) revealed genetic subdivision between Australian and Indonesian populations of C. sorrah. Further research is needed to address the possibility of genetic subdivision among C. obscurus populations. There was no evidence of genetic subdivision for P. glauca and S. lewini populations, but the sampling represented a relatively small part of their distributional range. For these species, more detailed analyses of population genetic structure is recommended in the future. Conclusion: Cooperative management between Australia and Indonesia is the best option at present for P. glauca and S. lewini, while C. sorrah and C. obscurus should be managed independently. On-going research on these and other exploited shark and ray species is strongly recommended. Biological and ecological similarity between species may not be a predictor of population genetic structure, so species-specific studies are recommended to provide new data to assist with sustainable fisheries management.

Genome-wide association study identifies novel genetic variants contributing to variation in blood metabolite levels

Metabolites are small molecules involved in cellular metabolism, which can be detected in biological samples using metabolomic techniques. Here we present the results of genome-wide association and meta-analyses for variation in the blood serum levels of 129 metabolites as measured by the Biocrates metabolomic platform. In a discovery sample of 7,478 individuals of European descent, we find 4,068 genome- and metabolome-wide significant (Z-test, P<1.09 × 10−9) associations between single-nucleotide polymorphisms (SNPs) and metabolites, involving 59 independent SNPs and 85 metabolites. Five of the fifty-nine independent SNPs are new for serum metabolite levels, and were followed-up for replication in an independent sample (N=1,182). The novel SNPs are located in or near genes encoding metabolite transporter proteins or enzymes (SLC22A16, ARG1, AGPS and ACSL1) that have demonstrated biomedical or pharmaceutical importance. The further characterization of genetic influences on metabolic phenotypes is important for progress in biological and medical research.

Population genetic structure and genetic diversity of three critically endangered Pristis sawfishes in Australian waters.

Northern Australia is considered to be one of the last strongholds for three critically endangered sawfishes, Pristis zijsron, Pristis clavata, and Pristis microdon, making these populations of global significance. Population structure and levels of genetic diversity were assessed for each species across northern Australia using a portion of the mitochondrial control region. Statistically significant genetic structure was detected in all three species, although it was higher in P. microdon (F-ST = 0.811; N = 149) than in either P. clavata (F-ST = 0.419; N = 73) or P. zijsron (F-ST = 0.202; N = 49), possibly due to a much higher and/or localized level of female philopatry in P. microdon. The overall levels of haplotype diversity in P. zijsron (h = 0.555), P. clavata (h = 0.489), and P. microdon (h = 0.650) were moderate, although it appears to be reduced in the assemblages of P. zijsron and P. clavata in the Gulf of Carpentaria (h = 0.342 and h = 0.083, respectively). Since female migration (replenishment) between regions is unlikely, conservation plans should strive to maintain current levels of diversity and abundances in the regional assemblages of each species.

Genetic and Epigenetic Characterization of Colorectal and Endometrial Cancer

Colorectal cancer is one of the three most common cancers today, for both men and women. Approximately 90% of the cases are sporadic while the remaining 10% is hereditary. Among this 10% is hereditary nonpolyposis colorectal cancer (HNPCC), an autosomal dominant disease, accounting for up to 13% of these cases. HNPCC is associated with germline mutations in four mismatch repair (MMR) genes, MLH1, MSH2, MSH6, and PMS2, and is characterized by a familial accumulation of endometrial, gastric, urological, and ovarian tumors, in addition to colorectal cancer. An important etiological characteristic of HNPCC is the presence of microsatellite instability (MSI), caused by mutations of the MMR genes. Approximately 15% of sporadic cases share the MSI+ trait. Colon cancer is believed to be a consequence of an accumulation of mutations in tumor suppressor genes and oncogenes, eventually resulting in tumor development. This phenomena is accelerated in HNPCC due the presence of an inherited mutation in the MMR genes, accounting for one of the two hits proposed to be needed by Knudson (1971) in order for the manifestation of the MSI phenotype. MMR alterations alone, however, do not occur in the majority of sporadic colon cancers, prompting searches for other mechanisms. One such mechanism found to play a role in colon cancer development was DNA methylation, which is known to play a role in MLH1 inactivation. Our objective was clarification of mechanisms associated with tumor development in both HNPCC and sporadic colorectal cancer in relation to tumorigenic mechanisms. Of particular interest were underlying mechanisms of MSI in sporadic colorectal cancers, with attention to DNA methylation changes and their correlation to MSI. Of additional interest were the genetic and epigenetic events leading to the HNPCC tumor spectrum, chiefly colon and endometrial cancers, in regards to what extent the somatic changes in target tissue explained this phenomenon. We made a number of important findings pertaining to these questions. First, MSI tumor development differs epigenetically from stable tumor development, possibly underlying developmental pathway differences. Additionally, while epigenetic modification, principally DNA methylation, is a major mechanism in sporadic MSI colorectal cancer MLH1 inactivation it does not play a significant role in HNPCC tumors with germline MLH1 mutations. This is possibly an explanation for tumorigenic pathways and clinicopathological characteristic differences between sporadic and hereditary MSI colorectal cancers. Finally, despite indistinguishable genetic predisposition for endometrial and colorectal cancers, instability profiles highlighting organ-specific differences, may be important HNPCC tumor spectrum determinants.

p53 and DNA damage checkpoint responses in the human prostate

Prostate cancer is the most common noncutaneous malignancy and the second leading cause of cancer mortality in men. In 2004, 5237 new cases were diagnosed and altogether 25 664 men suffered from prostate cancer in Finland (Suomen Syöpärekisteri). Although extensively investigated, we still have a very rudimentary understanding of the molecular mechanisms leading to the frequent transformation of the prostate epithelium. Prostate cancer is characterized by several unique features including the multifocal origin of tumors and extreme resistance to chemotherapy, and new treatment options are therefore urgently needed. The integrity of genomic DNA is constantly challenged by genotoxic insults. Cellular responses to DNA damage involve elegant checkpoint cascades enforcing cell cycle arrest, thus facilitating damage repair, apoptosis or cellular senescence. Cellular DNA damage triggers the activation of tumor suppressor protein p53 and Wee1 kinase which act as executors of the cellular checkpoint responses. These are essential for genomic integrity, and are activated in early stages of tumorigenesis in order to function as barriers against tumor formation. Our work establishes that the primary human prostatic epithelial cells and prostatic epithelium have unexpectedly indulgent checkpoint surveillance. This is evidenced by the absence of inhibitory Tyr15 phosphorylation on Cdk2, lack of p53 response, radioresistant DNA synthesis, lack of G1/S and G2/M phase arrest, and presence of persistent gammaH2AX damage foci. We ascribe the absence of inhibitory Tyr15 phosphorylation to low levels of Wee1A, a tyrosine kinase and negative regulator of cell cycle progression. Ectopic Wee1A kinase restored Cdk2-Tyr15 phosphorylation and efficiently rescued the ionizing radiation-induced checkpoints in the human prostatic epithelial cells. As variability in the DNA damage responses has been shown to underlie susceptibility to cancer, our results imply that a suboptimal checkpoint arrest may greatly increase the accumulation of genetic lesions in the prostate epithelia. We also show that small molecules can restore p53 function in prostatic epithelial cells and may serve as a paradigm for the development of future therapeutic agents for the treatment of prostate cancer We hypothesize that the prostate has evolved to activate the damage surveillance pathways and molecules involved in these pathways only to certain stresses in extreme circumstances. In doing so, this organ inadvertently made itself vulnerable to genotoxic stress, which may have implications in malignant transformation. Recognition of the limited activity of p53 and Wee1 in the prostate could drive mechanism-based discovery of preventative and therapeutic agents.

Coordinator's report: descriptions of barley genetic stocks for 2010.

In this volume, 64 new and revised barley genetic stock (BGS) descriptions for 2010 are presented. The current lists of new and revised BGS descriptions are presented by BGS number order and by locus symbol in alphabetical order. Information on the description location, recommended locus name, chromosomal location, previous gene symbols, and the primary genetic stock (GSHO number and/or NGB number) are included in these lists.

Genetic analysis for a shared biological basis between migraine and coronary artery disease

Objective: To apply genetic analysis of genome-wide association data to study the extent and nature of a shared biological basis between migraine and coronary artery disease (CAD). Methods: Four separate methods for cross-phenotype genetic analysis were applied on data from 2 large-scale genome-wide association studies of migraine (19,981 cases, 56,667 controls) and CAD (21,076 cases, 63,014 controls). The first 2 methods quantified the extent of overlapping risk variants and assessed the load of CAD risk loci in migraineurs. Genomic regions of shared risk were then identified by analysis of covariance patterns between the 2 phenotypes and by querying known genome-wide significant loci. Results: We found a significant overlap of genetic risk loci for migraine and CAD. When stratified by migraine subtype, this was limited to migraine without aura, and the overlap was protective in that patients with migraine had a lower load of CAD risk alleles than controls. Genes indicated by 16 shared risk loci point to mechanisms with potential roles in migraine pathogenesis and CAD, including endothelial dysfunction (PHACTR1) and insulin homeostasis (GIP). Conclusions: The results suggest that shared biological processes contribute to risk of migraine and CAD, but surprisingly this commonality is restricted to migraine without aura and the impact is in opposite directions. Understanding the mechanisms underlying these processes and their opposite relationship to migraine and CAD may improve our understanding of both disorders.

New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10−8). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.