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Accounting for historical demographic features is vital for many types of evolutionary inferences, including the estimation of divergence times between closely related populations. In barn swallow, Hirundo rustica, inferring historical population sizes and subspecies divergence times can shed light on the recent co-evolution of this species with humans. Pairwise sequentially Markovian coalescent uncovered population growth beginning on the order of one million years ago-which may reflect the radiation of the broader Hirundo genus-and a more recent population decline. Additionally, we used approximate Bayesian computation to evaluate hypotheses about recent timescale barn swallow demography, including population growth due to human commensalism, and a potential founder event associated with the onset of nesting on human structures. We found signal for a bottleneck event approximately 7,700 years ago, near the time that humans began building substantial structures, although there was considerable uncertainty associated with this estimate. Subspecies differentiation and subsequent growth occurred after the bottleneck in the best-supported model, an order of magnitude more recently than previous estimates in this system. We also compared results obtained from whole-genome sequencing versus reduced representation sequencing, finding many similar results despite substantial allelic dropout in the reduced representation data, which may have affected estimates of some parameters. This study presents the first genetic evidence of a potential barn swallow founder effect and subspecies divergence coinciding with the Holocene, which is an important step in analysing the biogeographical history of a well-known human commensal species.

Repeated evolutionary events imply underlying genetic constraints that can make evolutionary mechanisms predictable. Morphological traits are thought to evolve frequently through cis-regulatory changes because these mechanisms bypass constraints in pleiotropic genes that are reused during development. In contrast, the constraints acting on metabolic traits during evolution are less well studied. Here we show how a metabolic bottleneck gene has repeatedly adopted similar cis-regulatory solutions during evolution, likely due to its pleiotropic role integrating flux from multiple metabolic pathways. Specifically, the genes encoding phosphoglucomutase activity (PGM1/PGM2), which connect GALactose catabolism to glycolysis, have gained and lost direct regulation by the transcription factor Gal4 several times during yeast evolution. Through targeted mutations of predicted Gal4-binding sites in yeast genomes, we show this galactose-mediated regulation of PGM1/2 supports vigorous growth on galactose in multiple yeast species, including Saccharomyces uvarum and Lachancea kluyveri. Furthermore, the addition of galactose-inducible PGM1 alone is sufficient to improve the growth on galactose of multiple species that lack this regulation, including Saccharomyces cerevisiae. The strong association between regulation of PGM1/2 by Gal4 even enables remarkably accurate predictions of galactose growth phenotypes between closely related species. This repeated mode of evolution suggests that this specific cis-regulatory connection is a common way that diverse yeasts can govern flux through the pathway, likely due to the constraints imposed by this pleiotropic bottleneck gene. Since metabolic pathways are highly interconnected, we argue that cis-regulatory evolution might be widespread at pleiotropic genes that control metabolic bottlenecks and intersections.

`It is well established that most new systemic infections of HIV-1 can be traced back to one or a limited number of founder viruses. Usually, these founders are more closely related to minor HIV-1 populations in the blood of the presumed donor than to more abundant lineages. This has led to the widely accepted idea that transmission selects for viral characteristics that facilitate crossing the mucosal barrier of the recipient's genital tract, although the specific selective forces or advantages are not completely defined. However, there are other steps along the way to becoming a founder virus at which selection may occur. These steps include the transition from the donor's general circulation to the genital tract compartment, survival within the transmission fluid, and establishment of a nascent stable local infection in the recipient's genital tract. Finally, there is the possibility that important narrowing events may also occur during establishment of systemic infection. This is suggested by the surprising observation that the number of founder viruses detected after transmission in intravenous drug users is also limited. Although some of these steps may be heavily selective, others may result mostly in a stochastic narrowing of the available founder pool. Collectively, they shape the initial infection in each recipient.

Naphthalene 1,2-dioxygenase (NDO) has been computationally understudied despite the extensive experimental knowledge obtained for this enzyme, including numerous crystal structures and over 100 demonstrated substrates. In this study, we have developed a substrate prediction model that moves away from the traditional active-site-centric approach to include the energetics of substrate entry into the active site. By comparison with experimental data, the accuracy of the model for predicting substrate oxidation is 92%, with a positive predictive value of 93% and a negative predictive value of 98%. Also, the present analysis has revealed that the amino acid residues that provided the largest energetic barrier for compounds entering the active site are residues F224, L227, P234, and L235. In addition, F224 is proposed to play a role in controlling ligand entrance via π-π stacking stabilization as well as providing stabilization via T-shaped π-π interactions once the ligand has reached the active-site cavity. Overall, we present a method capable of being scaled to computationally discover thousands of substrates of NDO, and we present parameters to be used for expanding the prediction method to other members of the Rieske non-heme iron oxygenase family.

The identification of population bottlenecks is critical in conservation because populations that have experienced significant reductions in abundance are subject to a variety of genetic and demographic processes that can hasten extinction. Genetic bottleneck tests constitute an appealing and popular approach for determining if a population decline has occurred because they only require sampling at a single point in time, yet reflect demographic history over multiple generations. However, a review of the published literature indicates that, as typically applied, microsatellite-based bottleneck tests often do not detect bottlenecks in vertebrate populations known to have experienced declines. This observation was supported by simulations that revealed that bottleneck tests can have limited statistical power to detect bottlenecks largely as a result of limited sample sizes typically used in published studies. Moreover, commonly assumed values for mutation model parameters do not appear to encompass variation in microsatellite evolution observed in vertebrates and, on average, the proportion of multi-step mutations is underestimated by a factor of approximately two. As a result, bottleneck tests can have a higher probability of 'detecting' bottlenecks in stable populations than expected based on the nominal significance level. We provide recommendations that could add rigor to inferences drawn from future bottleneck tests and highlight new directions for the characterization of demographic history.

The ability of a population to evolve in a changing environment may be compromised by human-imposed barriers to gene flow. We investigated the population structure and the possible occurrence of a genetic bottleneck in two isolated populations of the black-faced lion tamarin (Leontopithecus caissara), a species with very reduced numbers (less than 400) in a very restricted range in the Atlantic Forest of southeast Brazil. We determined the genotypes of 52 individuals across 9 microsatellite loci. We found genetic divergence between the populations, each exhibiting low genetic diversity. Analysis revealed broad- and fine-scale population structuring. Both populations have evidently experienced population reduction and a genetic bottleneck without presenting any apparent detrimental effect. Anyway, measures should be taken to effectively protect the forests where L. caissara occurs in order to allow its populations to increase and counteract the eventual effects of genetic impoverishment.

Information on the demographic and genetic consequences of overexploitation of large marine vertebrates is often difficult to demonstrate on ecological time scales. We investigate the genetic impacts of recent commercial activities along Mexico’s Pacific coast on the nesting colonies of a long-lived vertebrate of conservation concern, the olive ridley turtle (Lepidochelys olivacea). This species was severely impacted by a commercial fishery between 1960 and 1990 (e.g. >350,000 individuals were caught in a single year), depleting important nesting areas within few decades. Microsatellite DNA variation of 334 samples representing 18 nesting sites revealed a clear signature of recent bottlenecks associated with changes in allelic diversity. Consistent with theoretical expectations and other empirical studies, we found no evidence for bottlenecks based on measures of heterozygosity. The bottleneck signal was strong across the highly connected metapopulation and also apparent in six nesting sites in a pattern consistent with the history of demographic disequilibria produced by their overexploitation. In addition, we clarify population structure across Mexico and show that Mismaloya, a key colony where human harvest led to a dramatic change in the species’ reproduction mode, has not been supplemented by gene flow after the bottleneck and has diverged genetically from other demes. This is perhaps the first study to detect recent signatures of anthropogenic-driven population declines in sea turtles using genetics. This enables managers to consider information about genetic signatures of contemporary demographic changes during the development of conservation management plans and during population monitoring.

The isolated population of Rainbow Lorikeets (Trichoglossus haematodus) in Perth, Western Australia, was founded by fewer than 10 birds introduced in the early 1960s. I recorded vocalisations of individuals in Perth, and from >2000km away, at one site in South Australia and one in Victoria, to determine if the Perth population showed evidence of a founder effect in three common types of vocal signals. I measured spectral features of the calls of each recorded bird. Linear discriminant analysis indicated the three population samples differed significantly for all three call-types but there was no consistent trend suggesting the Perth birds retained evidence of a founder effect in these calls. Calls of Perth birds were not more simplified or more homogeneous in their acoustic traits. Although it is possible that there are founder effects for total vocal repertoires, which was not assessed here, there was no evidence for a founder effect in these most conspicuous vocalisations.

The Mbeya region of Tanzania has a genetically complex HIV epidemic with multiple subtypes and recombinant forms circulating, together with a high frequency of dual infections with more than one subtype. This study aimed to determine whether this impacted the HIV-1 transmission bottleneck. A total of 210 env sequences from 22 participants were generated from recently infected women from Mbeya using the single genome amplification approach. Participants were infected with subtypes C ( n = 9), A ( n = 4), or D ( n = 1), and recombinants AC ( n = 4), CD ( n = 2), AD ( n = 1), or ACD ( n = 1). Sixteen participants (73%) were infected with a single variant; five (23%) with multiple variants; and one (4%) was dually infected. Thus the frequency of single variant infections was similar to cohorts located in genetically restricted subtype B or C epidemics, suggesting that multiple circulating subtypes and unique recombinant forms do not have a significant impact on the transmission bottleneck.

The bottlenose dolphin (Tursiops truncatus) is the only resident marine mammal species in the Croatian part of the Adriatic Sea, with an estimated number at around 220 individuals. It is an endangered and legally protected species in Croatia, and its demographic history is poorly known. This study investigates the level of genetic diversity in the bottlenose dolphin population from the Croatian part of the Adriatic Sea and a possibility of recent population size contraction, since there are indications that there has been intensive eradication operations in the mid 20th century that might have caused reductions in the effective population size and might have resulted in a loss of genetic variation. Thirty samples were genotyped at 12 dinucleotide microsatellite loci. The mean allelic richness (6.835 ± 0.705) and mean expected heterozygosity (0.692 ± 0.05) revealed high level of genetic diversity. Bottleneck analysis gave ambiguous evidence for a recent population decline in the investigated bottlenose dolphin population. The M ratio test, with two sets of parameter values, suggested a recent bottleneck ; whereas the analysis by the Bottleneck program under three mutation models (TPM, SMM and IAM) showed no evidence for a genetic bottleneck. We take a more conservative approach to the interpretation of these results by accepting the evidence of a recent bottleneck. We suggest maintaining the current level of bottlenose dolphin protection in the area and careful monitoring of the population in the future.

Migratory bottlenecks concentrate individuals and populations of Nearctic–Neotropical migrants from across vast breeding areas. The extent to which such concentrations occur has important ramifications for interpreting migratory connectivity and for the vulnerability of populations throughout the annual cycle but investigations of such phenomena are rare. We inferred breeding origins of 11 species of Nearctic–Neotropical migrants captured during fall migration in the Darién region, northwestern Colombia, using feather stable-hydrogen isotope values (δ 2Hf). Our objectives were to determine (1) the extent to which this region acts as a catchment for individuals from across a species’ breeding range, (2) if temporal patterns of arrival arise as a function of migration distance inferred from δ 2Hf, and (3) if phenological differences among species segregate populations. The Darién concentrated populations of 6 species, with individuals potentially derived from 78% to 94% of their respective North American breeding ranges. The catchment area for the remaining 5 species covered 40–72% of breeding ranges, with a bias in origin from the west (e.g., Northern Waterthrush [Parkesia noveboracensis], Swainson’s Thrush [Catharus ustulatus]), north or center (Yellow Warbler [Setophaga petechia]) of their range. Differential timing in the migration of populations occurred in 6 species, generating a degree of temporal segregation. In contrast, peak migration for all species occurred in October, resulting in high overlap among species in their use of the Darién. Overall, our results describe high mixing of populations in the Darién for several species, which, given the region’s highly restricted geographic extent, suggests that a bottleneck effect occurs; however, comparisons with other regions in Central America and northern South America are required. The combination of extensive population mixing and limited temporal segregation over a narrow geographical area suggests that long-distance migrants may be especially vulnerable to events occurring in such regions, including adverse weather conditions and anthropogenic land cover change.

A fire-mediated recruitment bottleneck provides a possible explanation for the coexistence of trees and grasses in mesic savannas. The key element of this hypothesis is that saplings are particularly vulnerable to fire because they are small enough to be top-killed by grass fires, but unlike juveniles, they take several years to recover their original size. This limits the number of recruits into the adult size classes. Thus savanna vegetation may be maintained by a feedback whereby fire restricts the density of adult trees and allows a grass layer to develop, which provides fuel for subsequent fires. Here, we use results from a landscape-scale fire experiment in tropical Australia, to explore the possible existence of a recruitment bottleneck. This experiment compared tree recruitment and survival over 4 y under regimes of no fire, annual early and annual late dry-season fire. Stem mortality decreased with increasing stem height in the fire treatments but not in the unburnt treatment. Tree recruitment was 76–84% lower in the fire treatments than the unburnt treatment. Such fire-induced stem loss of saplings and reduced recruitment to the canopy layer in this eucalypt savanna are consistent with the predictions of the fire-mediated recruitment bottleneck hypothesis.

Census of migrating raptors at Breginjski Stol (NW Slovenia) - the first confirmed bottleneck site in Slovenia From 4 to 31 May 2010, raptor migration was monitored daily between 9.00 and 17.00 hrs CET at Breginjski Stol (NW Slovenia). In all, 2,385 raptor passes were counted, belonging to at least 17 species that were divided into resident and migratory birds. Residents (n = 875 passes) foraged, bred or daily migrated over the area. Among them, Griffon Vulture Gyps fulvus was the most frequent species (n = 575 passes) with the largest observed group of 35 individuals on 26 May. In the morning, Griffon Vultures were flying from west to east in search of food, whereas in the afternoon they were returning in the opposite direction to their colony in Forgaria nel Friuli (Italy). Their numbers increased after 15 May, when Croatian Griffons joined those from Italy. Altogether, 1,510 individuals of migratory raptors were counted, belonging to at least nine species. Among them, Honey Buzzard Pernis apivorus was the most common (1,368 ind., 90.6% of migratory raptors). The migration peak was reached on 14 May, with 552 individuals. Most raptors were seen migrating solitarily or in small flocks (2-4 ind.), whereas on five days (4, 7, 11, 13, 14 May) over 20% of all observed flocks were either medium-sized (5-15 ind.) or large (> 15 ind.). Raptors mostly migrated between 9.00 and 13.00 hrs. Taking into consideration several factors - short observation period and limited number of observation hours per day, overlooked raptors due to human- and topography-related causes, movements of observers between observation points, extremely bad weather and night migration of raptors - we estimate that the actual number of migratory raptors that passed Breginjski Stol in spring 2010 was 3,060-4,660 individuals. Thus, Breginjski Stol is the first confirmed bottleneck site of European importance for migratory raptors in Slovenia, as defined by BirdLife International IBA criterion B1iv, and a natural continuation of migratory pathways from northern Italy.

The Tibetan antelope (chiru, Pantholops hodgsoni) is one of the most endangered mammals native to the Qinghai-Tibetan Plateau. The population size has rapidly declined over the last century due to illegal hunting and habitat damage. In the past 10 years, the population has reportedly been expanding due to conservation efforts. Several lines of evidence suggest that the Tibetan antelope has undergone a demographic bottleneck. However, the consequences of the bottleneck on genetic diversity and the post-bottleneck genetic recovery remain unknown. In this study, we investigate the genetic variation of 15 microsatellite loci from two Tibetan antelope populations sampled in 2003 (Pop2003) and 2013 (Pop2013). A higher level of genetic diversity (NA, 13.286; He, 0.840; PIC, 0.813; I, 2.114) was detected in Pop2013, compared to Pop2003 (NA, 12.929; He, 0.818; PIC, 0.789; I, 2.033). We observe that despite passing through the bottleneck, the Tibetan antelope retains high levels of genetic diversity. Furthermore, our results show significant or near significant increases in genetic diversity (He, PIC and I) in Pop2013 compared with Pop2003, which suggests that protection efforts did not arrive too late for the Tibetan antelope.

Made available in DSpace on 2018-12-11T17:30:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-01-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Issues on the correlation of viral genetic diversity and treatment response to the hepatitis C infection remain uncertain. The bottleneck effect dictates the characteristics of the viral population that will establish the infection in a new host and is related to how the immune system and treatment will be effective against the virus. Here we evaluated the phylogenetic characteristics of quasispecies population and the treatment response pattern of a HCV infected couple. We also analyzed whether the viral population of these patients indicated that they were exposed to the same source for primer infection. This study included two patients (P10 and P11) HCV genotype 1b infected. The couple presented horizontal transmission. Viral RNA was isolated from serum samples collected before, during and after treatment, at specific time points. The HCV NS5A gene sequence was amplified, cloned and sequenced. Genetic and evolutionary analyses were performed to compare the quasispecies population of these two patients and local control patients. Genetic distance and diversity were calculated. Phylogenetic analyses were performed by using maximum likelihood and Bayesian methodologies. The analysis of the baseline samples showed that the genetic distance of the viral populations of patients P10 and P11 was significantly lower than when these patients and the control group based on sequences from local patients were analyzed, supporting the horizontal transmission hypothesis. Phylogenetic analysis with sequences from all the time point samples also demonstrated two patterns of evolution depending on the treatment response. The Bayesian analysis showed that one isolate corresponding to the baseline sample of P10 was grouped into the P11 clade, suggesting a way of infection and a bottleneck effect. Our data suggests that the patient P11 viral population may be originated from variants from P10 patient and consequently showing that clinical differences between treatment responses can emerge from the bottleneck effect on viral populations. Laboratório de Hepatologia Molecular Aplicada LHEMA Disciplina de Gastroenterologia Departamento de Medicina Universidade Federal de São Paulo, Av. Pedro de Toledo n° 669, 5° Andar Laboratório de Parasitologia Instituto Butantan, Av. Vital Brazil, n° 1500 Laboratório de Estudos Genômicos Ibilce UNESP Laboratório de Virologia Instituto de Ciências Biomédicas Universidade Federal de Uberlândia — UFU Laboratório de Estudos Genômicos Ibilce UNESP FAPESP: 2007/52073-0 FAPESP: 2008/51165-1 FAPESP: 2010/06156-4 FAPESP: 2012/18168-2

The prerequisites and ingredients for life seem to be abundantly available in the Universe. However, the Universe does not seem to be teeming with life. The most common explanation for this is a low probability for the emergence of life (an emergence bottleneck), notionally due to the intricacies of the molecular recipe. Here, we present an alternative Gaian bottleneck explanation: If life emerges on a planet, it only rarely evolves quickly enough to regulate greenhouse gases and albedo, thereby maintaining surface temperatures compatible with liquid water and habitability. Such a Gaian bottleneck suggests that (i) extinction is the cosmic default for most life that has ever emerged on the surfaces of wet rocky planets in the Universe and (ii) rocky planets need to be inhabited to remain habitable. In the Gaian bottleneck model, the maintenance of planetary habitability is a property more associated with an unusually rapid evolution of biological regulation of surface volatiles than with the luminosity and distance to the host star.

It is commonly thought that human genetic diversity in non-African populations was primarily shaped by a recent out-of-Africa dispersal. Here we present a large geographical Y chromosome study using 459 high coverage sequences, including 302 newly reported here. We date the Y chromosomal Most Recent Common Ancestor (MRCA) in Africa at 254 (95% CI 192- 307) kya and differentiation of African and non-African lineages 52-121 kya. The age estimates for major non-African founder haplogroups cluster closely in a narrow time interval at 47-52 kya, consistent with a rapid initial colonization model of Eurasia and Oceania after the out-of-Africa bottleneck. We find that the highest basal Y chromosome diversity outside Africa has been preserved in South and Southeast Asians while extant Y chromosome diversity in Europe and the Near East stems from a small number of mid-Holocene founders. In contrast to demographic reconstructions based on mtDNA, we infer a second strong bottleneck, followed by a fast recovery in Old World populations dating to the last 10 ky. We hypothesize that this bottleneck is caused by cultural changes affecting variance of reproductive success among males.

Spatial and environmental heterogeneity are major factors in structuring species distributions in alpine landscapes. These landscapes have also been affected by glacial advances and retreats, causing alpine taxa to undergo range shifts and demographic changes. These nonequilibrium population dynamics have the potential to obscure the effects of environmental factors on the distribution of genetic variation. Here, we investigate how demographic change and environmental factors influence genetic variation in the alpine butterfly Colias behrii. Data from 14 microsatellite loci provide evidence of bottlenecks in all population samples. We test several alternative models of demography using approximate Bayesian computation (ABC), with the results favouring a model in which a recent bottleneck precedes rapid population growth. Applying independent calibrations to microsatellite loci and a nuclear gene, we estimate that this bottleneck affected both northern and southern populations 531-281 years ago, coinciding with a period of global cooling. Using regression approaches, we attempt to separate the effects of population structure, geographical distance and landscape on patterns of population genetic differentiation. Only 40% of the variation in F(ST) is explained by these models, with geographical distance and least-cost distance among meadow patches selected as the best predictors. Various measures of genetic diversity within populations are also decoupled from estimates of local abundance and habitat patch characteristics. Our results demonstrate that demographic change can have a disproportionate influence on genetic diversity in alpine species, contrasting with other studies that suggest landscape features control contemporary demographic processes in high-elevation environments.

Sharp-tailed grouse (Tympanuchus phasianellus) are an area-sensitive species that relies on open landscapes of grass and brush. These areas have become highly fragmented in the Great Lakes Region by succession to forest, agriculture, and other human land uses. We used microsatellites in a landscape-genetic approach to identify landscape features that influence movement and connectivity for sharp-tailed grouse in Minnesota, where they have a regional stronghold. Feathers from leks and hunter wing submissions resulted in 367 individuals from the northwest (NW) and 84 from the east-central (EC) management regions. Both the NW and EC regions were genetically diverse and distinct, with high connectivity between them, although it is unclear whether this connection is contemporary or historical. Our analysis indicated that sharp-tailed grouse were structured across regions by land cover or by the amount of agriculture, grasslands, shrublands, and wet meadows on the larger landscape. Numerous long distance dispersal events were detected. Population clustering analysis indicated greatest support for two genetic clusters in the NW and three clusters in the EC region; however, mapping sample locations of individuals by assigned cluster revealed panmixia of clusters in the EC region. High genetic diversity, a low inbreeding coefficient, and significant excess in heterozygosity are consistent with a recent demographic compression or bottleneck in the EC region, and also consistent with surveys indicating a recent decline there. Sustained low population size or further declines would be expected to reduce genetic diversity. We recommend increasing grassland and shrubland quantity and quality to increase population size in the EC region soon.

A perceived consequence of a population bottleneck is the erosion of genetic diversity and concomitant reduction in individual fitness and evolutionary potential. Although reduced genetic variation associated with demographic perturbation has been amply demonstrated for neutral molecular markers, the effective management of genetic resources in natural populations is hindered by a lack of understanding of how adaptive genetic variation will respond to population fluctuations, given these are affected by selection as well as drift. Here, we demonstrate that selection counters drift to maintain polymorphism at a major histocompatibility complex (MHC) locus through a population bottleneck in an inbred island population of water voles. Before and after the bottleneck, MHC allele frequencies were close to balancing selection equilibrium but became skewed by drift when the population size was critically low. MHC heterozygosity generally conformed to Hardy-Weinberg expectations except in one generation during the population recovery where there was a significant excess of heterozygous genotypes, which simulations ascribed to strong differential MHC-dependent survival. Low allelic diversity and highly skewed frequency distributions at microsatellite loci indicated potent genetic drift due to a strong founder affect and/or previous population bottlenecks. This study is a real-time examination of the predictions of fundamental evolutionary theory in low genetic diversity situations. The findings highlight that conservation efforts to maintain the genetic health and evolutionary potential of natural populations should consider the genetic basis for fitness-related traits, and how such adaptive genetic diversity will vary in response to both the demographic fluctuations and the effects of selection.

Objectives For both HIV-1 and hepatitis C virus (HCV), assessing the stringency of the transmission process is a scientific priority. Enumerations of transmitted/founder (TF) viruses have shown a strict transmission bottleneck in sexual transmission of HIV-1 and a wide range in the multiplicity of infection in HCV. Here, we aim to determine the stringency of parenteral transmission for HIV-1 and HCV in people who inject drugs (PWID). Design We used molecular sequencing and several complementary analyses to enumerate the TF HIV-1 and HCV variants in a well described cohort of PWID in Xinjiang, China. Methods We performed single genome sequencing of HIV-1 env and 5' half HCV genomes, then applied phylogenetic analysis and validated models of early virus diversification to enumerate TF viruses in 60 PWID. We used multivariate analysis to determine correlates of multivariant transmission (MVT). Results We generated 1070 env region sequences from 33 HIV-1 early infected individuals and 773 5' half region sequences from 27 HCV early infected individuals. We found rates of MVT of 39 and 54%, respectively, for HIV-1 and HCV, with a limited range in the number of TF viruses in both infections. Behavioural characteristics suggested high-risk injection practices and lower risk sexual practices; we did not find an association between any specific behaviours and MVT. Conclusion MVT is frequent in parenteral transmission of both HIV-1 and HCV in Xinjiang PWID, indicating a less stringent transmission process than sexual transmission.

We use a branching process approach to estimate the substitution rate, the rate at which beneficial mutations occur and fix, in populations of lytic viruses whose growth is controlled by periodic population bottlenecks. Our model predicts that substitution rates, and by extension adaptation rates, are profoundly affected by the survival of infected host cells at the bottleneck. In particular, we find that direct transfer (or environmental) bottlenecks, in which some fraction of both free virus and host cells are preserved, are associated with relatively slow adaptation rates for the virus. In contrast, viruses can adapt much more quickly when only free virus is transferred to a new host population, as is typical in an epidemiological setting. Finally, when premature lysis of the host-cell population is induced at the bottleneck, we predict that adaptation rates for the virus will, in general, be faster still. These results hold irrespective of the life-history trait affected by the beneficial mutation. The substitution rates in the presence of environmental bottlenecks are predicted to be as much as an order of magnitude lower than in the other two cases.

Reduced, or bottlenecked, populations are more prone to adverse events. Thus, the detection of genetic bottleneck signatures in wildlife is an important issue for conservation. BOTTLENECK 1.2.02 is a software commonly used for detecting genetic characteristics of past bottlenecks. Here we test the efficiency with which this software detects bottlenecks in two koala populations of known history. The sign test performed well for both populations, particularly under the infinite alleles model for mutation. This suggests this model could be the more realistic for marsupial microsatellites than other mutation models. Under the allele frequency distribution test, the two populations falsely appeared to be at mutation/drift equilibrium. However, this test could detect the bottleneck when only imperfect repeat microsatellites were included in the analysis. We thus recommend further investigation of imperfect repeat microsatellites, which could be more powerful for bottleneck detection. These results underline the cautious approach researchers and conservationists should take when studying the past of unknown populations.

The analysis of molecular data from natural populations has allowed researchers to answer diverse ecological questions that were previously intractable. In particular, ecologists are often interested in the demographic history of populations, information that is rarely available from historical records. Methods have been developed to infer demographic parameters from genomic data, but it is not well understood how inferred parameters compare to true population history or depend on aspects of experimental design. Here we present and evaluate a method of SNP discovery using RNA-sequencing and demographic inference using the program δaδi, which uses a diffusion approximation to the allele frequency spectrum to fit demographic models. We test these methods in a population of the checkerspot butterfly Euphydryas gillettii. This population was intentionally introduced to Gothic, Colorado in 1977 and has since experienced extreme fluctuations including bottlenecks of fewer than 25 adults, as documented by nearly annual field surveys. Using RNA-sequencing of eight individuals from Colorado and eight individuals from a native population in Wyoming, we generate the first genomic resources for this system. While demographic inference is commonly used to examine ancient demography, our study demonstrates that our inexpensive, all-in-one approach to marker discovery and genotyping provides sufficient data to accurately infer the timing of a recent bottleneck. This demographic scenario is relevant for many species of conservation concern, few of which have sequenced genomes. Our results are remarkably insensitive to sample size or number of genomic markers, which has important implications for applying this method to other non-model systems.

Genetic factors such as decreased genetic diversity and increased homozygosity can have detrimental effects on rare species, and may ultimately limit potential adaptation and exacerbate population declines. The Gulf and Atlantic Coastal Plain physiographic region has the second highest level of endemism in the continental USA, but habitat fragmentation and land use changes have resulted in catastrophic population declines for many species. Astragalus michauxii (Fabaceae) is an herbaceous plant endemic to the region that is considered vulnerable to extinction, with populations generally consisting of fewer than 20 individuals. We developed eight polymorphic microsatellites and genotyped 355 individuals from 24 populations. We characterized the population genetic diversity and structure, tested for evidence of past bottlenecks, and identified evidence of contemporary gene flow between populations. The mean ratios of the number of alleles to the allelic range (M ratio) across loci for A. michauxii populations were well below the threshold of 0.68 identified as indicative of a past genetic bottleneck. Genetic diversity estimates were similar across regions and populations, and comparable to other long-lived perennial species. Within-population genetic variation accounted for 92 % of the total genetic variation found in the species. Finally, there is evidence for contemporary gene flow among the populations in North Carolina. Although genetic factors can threaten rare species, maintaining habitats through prescribed burning, in concert with other interventions such as population augmentation or (re)introduction, are likely most critical to the long term survival of A. michauxii.

Fishways designed for salmonids often restrict passage by non-salmonids, and effective tools are needed both to identify passage problems for nontarget species and to inform remediation planning. In this case study, we used migration histories from 2170 radio-tagged adult Pacific lamprey (Entosphenus tridentatus) to identify locations of poor passage (bottlenecks) at a large, multifishway dam. Over 10 years, 49% of tagged lamprey that entered fishways failed to pass the dam. Models accounting for repeated attempts by individual lamprey indicated successful passage strongly depended on attempted passage route. Success also varied with time of fishway entry, water temperature, and lamprey body size. Most failed passage attempts terminated in lower fishway segments, but extensive seasonal shifts in bottleneck locations were detected. Ranking metrics helped prioritize bottlenecks and identified sites where structural or operational modifications should improve lamprey passage. Our integration of spatially intensive monitoring with novel analytical techniques was critical to understanding the complex relationships among fishway features, environmental variation, and lamprey behavior. The prioritization framework can be applied to a wide range of fish passage assessments.

Migrating birds are known to avoid topographical barriers. At these barriers, the local environmental conditions often lead to a high concentration of migrants at certain corridors or points usually referred to as ‘bottlenecks’. The Greater Caucasus and the Caspian Sea are such barriers for migrating birds in south-western Asia. A narrow coastal plain between the Greater Caucasus and the Caspian Sea in Azerbaijan (Besh Barmag bottleneck) provides excellent conditions for studying bird migration of a poorly known region. Here, surveys were carried out in autumn 2011 and spring 2012 to count raptor, passerine and waterbird migration from three different observation points. Data for fixed block of six hours continual observations together with random counting hours have been interpolated by a special calculation to obtain estimated grand totals per species. In total, 278 bird species were recorded, eight of which are red-listed as globally threatened by the IUCN (i.e. Sociable Lapwing Vanellus grega...

When analysing the effects of transport policies it is important to adequately control for heterogeneity: previous studies note that ignoring heterogeneity biases the estimated welfare effects of tolling. This paper examines the effects of tolling, in a bottleneck model, with a continuously distributed value of time. With homogeneous users, first-best public tolling has no effect on prices. With heterogeneity it does: low values of time lose, and high values of time gain. The average congestion externality decreases with the heterogeneity in the value of time. Consequently, the welfare gain of first-best tolling also decreases. The more heterogeneous the value of time is, the lower the relative efficiency of a public pay-lane. This finding contrasts with the previous literature. Earlier studies, using static flow congestion, conclude that the relative efficiency increases with this type of heterogeneity. With more heterogeneity in the value of time, the relative efficiency of a private pay-lane is also lower, while that of a public time-invariant toll is higher. Our results suggest that the welfare gains of different tolling schemes are affected differently by heterogeneity. Further, the impact of heterogeneity on the effects of a policy also depends on the type of congestion considered. © 2010 Elsevier Ltd.

International audience; The paper examines the question of the redistribution of toll revenue as seen in a bottleneck congestion model. Our objective is to analyse the impact of this redistribution on total cost and on modal split between railroad and road. Following Tabuchi's two-mode model (Tabuchi, T., 1993. Bottleneck congestion and modal split. Journal of Urban Economics 34, 414-431.), we integrate a redistribution of toll revenue towards public transport into our study. In this context, we investigate two kinds of road toll regimes: a fine toll and a uniform toll. We will consider two types of railroad fare: when it is set equal to the marginal cost and when it is set equal to average cost. These models allow us to show that toll policy to be more efficient as long as toll revenue is directed towards public transport when the railroad fare is equal to average cost. © 2010 Elsevier Ltd.

Population bottlenecks are ubiquitous in nature, and are an inherent feature of the experimental protocol for many laboratory selection experiments. These bottlenecks can have profound effects on the rate and trajectory of evolution. In particular, there is a trade-off between sampling the population too frequently and imposing infrequent, but more severe, bottlenecks. In this paper we consider the effects of population bottlenecks, assuming a burst-death model for the life history of the organism under study. This model assumes that generation times are exponentially distributed and that at each generation, individuals in the population have a fixed number of offspring. The model also allows for a constant death rate between bottlenecks. We use this model to estimate the optimal bottleneck ratio, that is, the fraction of the population that should be sampled at each bottleneck in order to maximize the probability that beneficial mutations occur and are not lost. We find that the optimal ratio is roughly constant with respect to many of the model parameters, and that sampling about 20% of the population will maximize the rate of adaptation.

The relative importance of genetic, demographic, environmental, and catastrophic processes that maintain population bottlenecks has received little consideration. We evaluate the role of these factors in maintaining the Puerto Rican Parrot (Amazona vittata) in a prolonged bottleneck from 1973 through 2000 despite intensive conservation efforts. We first conduct a risk analysis, then examine evidence for the importance of specific processes maintaining the bottleneck using the multiple competing hypotheses approach, and finally integrate these results through a sensitivity analysis of a demographic model using life-stage simulation analysis (LSA) to determine the relative importance of genetic, demographic, environmental, and catastrophic processes on population growth. Annual population growth has been slow and variable (1.0 ± 5.2 parrots per year, or an average λ = 1.05 ± 0.19) from 16 parrots (1973) to a high of 40–42 birds (1997–1998). A risk analysis based on population prediction intervals (PPI) indi...

A number of recent research studies have focused on theoretical and experimental investigation of a bottleneck in a metabolic reaction network. However, there is no study on how the bottleneck affects the performance of a fermentation process when a product is highly toxic and remarkably influences the growth and death of cells. The present work therefore studies the effect of bottleneck on product concentrations under different product toxicity conditions. A generalized bottleneck model in a fed-batch fermentation is constructed including both the bottleneck and the product influences on cell growth and death. The simulation result reveals that when the toxic product strongly influences the cell growth and death, the final product concentration is hardly changed even if the bottleneck is removed, whereas it is markedly changed by the degree of product toxicity. The performance of an ethanol fermentation process is also discussed as a case example to validate this result. In conclusion, when the product is highly toxic, one cannot expect a significant increase in the final product concentration even if removing the bottleneck; rather, it may be more effective to somehow protect the cells so that they can continuously produce the product.

The Siamese crocodile (Crocodylus siamensis), listed in CITES Appendix I, is considered one of the most critically endangered crocodilians in the world, and the reintroductions of it have been tried. Investigation of genetic variation for Siamese crocodile can help to conserve and improve this endangered species. Fourteen microsatellite loci were developed and twelve polymorphic loci were used to investigate the genetic variation and genetic bottleneck hypothesis on 48 captive individuals sampled in Guangdong Provincial Wildlife Rescue Center in Guangzhou. The allele number of polymorphic markers ranged from 2 to 10 per locus, with the average of 4.357. Observed heterozygosity ranged from 0.063 to 0.649 and expected values ranged from 0.259 to 0.844. The Shannon information index and Polymorphic Information Content showed that most of the loci were highly informative with an overall mean of 0.941 and 0.440, respectively. The bottleneck analysis provided evidence of a significant genetic signature of population decline.

Dynamic logarithmic gains (normalised time-varying sensitivities) or their products with metabolite concentrations, called an instantaneous bottleneck ranking indicator (instantaneous BR indicator), can express the time courses of bottleneck enzyme ranking. The integrated value of the instantaneous BR indicator, called an overall BR indicator, provides a ranking of bottleneck enzymes over the entire reaction period of time. Owing to the property of the logarithmic gains, these BR indicators are allowed to include both positive and negative values and in turn raise several questions on the identification of a bottleneck enzyme. To eliminate these questions, the present work studies the identification of bottleneck enzymes in four ethanol fermentation systems using suspended and immobilised cells at pH 4.5 and 5.5 as case studies. These systems consist of both intracellular reactions without cell growth (intracellular reaction systems) and those with cell growth (cell growth systems). The analyses of the intracellular reaction systems reveal that both the suspended and immobilised cell systems at pH 5.5 are not robust. In the cell growth systems, therefore, the analyses are conducted only for the suspended and immobilised cell models at pH 4.5. The enzyme glyceraldehyde 3-phosphate dehydrogenase (gapd) initially has the largest logarithmic gains under all conditions, whereas the system becomes insensitive to it over time. Interestingly, the instantaneous BR indicator for gapd is negatively large. Also, other indicators change in positive and/or negative regions. To deal with these values of different signs, all the indicators are integrated to obtain and rank the overall BR indicators in the order of the magnitudes of their absolute values. The result shows that the ranking of enzymes are completely identical to that of the final ethanol concentrations obtained by finitely increasing or decreasing the relevant enzyme activities in accordance with the signs of overall BR indicators. This result indicates that the enzymes must be ranked in the order of the magnitudes of their absolute values to determine a bottleneck enzyme. As a result, the analyses of the intracellular reaction systems reveal that the bottleneck enzyme is switched from a membrane-bound glucose transporter enzyme to phosphofructokinase when the cell-retaining condition is changed from suspension to immobilisation. In the cell growth systems, gapd is identified as the most likely bottleneck enzyme, suggesting that the gapd activity must be decreased to increase the ethanol productivity.

Although most natural populations are genetically subdivided, they are often analysed as if they were panmictic units. In particular, signals of past demographic size changes are often inferred from genetic data by assuming that the analysed sample is drawn from a population without any internal subdivision. However, it has been shown that a bottleneck signal can result from the presence of some recent immigrants in a population. It thus appears important to contrast these two alternative scenarios in a model choice procedure to prevent wrong conclusions to be made. We use here an Approximate Bayesian Computation (ABC) approach to infer whether observed patterns of genetic diversity in a given sample are more compatible with it being drawn from a panmictic population having gone through some size change, or from one or several demes belonging to a recent finite island model. Simulations show that we can correctly identify samples drawn from a subdivided population in up to 95% of the cases for a wide range of parameters. We apply our model choice procedure to the case of the chimpanzee (Pan troglodytes) and find conclusive evidence that Western and Eastern chimpanzee samples are drawn from a spatially subdivided population.

Background The process of crop domestication has long been a major area of research to gain insights into the history of human civilization and to understand the process of evolution. Loquat (Eriobotrya japonica Lindl.) is one of the typical subtropical fruit trees, which was domesticated in China at least 2000 years ago. In the present study, we re-sequenced the genome of nine wild loquat accessions collected from wide geographical range and 10 representative cultivated loquat cultivars by using RAD-tag tacit to exploit the molecular footprints of domestication. Results We obtained 26.4 Gb clean sequencing data from 19 loquat accessions, with an average of 32.64 M reads per genotype. We identified more than 80,000 SNPs distributed throughout the loquat genome. The SNP density and numbers were slightly higher in the wild loquat populations than that in the cultivated populations. All cultivars were clustered together by structure, phylogenetic and PCA analyses. Conclusion The modern loquat cultivars have experienced a non-significant genetic bottleneck during domestication, and originated from a single domesticated event. Moreover, our study revealed that Hubei province of China is probably the origin center of cultivated loquat. Electronic supplementary material The online version of this article (doi:10.1186/s12864-017-3738-y) contains supplementary material, which is available to authorized users.

The level of genetic diversity within populations of introduced species has received increasing attention as an important factor influenc- ing their survival and adaptive potential. We exam- ined this issue with the Guatemalan potato tuber moth Tecia solanivora, an agricultural pest which has successfully invaded South America and the Canary Islands within the last 20 years. To analyse changes in T. solanivora genetic diversity, the mitochondrial marker cytochrome b was sequenced from individu- als collected across its known distribution area. High haplotypic diversity was observed in Guatemala, whereas only three haplotypes have been found in Venezuela and a single one in the remaining invaded South American countries and the Canary Islands. Invasive haplotypes were not observed in our samples from Guatemala but are closely related to Guatema- lan haplotypes. These results are consistent with the hypotheses that (i) either a few individuals were introduced into Venezuela leading to a strong initial genetic bottleneck, or selection pressure may have lead to the disparition of all but a reduced number of introduced haplotypes, (ii) a second bottleneck occured between Venezuela and Colombia, and (iii) the invasion of the Canary Islands originated from South America. We further reviewed the recent literature to compare this change in genetic diversity with those reported for other invasive species. We quantified the changes in genetic diversity between native and introduced ranges for 57 biological invasions. We found that the genetic homogenization in T. solanivora was among the strongest reported and discuss factors that can explain the success of invasive populations with low genetic diversity.

SummaryPeople simply cannot do two things at once, as shown by research on the so-called psychological refractory period. A new neuroimaging study has now localized the response-selection bottleneck underlying the psychological refractory period to a frontoparietal network.

Dangerous damage to mitochondrial DNA (mtDNA) can be ameliorated during mammalian development through a highly debated mechanism called the mtDNA bottleneck. Uncertainty surrounding this process limits our ability to address inherited mtDNA diseases. We produce a new, physically motivated, generalisable theoretical model for mtDNA populations during development, allowing the first statistical comparison of proposed bottleneck mechanisms. Using approximate Bayesian computation and mouse data, we find most statistical support for a combination of binomial partitioning of mtDNAs at cell divisions and random mtDNA turnover, meaning that the debated exact magnitude of mtDNA copy number depletion is flexible. New experimental measurements from a wild-derived mtDNA pairing in mice confirm the theoretical predictions of this model. We analytically solve a mathematical description of this mechanism, computing probabilities of mtDNA disease onset, efficacy of clinical sampling strategies, and effects of potential dynamic interventions, thus developing a quantitative and experimentally-supported stochastic theory of the bottleneck. DOI: http://dx.doi.org/10.7554/eLife.07464.001, eLife digest Mitochondria are structures that provide vital sources of energy in our cells. DNA contained within mitochondria encodes important mitochondrial machinery, and most human cells contain hundreds or thousands of mitochondrial DNA molecules in addition to the DNA that is stored in the nucleus. Mitochondrial DNA is inherited from mothers via the egg, and the details of this inheritance are poorly understood. This question is important because inherited mistakes in mitochondrial DNA can have detrimental consequences on health, with links to fatal diseases and many other conditions. An unfertilised egg cell contains many copies of mitochondrial DNA molecules; some may have mutations and some may not. After fertilisation, the egg divides, the number of cells in the developing embryo increases, and the number of mitochondrial DNA molecules per cell changes. If the original egg cell contained defective mitochondrial DNA, some of these new cells end up containing more defective copies than others, leading to cell-to-cell differences in the developing embryo. This potentially allows cells with the greatest number of defective mitochondria to be eliminated. The increase in this cell-to-cell variability is called ‘bottlenecking’, and its mechanism remains highly debated. Johnston et al. have now used tools from maths, statistics and new experiments to address this debate, in the light of several studies that measured the mitochondrial DNA content in developing mice. This approach allowed a new theoretical model of mitochondrial DNA during the growth of an organism to be produced, which encompasses a wide range of existing theories and allows them to be compared. This model starts from the viewpoint that the hundreds or thousands of mitochondrial DNA molecules in a cell can be thought of as a population undergoing random ‘birth’ and ‘death’, and it allows the first statistical comparison of the many proposed bottleneck mechanisms. Johnston et al. find support for two ways that cells segregate mitochondria as they multiply, and show that the decrease in the number of mitochondrial DNA molecules during bottlenecking is flexible. This reconciles a debate amongst previous studies. These findings are confirmed using new experimental data from mice, which are genetically distinct from existing studies, illustrating the generality of the model's findings. Furthermore, an analytic mathematical description that describes in detail how bottlenecking might work is produced. Finally, Johnston et al. provide examples using this new theoretical model to suggest therapeutic strategies for diseases caused by mitochondrial DNA mutations. Future work will need to test these suggestions, and link mathematical understanding of mitochondria with healthcare data. DOI: http://dx.doi.org/10.7554/eLife.07464.002

Zooarchaeological analyses have suggested a possible case of late Holocene resource depression in California tule elk (Cervus elaphus nannodes). We develop and conduct a preliminary independent test of this here based on trends in genetic diversity derived from ancient DNA extracted from archaeological elk bone. Mitochondrial DNA sequence data from 24 tule elk temporally dispersed across the late Holocene deposits of the Emeryville Shellmound, California, provide provisional support for a decline in genetic diversity and a population bottleneck beginning about 1600 B.P. Final confirmation of this pattern must await complete replication of the sequences. Stable isotope analyses of the elk bone provide a record of change in the terrestrial environment across the period of deposition and no suggestion that climate change may have played a role in an elk population decline. The analysis has implications for our understanding of change in human behavior and biology during late Holocene of central California, the methodology of resource depression analyses, and the conservation biology of tule elk.

Most vertebrate groups exhibit eye shapes that vary predictably with activity pattern. Nocturnal vertebrates typically have large corneas relative to eye size as an adaptation for increased visual sensitivity. Conversely, diurnal vertebrates generally demonstrate smaller corneas relative to eye size as an adaptation for increased visual acuity. By contrast, several studies have concluded that many mammals exhibit typical nocturnal eye shapes, regardless of activity pattern. However, a recent study has argued that new statistical methods allow eye shape to accurately predict activity patterns of mammals, including cathemeral species (animals that are equally likely to be awake and active at any time of day or night). Here, we conduct a detailed analysis of eye shape and activity pattern in mammals, using a broad comparative sample of 266 species. We find that the eye shapes of cathemeral mammals completely overlap with nocturnal and diurnal species. Additionally, most diurnal and cathemeral mammals have eye shapes that are most similar to those of nocturnal birds and lizards. The only mammalian clade that diverges from this pattern is anthropoids, which have convergently evolved eye shapes similar to those of diurnal birds and lizards. Our results provide additional evidence for a nocturnal ‘bottleneck’ in the early evolution of crown mammals.

The effective number of breedable individuals is a crucial determinant for maintaining genetic variability within a population. The population of Bargur, the hill cattle of South India, has gone down drastically by more than 93 % in the past three decades, and only a few thousand animals are available at present. The present study was undertaken to evaluate Bargur cattle for mutation drift equilibrium and to detect the occurrence of recent genetic bottleneck event, if any, in this population. About 50 unrelated animals, true to the type, were sampled and genotyped at 25 microsatellite loci. The mean observed heterozygosity (0.808±0.023) was higher than the mean expected heterozygosity (0.762±0.008) with 15 out of 25 microsatellite loci exhibiting heterozygosity excess when assumed under Hardy-Weinberg equilibrium. To evaluate Bargur cattle for mutation drift equilibrium, three tests were performed under three different mutation models, viz., infinite allele model (IAM), stepwise mutation model (SMM) and two-phase model (TPM). The observed gene diversity (He) and expected equilibrium gene diversity (Heq) were estimated under different models of microsatellite evo- lution. All the 25 loci were found to exhibit gene diversity excess under IAM and TPM, while 22 loci were having gene diversity excess under SMM. All the three statistical tests, viz., sign test, standardized differences test, and Wilcoxon sign rank test, revealed significant (P

The adoption of self-fertilization from an ancestral outcrossing state is one of the most common evolutionary transitions in the flowering plants. In the mustard family, outcrossing is typically enforced by sporophytic self-incompatibility (SI), but there are also many self-compatible species. The genus Leavenworthia contains taxa that either possess or lack SI. Here, we present data showing that SI is associated with strict outcrossing and that there is widespread trans-specific sequence polymorphism at the locus involved in the recognition of self-pollen (the S-locus). This ancestral polymorphism is consistent with the presence of an outcrossing mating system in the common ancestor of Leavenworthia species, and suggests that there have been several independent losses of SI in the group. When compared with other mustard species, the bulk of Leavenworthia S-allele sequences are highly diverged from those found in other Brassicaceae and show relatively low levels of nucleotide diversity, a pattern that suggests the common ancestor of the genus likely underwent a strong population bottleneck. The hypothesis of postbottleneck S-locus rediversification is supported by tests showing stronger positive selection acting on S-alleles from Leavenworthia than those found in other Brassicaceae.

Although oncogenic mutations predispose tissue stem cells to tumor initiation, the rate-limiting processes for stem cell immortalization remain unknown. In this issue of Cell, Bonnay et al. identify enhanced electron transport chain activity as a critical determinant of this process, establishing metabolic reprogramming as limiting for tumor initiation.

The population of elk (Cervus elaphus roosevelti) inhabiting Afognak Island, Alaska, USA arose from an introduction of 8 individuals from an established population in Washington, USA in 1929, and recently peaked at approximately 1,400 individuals. We examined indices of diversity for 15 microsatellite loci in the Afognak population and compared them to levels in the parent population to determine effects of translocation and demography on genetic variation. The Afognak population differed significantly (P < 0.0001) from the source population in both allele and genotype frequencies. Allelic richness, number of private alleles and multilocus heterozygosity, but not percent loci polymorphic, were significantly lower in Afognak elk. Mean inbreeding coefficients within Afognak (f = 0.019) and source (f = −0.006) populations did not differ significantly from zero. Despite the demographic bottleneck, no evidence of a genetic bottleneck in the Afognak population was detected using a test for heterozygosity excess or mode shift of allele frequencies. Simulations indicated that rapid population growth after the translocation resulted in heterozygosity excess for only 8 years. Conversely, a statistic testing for a bottleneck signature in the ratio of allele number to allele size range (M-ratio) was significant for both the Afognak and source populations, suggesting that the Afognak population had effectively undergone serial bottlenecks. Nonetheless, Afognak failed to show a smaller M-ratio than the parent population, suggesting a failure of that statistic to detect the bottleneck associated with introduction. We show that a severe bottleneck followed by rapid population growth may be undetectable using available tests.

The present study was undertaken to evaluate different Indian riverine buffalo breeds (Bubalus bubalis) for mutation drift equilibrium and occurrence of any recent genetic bottleneck. A total of 330 animals from seven different breeds were analyzed with a set of 24 heterologous microsatellite markers. Three different tests revealed significant heterozygosity excess in all the seven buffalo breeds studied when assumed under infinite alleles model of microsatellite evolution, while it was the reverse with no significant heterozygosity excess when assumed under conservative stepwise mutation model. Under the two-phase model, all the buffalo breeds except Mehsana were found to be in mutation drift equilibrium when evaluated by all the three statistical methods. Standardized differences test and Wilcoxon signed-rank test revealed significant heterozygosity excess suggesting possible cryptic demographic bottleneck in Mehsana buffaloes of Western India.

The slow down in the drug discovery pipeline is, in part, owing to a lack of structural and functional information available for new drug targets. Membrane proteins, the targets of well over 50% of marketed pharmaceuticals, present a particular challenge. As they are not naturally abundant, they must be produced recombinantly for the structural biology that is a prerequisite to structure-based drug design. Unfortunately, however, obtaining high yields of functional, recombinant membrane proteins remains a major bottleneck in contemporary bioscience. While repeated rounds of trial-and-error optimization have not (and cannot) reveal mechanistic details of the biology of recombinant protein production, examination of the host response has provided new insights. To this end, we published an early transcriptome analysis that identified genes implicated in high-yielding yeast cell factories, which has enabled the engineering of improved production strains. These advances offer hope that the bottleneck of membrane protein production can be relieved rationally.

The invention of agriculture (IOA) by anatomically modern humans (AMH) around 10,000 years before present (ybp) is known to have led to an increase in AMH’s carrying capacity and hence its population size. Reconstruction of historical demography using high coverage (~30X) whole genome sequences (WGS) from >700 individuals from different South Asian (SAS) and Southeast Asian (SEA) populations reveals that although several present day populous groups did indeed experience a positive Neolithic Demographic Transition (NDT), most hunter-gatherers (HGs) experienced a demographic decrease. Differential fertility between HGs and non-HGs, exposure of HGs to novel pathogens from non-HGs could have resulted in such contrasting patterns. However, we think the most parsimonious explanation of the drastic decrease in population size of HGs is their displacement/enslavement by non-HGs.Significance StatementThe invention of agriculture, around 10000 years ago, facilitated more food production which could feed larger populations. This had far-reaching socio-political and demographic impacts, including a ~10,000 fold increase in global population-size in the last 10,000 years. However, this increase in population size is not a universal truth and present day hunter-gatherer populations, in contrast, have dwindled in size, often drastically. The signatures of this rise in population size are discernible from the genomes of present-day individuals. Using genomic data, we show that for the majority of Asian hunter-gatherers, population-sizes drastically decreased following the invention of agriculture. We argue that a combination of displacement, enslavement and disease resulted in the decimation of hunter-gatherer societies.