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While many genetic diseases have effective treatments, they frequently progress rapidly to severe morbidity or mortality if those treatments are not implemented immediately. Since front-line physicians frequently lack familiarity with these diseases, timely molecular diagnosis may not improve outcomes. Herein we describe Genome-to-Treatment, an automated, virtual system for genetic disease diagnosis and acute management guidance. Diagnosis is achieved in 13.5 h by expedited whole genome sequencing, with superior analytic performance for structural and copy number variants. An expert panel adjudicated the indications, contraindications, efficacy, and evidence-of-efficacy of 9911 drug, device, dietary, and surgical interventions for 563 severe, childhood, genetic diseases. The 421 (75%) diseases and 1527 (15%) effective interventions retained are integrated with 13 genetic disease information resources and appended to diagnostic reports (https://gtrx.radygenomiclab.com). This system provided correct diagnoses in four retrospectively and two prospectively tested infants. The Genome-to-Treatment system facilitates optimal outcomes in children with rapidly progressive genetic diseases.

The Nusa Tenggara island chain consists of an archipelago that runs roughly east-west in eastern Indonesia. As part of Wallacea, it has never been connected to any continental landmass, and has been subject to a variety of biological invasions that have populated the islands. Here, we examine the craniometric and molecular genetic records of several species of Rattus sensu lato in the island chain. We use the predictions of expanding population edge phenotypic selection in an effort to understand the movement of Rattus rattus and Rattus exulans through the archipelago. We also examine the mitochondrial haplotype networks of R. argentiventer, R. exulans, and the R. rattus Complex (RrC) and microsatellite allele frequency clustering patterns for the RrC, to examine relationships within and between Nusa Tenggara populations, and those of Asia and the Pacific where relevant for each taxon. In the RrC LIV and RrC LII haplotype networks, 20 haplotypes with seven from Nusa Tenggara were observed for RrC LIV, and 100 haplotypes with seven from Nusa Tenggara observed for RrC LII. The top performing RrC craniometric model had a negative association between size and distance from the easternmost point of the samples from Nusa Tenggara, consistent with increasing size moving west to east. The cytochrome b network for the R. exulans sequences comprised 14 haplotypes, with three observed from mainland Southeast Asia, one shared with Nusa Tenggara and regions further east, and another haplotype observed in Nusa Tenggara and in the Pacific. The R. exulans craniometric model selection produced four equally well performing models, with no migration scenario preferred. Finally, the haplotype network of R. argentiventer comprised 10 haplotypes, with six observed in Nusa Tenggara, including a relatively early cluster from the east of the archipelago. Our results are compatible with a polyphasic and polydirectional invasion of Nusa Tenggara by Rattus, likely beginning with RrC from the west to the east, an expansion of R. exulans from Flores, seemingly in no preferred overall direction, and finally the invasion of R. argentiventer from the east to the west. We find some support for the Dong Son drum maritime exchange network contributing to the distribution of the latter species.

Urbanisation alters landscapes, introduces wildlife to novel stressors, and fragments habitats into remnant ‘islands’. Within these islands, isolated wildlife populations can experience genetic drift and subsequently suffer from inbreeding depression and reduced adaptive potential. The Western tiger snake (Notechis scutatus occidentalis) is a predator of wetlands in the Swan Coastal Plain, a unique bioregion that has suffered substantial degradation through the development of the city of Perth, Western Australia. Within the urban matrix, tiger snakes now only persist in a handful of wetlands where they are known to bioaccumulate a suite of contaminants, and have recently been suggested as a relevant bioindicator of ecosystem health. Here, we used genome-wide single nucleotide polymorphism (SNP) data to explore the contemporary population genomics of seven tiger snake populations across the urban matrix. Specifically, we used population genomic structure and diversity, effective population sizes (Ne), and heterozygosity-fitness correlations to assess fitness of each population with respect to urbanisation. We found that population genomic structure was strongest across the northern and southern sides of a major river system, with the northern cluster of populations exhibiting lower heterozygosities than the southern cluster, likely due to a lack of historical gene flow. We also observed an increasing signal of inbreeding and genetic drift with increasing geographic isolation due to urbanisation. Effective population sizes (Ne) at most sites were small (< 100), with Ne appearing to reflect the area of available habitat rather than the degree of adjacent urbanisation. This suggests that ecosystem management and restoration may be the best method to buffer the further loss of genetic diversity in urban wetlands. If tiger snake populations continue to decline in urban areas, our results provide a baseline measure of genomic diversity, as well as highlighting which ‘islands’ of habitat are most in need of management and protection.

Speedy Genetic Diagnosis Infantile encephalopathy is associated with approximately 1500 genetic diseases. Without prompt treatment, permanent neurologic injury or death may occur. Here, the genome ...

version 2; peer review: 2 approved; International audience; We describe here a protocol for the generation of sequence-ready libraries for population epigenomics studies, and the analysis of alignment results. We show that the protocol can be used to monitor chromatin structure changes in populations when exposed to environmental cues. The protocol is a streamlined version of the Assay for transposase accessible chromatin with high-throughput sequencing (ATAC-seq) that provides a positive display of accessible, presumably euchromatic regions. The protocol is straightforward and can be used with small individuals such as daphnia and schistosome worms, and probably many other biological samples of comparable size (~10,000 cells), and it requires little molecular biology handling expertise.

Phenotypic plasticity is an important feature of biological systems that is likely to play a major role in the future adaptation of organisms to the ongoing global changes. It may allow an organism to produce alternative phenotypes in responses to environmental cues. Modifications in the phenotype can be reversible but are sometimes enduring and can even span over generations. The notion of phenotypic plasticity was conceptualized in the early 20thcentury by Richard Woltereck. He introduced the idea that the combined relations of a phenotypic character and all environmental gradients that influence on it can be defined as “norm of reaction”. Norms of reaction are specific to species and to lineages within species, and they are heritable. He postulated that reaction norms can progressively be shifted over generations depending on the environmental conditions. One of his biological models was the water-fleedaphnia. Woltereck proposed that enduring phenotypic modifications and gene mutations could have similar adaptive effects, and he postulated that their molecular bases would be different. Mutations occurred in genes, while enduring modifications were based on something he called theMatrix. He suggested that this matrix (i) was associated with the chromosomes, (ii) that it was heritable, (iii) it changed during development of the organisms, and (iv) that changes of the matrix could be simple chemical substitutions of an unknown, but probably polymeric molecule. We reasoned that the chromatin has all postulated features of this matrix and revisited Woltereck’s classical experiments withdaphnia. We developed a robust and rapid ATAC-seq technique that allows for analyzing chromatin of individual daphnia and show here (i) that this technique can be used with minimal expertise in molecular biology, and (ii) we used it to identify open chromatin structure in daphnia exposed to different environmental cues. Our result indicates that chromatin structure changes consistently in daphnia upon this exposure confirming Woltereck’s classical postulate.

We describe a new species of turtle-headed sea snake Emydocephalus orarius sp. nov. (Elapidae) from Western Australia’s Coral Coast, Pilbara and Kimberley regions. Phylogenetic analysis of mitochondrial markers places the new species as the sister lineage to the two currently recognised species in Emydocephalus: E. annulatus from the Timor Sea reefs and Coral Sea, and E. ijimae from the Ryukyu Islands. Analysis of nuclear SNP data from the new species and E. annulatus from Australia and New Caledonia provides additional independent evidence of their evolutionary distinctiveness. The new taxon is usually morphologically diagnosable from its congeners using a combination of scalation and colour pattern characters, and appears to reach greater total lengths (>1 m in the new species versus typically ~80 cm in E. annulatus/E. ijimae). The new species is known largely from soft-bottomed trawl grounds, unlike E. annulatus and E.ijimae which usually inhabit coral reefs. The discovery of this new species brings the number of sea snake species endemic to Western Australia to six.

Chickens (Gallus gallus domesticus) from the Americas have long been recognized as descendants of European chickens, transported by early Europeans since the fifteenth century. However, in recent years, a possible pre-Columbian introduction of chickens to South America by Polynesian seafarers has also been suggested. Here, we characterize the mitochondrial control region genetic diversity of modern chicken populations from South America and compare this to a worldwide dataset in order to investigate the potential maternal genetic origin of modern-day chicken populations in South America. The genetic analysis of newly generated chicken mitochondrial control region sequences from South America showed that the majority of chickens from the continent belong to mitochondrial haplogroup E. The rest belongs to haplogroups A, B and C, albeit at very low levels. Haplogroup D, a ubiquitous mitochondrial lineage in Island Southeast Asia and on Pacific Islands is not observed in continental South America. Modern-day mainland South American chickens are, therefore, closely allied with European and Asian chickens. Furthermore, we find high levels of genetic contributions from South Asian chickens to those in Europe and South America. Our findings demonstrate that modern-day genetic diversity of mainland South American chickens appear to have clear European and Asian contributions, and less so from Island Southeast Asia and the Pacific Islands. Furthermore, there is also some indication that South Asia has more genetic contribution to European chickens than any other Asian chicken populations.

Translocation is an increasingly common component of species conservation efforts. However, translocated populations often suffer from loss of genetic diversity and increased inbreeding, and thus may require active management to establish gene flow across isolated populations. Assisted gene flow can be laborious and costly, so recipient and source populations should be carefully chosen to maximise genetic diversity outcomes. The greater stick-nest rat (GSNR, Leporillus conditor), a threatened Australian rodent, has been the focus of a translocation program since 1985, resulting in five extant translocated populations (St Peter Island, Reevesby Island, Arid Recovery, Salutation Island and Mt Gibson), all derived from a remnant wild population on the East and West Franklin Islands. We evaluated the genetic diversity in all extant GSNR populations using a large single nucleotide polymorphism dataset with the explicit purpose of informing future translocation planning. Our results show varying levels of genetic divergence, inbreeding and loss of genetic diversity in all translocated populations relative to the remnant source on the Franklin Islands. All translocated populations would benefit from supplementation to increase genetic diversity, but two—Salutation Island and Mt Gibson—are of highest priority. We recommend a targeted admixture approach, in which animals for supplementation are sourced from populations that have low relatedness to the recipient population. Subject to assessment of contemporary genetic diversity, St Peter Island and Arid Recovery are the most appropriate source populations for genetic supplementation. Our study demonstrates an effective use of genetic surveys for data-driven management of threatened species.

The dormice (Gliridae) are a family of rodents represented by relatively few extant species, though the family was much more species-rich during the Early Miocene. Intergeneric phylogenetic relationships among glirids in some cases remain unresolved, despite extensive molecular and morphological analyses. Uncertainty is greatest with respect to the relationships among fossil taxa and how extinct lineages are related to modern species. The fossil genus Hypnomys from the Balearic Islands (western Mediterranean Sea) includes the Late Pleistocene–Holocene species Hypnomys morpheus, which has variously been considered a close relative or subgenus of the extant Eliomys. In the present study, we sequenced ancient mitochondrial DNA from H. morpheus, which suggests a sister relationship with the extant members of Eliomys. In addition, the pairwise sequence variation between Hypnomys and Eliomys is higher than that observed between congeneric glirid species (e.g., many Graphiurus spp.), which allows us to reject the hypothesis that Hypnomys is a subgenus of Eliomys. Our molecular dating analyses suggest that Hypnomys and Eliomys diverged 13.67 million years ago (95% highest posterior density [HPD] = 7.39–20.07). The relatively early split between these genera together with the molar morphology of early representatives of Hypnomys points to a Middle-Late Miocene origin from a continental glirid with a complex molar pattern, such as Vasseuromys or a closely related genus., This research was supported by a Marie Curie International Outgoing Fellowship within the 7th European Community Framework Programme (project MEDITADNA, PIOF‐GA‐2011‐300854, FP7‐PEOPLE), and it is included in the Research Project CGL2016‐79795, [“Cambios holocénicos en la biodiversidad animal de las islas de la Macaronesia y de Baleares. II,” CGL2016‐80000‐P (Dirección General de Investigación Científica y Técnica, Ministerio de Economía y Competitividad)] and SGR2017‐859 (AGAUR, Gencat).

Reintroduction programs aim to restore self-sustaining populations of threatened species to their historic range. However, demographic restoration may not reflect genetic restoration, which is necessary for the long-term persistence of populations. Four threatened Australian mammals, the greater stick-nest rat (Leporillus conditor), greater bilby (Macrotis lagotis), burrowing bettong (Bettongia lesueur) and western barred bandicoot (Perameles bougainville), were reintroduced at Arid Recovery Reserve in northern South Australia over the last 18 years. These reintroductions have been deemed successful based on population growth and persistence, however the genetic consequences of the reintroductions are not known. We generated large single nucleotide polymorphism (SNP) datasets for each species currently at Arid Recovery and compared them to samples collected from founders. We found that average genetic diversity in all populations at the Arid Recovery Reserve are close to, or exceeding, the levels measured in the founders. Increased genetic diversity in two species was achieved by admixing slightly diverged and inbred source populations. Our results suggest that genetic diversity in translocated populations can be improved or maintained over relatively long time frames, even in small conservation reserves, and highlight the power of admixture as a tool for conservation management.

The distribution of antilopine wallaroo, Macropus antilopinus, is marked by a break in the species’ range between Queensland and the Northern Territory, coinciding with the Carpentarian barrier. Previous work on M. antilopinus revealed limited genetic differentiation between the Northern Territory and Queensland M. antilopinus populations across this barrier. The study also identified a number of divergent lineages in the Northern Territory, but was unable to elucidate any geographic structure. Here, we re‐examine these results to (1) determine phylogeographic patterns across the range of M. antilopinus and (2) infer the biogeographic barriers associated with these patterns. The tropical savannahs of northern Australia: from the Cape York Peninsula in the east, to the Kimberley in the west. We examined phylogeographic patterns in M. antilopinus using a larger number of samples and three mtDNA genes: NADH dehydrogenase subunit 2, cytochrome b, and the control region. Two datasets were generated and analyzed: (1) a subset of samples with all three mtDNA regions concatenated together and (2) all samples for just control region sequences that included samples from the previous study. Analysis included generating phylogenetic trees based on Bayesian analysis and intraspecific median‐joining networks. The contemporary spatial structure of M. antilopinus mtDNA lineages revealed five shallow clades and a sixth, divergent lineage. The genetic differences that we found between Queensland and Northern Territory M. antilopinus samples confirmed the split in the geographic distribution of the species. We also found weak genetic differentiation between Northern Territory samples and those from the Kimberley region of Western Australia, possibly due to the Kimberley Plateau–Arnhem Land barrier. Within the Northern Territory, two clades appear to be parapatric in the west, while another two clades are broadly sympatric across the Northern Territory. MtDNA diversity of M. antilopinus revealed an unexpectedly complex evolutionary history involving multiple sympatric and parapatric mtDNA clades across northern Australia. These phylogeographic patterns highlight the importance of investigating genetic variation across distributions of species and integrating this information into biodiversity conservation.

Myotragus balearicus was the last living representative of an extinct caprine lineage endemic to the Balearic Islands (Western Mediterranean), which became extinct following the arrival of humans around 4300 years ago. The tribal attribution of Myotragus based on morphological analyses has been complicated due to its unusual morphological characteristics, though most studies agree on its inclusion within Caprini (also including modern sheep and goats). Analyses of short fragments of ancient mitochondrial DNA have suggested Ovis (comprising extant sheep) as sister taxon to Myotragus, although other authors have suggested alternative placements within Caprini using the same data. In the present study, we present a complete high-depth mitochondrial genome of M. balearicus, which allowed us to test the previously proposed Ovis/Myotragus clade and revealed a closer relationship between Myotragus and the takin (Budorcas taxicolor). The results of our molecular clock analyses suggested that the split between Myotragus and Budorcas occurred around 7.1 Mya, which is compatible with the arrival of the ancestor of Myotragus to the Balearic Islands during the Messinian Salinity Crisis (5.97–5.33 Mya). We also conducted a preliminary phylogeographic analysis of M. balearicus in Mallorca, which revealed weak spatial and temporal structure within the population during the Holocene., This research was supported by a Marie Curie International Outgoing Fellowship within the 7th European Community Framework Programme (project MEDITADNA, PIOF-GA-2011-300854, FP7-PEOPLE) (Pere Bover), and Australian Research Council Laureate and Discovery Project funding (Alan Cooper). This work is also integrated within the research project CGL2016–79795-R (Josep A. Alcover). Pere Bover has a research contract from the Fundación Agencia Aragonesa para la Investigación y el Desarrollo (ARAID).

We describe a new species of Rattus , from 3 modern specimens collected on Manus Island in the Admiralty Group, Papua New Guinea, between 2002 and 2012. Subfossil specimens of early to late Holocene age from the Pamwak archaeological site on Manus Island are referred to the new species on morphological criteria; these confirm the species as a long-term resident of Manus Island. The new species is distinguished by its combination of large size; short tail; dorsal pelage that is coarse, spiny, and dark, with prominent black guard hairs; and sharply contrasting cream ventral pelage. Based on its overall body form, the species is almost certainly terrestrial. The dentition combines robust incisors with relatively small molars and the cranium displays a distinctive melange of characters—including an elongate and anteriorly expanded rostrum and a mesopterygoid fossa that is narrow anteriorly and broadens to the rear. Sequence data from the mitochondrial control region and 3 nuclear genes place the new species as a highly divergent member of the Australo–Papuan Rattus radiation, with no identified close relative among sampled taxa. Morphological comparisons are made between the new species and other pertinent species of Rattus from the region, including R. sanila , a species known only from Late Pleistocene fossil to Late Holocene subfossil remains from an archaeological site on New Ireland. The conservation status of the new species is discussed in the light of a recent survey that failed to locate surviving populations in 2 areas of natural forest on Manus Island. Further survey work is urgently needed to identify any surviving populations and to assess the role of potential threats to the species.

The murid rodent genus Rattus Fischer 1803 contains several species that are responsible for massive loss of crops and food, extinction of other species and the spread of zoonotic diseases to humans, as well as a laboratory species used to answer important questions in physiology, immunology, pharmacology, toxicology, nutrition, behaviour and learning. Despite the well-known significant impacts of Rattus, a definitive evolutionary based systematic framework for the genus is not yet available. The past 75 years have seen more dramatic changes in membership of Rattus than in almost any other genus of mammals. In fact, the Rattus genus has been a receptacle for any generalised Old World murine that lacked morphological specialisation and at one point, has included more than 560 species and/or subspecies, spread across Eurasia, Africa and the Australo-Papuan region. The dissolution of Rattus is ongoing as many of its constituent species and many genera of Rattini remain unsampled in any molecular study. To address this sampling limitation, we sequenced the mitochondrial cytochrome b (cytb) gene and examined phylogenetic relationships using both Bayesian and Maximum Likelihood algorithms for an expanded set of taxa within Rattus and among closely related genera. Here we place previously unsampled taxa in a phylogenetic context for the first time, including R. burrus, R. hoogerwerfi, R. lugens, and R. mindorensis within the Asian Rattus group, R. facetus within the Australo-Papuan Rattus radiation, and the undescribed ‘Bisa Rat’ described by Flannery as sister to the recently described genus Halmaheramys. We also present an exploratory foray into the wider topic of Rattus phylogenetics and propose that a reorganisation of the Rattus genus should require that it be a monophyletic group, include at least the type species R. norvegicus and R. rattus (plus their close allies); and exclude the Bandicota/Nesokia clade and other such specialised genera.

The musk ox (Ovibos moschatus) is the only surviving member of a group of Pleistocene North American musk ox genera (Praeovibos, Ovibos, Bootherium, Euceratherium, and Soergelia) whose taxonomy is uncertain. The helmeted musk ox (Bootherium bombifrons) and the woodland musk ox (Symbos cavifrons) have been synonymised as male and female forms of a single Nearctic species found from Alaska, in the north, to Texas, in the south. However, this reclassification has not been tested using molecular data, despite the potential to use ancient DNA to examine these late Pleistocene taxa. In the present study, we sequenced mitochondrial genomes from seven subfossil musk ox specimens (originally identified as Bootherium and/or Symbos), allowing us to evaluate the identity of these muskoxen, explore their phylogeography, and estimate the timeline for their evolution. We also used nuclear genomic data to determine the sex of six of our seven samples. Ultimately, our molecular data support the synonymisation of the North American muskoxen Bootherium and Symbos.

Parthenogenesis is a form of asexual reproduction by which embryos develop from unfertilized eggs. Parthenogenesis occurs in reptiles; however, it is not yet known to occur in the widespread elapid snakes (Elapidae), which include well-known taxa such as cobras, mambas, taipans and sea snakes. Here, we describe the production of viable parthenogens in two species of Australo-Papuan elapids with divergent reproductive modes: the oviparous coastal/Papuan taipan ( Oxyuranus scutellatus ) and the viviparous southern death adder ( Acanthophis antarcticus ). Analyses of nuclear SNP data excluded paternity for putative fathers and convincingly demonstrated asexual reproduction, thus representing the first evidence of facultative parthenogenesis in Elapidae. Our finding has broad implications for understanding the evolution of reproductive diversity in snakes, as well as managing the conservation of genetic diversity in wild and captive populations.

The occurrence of black fur, or melanism, in many mammalian species is known to be linked to DNA sequence variation in the agouti signaling protein (Asip) gene, which is a major determinant of eumelanin and pheomelanin pigments in coat color. We investigated 38 agouti (i.e., banded wildtype) and four melanistic Rattus rattus species complex (RrC) lineage II specimens from Okinawa Island, Ryukyu Islands, Japan, for genetic variation in three exons and associated flanking regions in the Asip gene. On Okinawa, a predicted loss-of-function mutation caused by a cysteine to serine amino acid change at p.124C>S (c.370T>A) in the highly conserved functional domain of Asip was found in melanistic rats, but was absent in agouti specimens, suggesting that the p.124C>S mutation is responsible for the observed melanism. Phylogeographic analysis found that Asip sequences from Okinawan RrC lineage II, including both agouti and melanistic specimens, differed from: 1) both agouti and melanistic RrC lineage I from Otaru, Hokkaido, Japan, and 2) agouti RrC lineages I and II from South Australia. This suggests the possibility of in-situ mutation of the Asip gene, either within the RrC lineage II population on Okinawa or in an unsampled RrC lineage II population with biogeographic links to Okinawa, although incomplete lineage sorting could not be ruled out.

Understanding the evolution of Australia's extinct marsupial megafauna has been hindered by a relatively incomplete fossil record and convergent or highly specialized morphology, which confound phylogenetic analyses. Further, the harsh Australian climate and early date of most megafaunal extinctions (39-52 ka) means that the vast majority of fossil remains are unsuitable for ancient DNA analyses. Here, we apply cross-species DNA capture to fossils from relatively high latitude, high altitude caves in Tasmania. Using low-stringency hybridization and high-throughput sequencing, we were able to retrieve mitochondrial sequences from two extinct megafaunal macropodid species. The two specimens, Simosthenurus occidentalis (giant short-faced kangaroo) and Protemnodon anak (giant wallaby), have been radiocarbon dated to 46-50 and 40-45 ka, respectively. This is significantly older than any Australian fossil that has previously yielded DNA sequence information. Processing the raw sequence data from these samples posed a bioinformatic challenge due to the poor preservation of DNA. We explored several approaches in order to maximize the signal-to-noise ratio in retained sequencing reads. Our findings demonstrate the critical importance of adopting stringent processing criteria when distant outgroups are used as references for mapping highly fragmented DNA. Based on the most stringent nucleotide data sets (879 bp for S. occidentalis and 2,383 bp for P. anak), total-evidence phylogenetic analyses confirm that macropodids consist of three primary lineages: Sthenurines such as Simosthenurus (extinct short-faced kangaroos), the macropodines (all other wallabies and kangaroos), and the enigmatic living banded hare-wallaby Lagostrophus fasciatus (Lagostrophinae). Protemnodon emerges as a close relative of Macropus (large living kangaroos), a position not supported by recent morphological phylogenetic analyses.

The red-toothed shrews (Soricinae) are the most widespread subfamily of shrews, distributed from northern South America to North America and Eurasia. Within this subfamily, the tribe Nectogalini includes the fossil species Nesiotites hidalgo recorded from the Late Pleistocene to Holocene of the Balearic Islands (Western Mediterranean). Although there is a consensus about the close relationship between the extinct red-toothed shrew genera Nesiotites and Asoriculus based on morphology, molecular data are necessary to further evaluate the phylogenetic relationships of the Balearic fossils. We obtained a near complete mitochondrial genome of N. hidalgo, allowing the first molecular phylogenetic analysis of this species. Analyses based on 15,167 bp of the mitochondrial genome placed N. hidalgo as close relative to the extant Himalayan shrew (Soriculus nigrescens), and a combined analysis using molecular and morphological data confirm that N. hidalgo and Asoriculus gibberodon are sister-taxa with S. nigrescens as the immediate outgroup. Molecular clock and divergence estimates suggest that the split between N. hidalgo and its closest living relative occurred around 6.44 Ma, which is in agreement with the previously proposed colonisation of the Balearic Islands from mainland Europe by nectogaline shrews during the Messinian Salinity Crisis (5.97–5.33 My ago). Our results highlight that it is possible to retrieve genetic data from extinct small mammals from marginal environments for DNA preservation. Additional finds from the fossil record of Soricinae from the Eurasian Late Miocene/Early Pliocene are needed to shed further light on the still confusing taxonomy and paleobiogeography of this clade.

Research on changes in phenotypic plasticity within wild animal populations is centuries old, however far fewer studies have investigated the role that epigenetics play in the development or persistence of natural variation in response to environmental change. Tiger snakes (Notechis scutatus) are an ideal study organism to investigate the link between epigenetics and phenotypic responses to environmental change, as they live on a range of offshore islands with different environments and prey types while exhibiting gigantism and dwarfism in body and head size. In this study, we have generated methylation sensitive amplified polymorphism (MSAP) data and found that, in general, Tiger Snakes are more epigenetically differentiated than genetically differentiated. Each island group has a distinctive epigenetic signal, suggesting the Tiger Snakes on each island group have adapted to their specific environment. This is also supported by the strong positive relationship between epigenetic differentiation and isolation age, as well as between epigenetic/genetic signal and both temperature and precipitation. The Tiger Snakes from Kangaroo Island, which has a complex landscape/environment like the mainland rather than the simple landscape/environment of each of the smaller islands, are both genetically and epigenetically more like the mainland. As the MSAP loci are randomly distributed across the genome, we believe a closer examination of the epigenetic modifications near genes involved in growth, development, and lipid metabolism will allow us to investigate the epigenetic basis for the natural variation in head size and body size on the islands.

Australia's iconic emu (Dromaius novaehollandiae novaehollandiae) is the only living representative of its genus, but fossil evidence and reports from early European explorers suggest that three island forms (at least two of which were dwarfs) became extinct during the nineteenth century. While one of these—the King Island emu—has been found to be conspecific with Australian mainland emus, little is known about how the other two forms—Kangaroo Island and Tasmanian emus—relate to the others, or even the size of Tasmanian emus. We present a comprehensive genetic and morphological analysis ofDromaiusdiversity, including data from one of the few definitively genuine Tasmanian emu specimens known. Our genetic analyses suggest that all the island populations represent sub-populations of mainlandD.novaehollandiae. Further, the size of island emus and those on the mainland appears to scale linearly with island size but not time since isolation, suggesting that island size—and presumably concomitant limitations on resource availability—may be a more important driver of dwarfism in island emus, though its precise contribution to emu dwarfism remains to be confirmed.

Little is known about the determinants of females' social interactions in species with fission–fusion social organization, in which individuals associate with different individuals at different times. Even less is known about social organization in marsupials. We investigated the association patterns of wild female eastern grey kangaroos in southeast Queensland. Female kangaroos had a nonrandom social structure and we present a new methodology for analysing social structure that accounts for the amount of spatial overlap shared by pairs of female kangaroos. This simulation model showed that patterns of association among our female kangaroos were not simply those predicted by their patterns of spatial overlap. Females that associated frequently with certain associates were able to graze for longer because they were less vigilant, and thus were able to benefit from having frequent associates. Female kangaroo social structure was affected by the loss of key members of the society during a period of unusually high predation. Information-theoretical modelling showed that the factors affecting grazing behaviour changed after partial population turnover, with the strength of association between nearest neighbours having a positive effect on grazing behaviour before population turnover and group size having a positive effect on grazing behaviour after population turnover. We propose that social organization within this marsupial is more structured than previously thought.

A magnetic anomaly is produced when a rock unit has a magnetic contrast with a laterally adjacent rock unit. The cause of this magnetic contrast might be produced by a change in the magnetic susceptibility and/or magnetic remanence of the source bodies. After Vine and Matthews (1963) demonstrated that magnetic anomalies observed over ocean basins record a chronology of ocean floor generation, it was readily apparent that in some instances the genesis of a magnetic anomaly can be dominated by the remanence component. Surprisingly, few investigators have acknowledged that magnetic remanence can have a similar influence on continental magnetic anomalies. The incorporation of magnetic remanence data into a magnetic inversion scheme continues to present a major problem. In this note, we outline the problem and present some approaches that might be used to derive relevant remanence information.

The colonization of Madagascar by Austronesian-speaking people during AD 50–500 represents the most westerly point of the greatest diaspora in prehistory. A range of economically important plants and animals may have accompanied the Austronesians. Domestic chickens ( Gallus gallus ) are found in Madagascar, but it is unclear how they arrived there. Did they accompany the initial Austronesian-speaking populations that reached Madagascar via the Indian Ocean or were they late arrivals with Arabian and African sea-farers? To address this question, we investigated the mitochondrial DNA control region diversity of modern chickens sampled from around the Indian Ocean rim (Southeast Asia, South Asia, the Arabian Peninsula, East Africa and Madagascar). In contrast to the linguistic and human genetic evidence indicating dual African and Southeast Asian ancestry of the Malagasy people, we find that chickens in Madagascar only share a common ancestor with East Africa, which together are genetically closer to South Asian chickens than to those in Southeast Asia. This suggests that the earliest expansion of Austronesian-speaking people across the Indian Ocean did not successfully introduce chickens to Madagascar. Our results further demonstrate the complexity of the translocation history of introduced domesticates in Madagascar.

None of the letters in response to Thomson et al. (1) undermine our conclusions. However, several issues have been raised, which we address in this reply. Beavan (2) dismisses some of the concerns that have been raised about the accuracy of the radiocarbon dates of the El Arenal-1 chicken bones, which are immediately pre-Columbian. Although procedures, such as ultrafiltration of amino acids, are common practice for suboptimal bone samples, such as the oldest El Arenal-1 sample, further complex issues, including dietary sources and the potential for indirect marine carbon input (3), mean that a detailed assessment of the site through multiple further dates would be required to exclude the possibility that the specimens might actually be post-Columbian. This approach seems particularly advisable given that analogous issues were raised about a surprisingly early date for New Zealand colonization based on Pacific rat bone dates …

The human colonization of Remote Oceania remains one of the great feats of exploration in history, proceeding east from Asia across the vast expanse of the Pacific Ocean. Human commensal and domesticated species were widely transported as part of this diaspora, possibly as far as South America. We sequenced mitochondrial control region DNA from 122 modern and 22 ancient chicken specimens from Polynesia and Island Southeast Asia and used these together with Bayesian modeling methods to examine the human dispersal of chickens across this area. We show that specific techniques are essential to remove contaminating modern DNA from experiments, which appear to have impacted previous studies of Pacific chickens. In contrast to previous reports, we find that all ancient specimens and a high proportion of the modern chickens possess a group of unique, closely related haplotypes found only in the Pacific. This group of haplotypes appears to represent the authentic founding mitochondrial DNA chicken lineages transported across the Pacific, and allows the early dispersal of chickens across Micronesia and Polynesia to be modeled. Importantly, chickens carrying this genetic signature persist on several Pacific islands at high frequencies, suggesting that the original Polynesian chicken lineages may still survive. No early South American chicken samples have been detected with the diagnostic Polynesian mtDNA haplotypes, arguing against reports that chickens provide evidence of Polynesian contact with pre-European South America. Two modern specimens from the Philippines carry haplotypes similar to the ancient Pacific samples, providing clues about a potential homeland for the Polynesian chicken.

Commensal plants and animals have long been used to track human migrations, with Rattus exulans (the Pacific rat) a common organism for reconstructing Polynesian dispersal in the Pacific. However, with no knowledge of the homeland of R. exulans, the place of origin of this human-commensal relationship is unknown. We conducted a mitochondrial DNA phylogeographic survey of R. exulans diversity across the potential natural range in mainland and Island Southeast Asia in order to establish the origin of this human-commensal dyad. We also conducted allozyme electrophoresis on samples from ISEA to obtain a perspective on patterns of genetic diversity in this critical region. Finally, we compared molecular genetic evidence with knowledge of prehistoric rodent faunas in mainland and ISEA. We find that ISEA populations of R. exulans contain the highest mtDNA lineage diversity including significant haplotype diversity not represented elsewhere in the species range. Within ISEA, the island of Flores in the Lesser Sunda group contains the highest diversity in ISEA (across all loci) and also has a deep fossil record of small mammals that appears to include R. exulans. Therefore, in addition to Flores harboring unusual diversity in the form of Homo floresiensis, dwarfed stegodons and giant rats, this island appears to be the homeland of R. exulans.

The living hyena species (spotted, brown, striped and aardwolf) are remnants of a formerly diverse group of more than 80 fossil species, which peaked in diversity in the Late Miocene (about 7-8 Ma). The fossil history indicates an African origin, and morphological and ancient DNA data have confirmed that living spotted hyenas (Crocuta crocuta) of Africa were closely related to extinct Late Pleistocene cave hyenas from Europe and Asia. The current model used to explain the origins of Eurasian cave hyena populations invokes multiple migrations out of Africa between 3.5-0.35 Ma. We used mitochondrial DNA sequences from radiocarbon-dated Chinese Pleistocene hyena specimens to examine the origin of Asian populations, and temporally calibrate the evolutionary history of spotted hyenas. Our results support a far more recent evolutionary timescale (430-163 kya) and suggest that extinct and living spotted hyena populations originated from a widespread Eurasian population in the Late Pleistocene, which was only subsequently restricted to Africa. We developed statistical tests of the contrasting population models and their fit to the fossil record. Coalescent simulations and Bayes Factor analysis support the new radiocarbon-calibrated timescale and Eurasian origins model. The new Eurasian biogeographic scenario proposed for the hyena emphasizes the role of the vast steppe grasslands of Eurasia in contrast to models only involving Africa. The new methodology for combining genetic and geological data to test contrasting models of population history will be useful for a wide range of taxa where ancient and historic genetic data are available.

This case study describes how a mother with a congenital below-elbow limb absence manages breastfeeding and child care. Information for the case study was gained from direct observation, detailed interviews, and the subject's written reflections. Literature review revealed that, worldwide, many women have upper limb deficiencies. Such deficits may occur congenitally from teratogens or other causes, or they may occur as a result of disease or trauma. In spite of recent technological advances, prostheses are restricted in their efficiency and are not frequently used. Support from others is a critical factor in enabling those with limb deficiencies to achieve an optimal quality of life, including during childbearing and childrearing. No published data to assist breastfeeding mothers with limb deficiencies was revealed. Specific practices are mentioned that promote self-confidence and capability with breastfeeding and fulfilling children's needs.

Dispersal reduces the likelihood of inbreeding and maintains gene flow among populations. Many polygynous mammals exhibit male-biased dispersal with female philopatry. Previous observational studies of eastern grey kangaroos (Macropus giganteus) suggested female philopatry while genetic studies showed weak structuring. We tested for sex-biased dispersal using two Queensland populations of kangaroos: one in Sundown National Park and the second at Elanda Point, Australia. Samples from 25 females and 23 males were collected from Sundown National Park, and analysed for partial mtDNA control region sequences (n = 47) and genotypes based on 12 microsatellite loci (n = 41). Samples from 18 males and 22 females from Elanda Point were genotyped at 8 loci and a subset sequenced for mtDNA (n = 19). Analyses showed higher mtDNA haplotype and nucleotide diversity in males than females within both populations, genetic relatedness based on microsatellite data was significantly higher among females, and microsatellite allelic richness was higher in males, suggesting that females are more likely to be philopatric and males more likely to disperse. These findings reinforce the value of including multiple types of genetic markers in dispersal analyses as mtDNA results showed higher male diversity (suggesting male dispersal) but males also contributed microsatellite alleles to the local population, masking differentiation between the sexes and confounding analyses.

Oropharyngeal mucositis is a frequent, severe complication of local irradiation for tumours in the head and neck. We postulated that heated humidification of inspired air via a nasal interface may palliate symptoms of mucositis by reducing the discomfort associated with dry, sticky secretions. We sought to review the effect of home-based humidification on hospital admissions and the patient reported experience of that humidification.This study was a retrospective review. A historical (control) group of patients did not receive home humidification at any stage (n = 55) and a study group (n = 53) received home humidification at or after the onset of grade 3 mucositis. A questionnaire was sent to study group patients to obtain information about their experience of using the humidifier at home.There were no demographic differences between the study and control groups, but the study group had significantly more advanced cancer (stage IV; p = .0307) and significantly higher total fractions and days treated (p.01). Group comparison showed no difference in subsequent overall hospital admissions (p = .9269), but 7 of the 55 control group patients (12.7%) were admitted for supportive care within 2 months of completing radiotherapy, whereas none of the 53 patients who used home humidification were admitted after starting that use (p.01). Almost all (95%) of the study group patients reported that humidification was of benefit, and 81% stated that it relieved mouth or throat pain.Humidification of inspired gas offers a simple, drug-free option for managing a number of the adverse mucosal effects of radiation and chemoradiation in head and neck cancer patients.

Phylogeographic studies around the world have identified refugia where fauna were able to persist during unsuitable climatic periods, particularly during times of glaciation. In Australia the effects of Pleistocene climate oscillations on rainforest taxa have been well studied but less is known about the effects on mesic-habitat fauna, such as the eastern grey kangaroo (Macropus giganteus). The eastern grey kangaroo is a large mammal that is common and widespread throughout eastern Australia, preferring dry mesic habitat, rather than rainforest. As pollen evidence suggests that the central-eastern part of Australia (southeast Queensland and northern New South Wales) experienced cycles of expansion in mesic habitat with contraction in rainforests, and vice versa during glacial and interglacial periods, respectively, we hypothesise that the distribution of the eastern grey kangaroo was affected by these climate oscillations and may have contracted to mesic habitat refugia. From 375 mitochondrial DNA control region sequences from across the distribution of eastern grey kangaroos we obtained 108 unique haplotypes. Phylogenetic analysis identified two clades in Queensland, one of which is newly identified and restricted to a small coastal region in southern Queensland north of Brisbane, known as the Sunshine Coast. The relatively limited geographic range of this genetically isolated clade suggests the possibility of a mesic habitat refugium forming during rainforest expansion during wetter climate cycles. Other potential, although less likely, reasons for the genetic isolation of the highly distinct clade include geographic barriers, separate northward expansions, and strong local adaptation.