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Population bottlenecks can reduce genetic diversity and may lead to inbreeding depression. However, some studies have provided evidence that long lifespans buffer negative genetic effects of bottlenecks. Others have cautioned that longevity might merely mask the effects of genetic drift, which will still affect long-term population viability. We used microsatellite data from actual populations of tuatara (Sphenodon punctatus) and eastern massasaugas (Sistrurus catenatus) as a starting point for simulated population declines to evaluate the performance of bottleneck tests under a range of scenarios. We quantified losses in genetic diversity for each scenario and assessed the power of commonly used tests (i.e., M-ratio, heterozygosity excess, and mode-shift) to detect known bottlenecks in these moderate- to long-lived species. Declines in genetic diversity were greater in bottlenecks simulated for eastern massasaugas, the shorter-lived species, and mode-shift and heterozygosity excess tests were more sensitive to population declines in this species. Conversely, M-ratio tests were more sensitive to bottlenecks simulated in tuatara. Despite dramatic simulated population declines, heterozygosity excess and mode-shift tests often failed to detect bottlenecks in both species, even when large losses in genetic diversity had occurred (both allelic diversity and heterozygosity). While not eliminating type II error, M-ratio tests generally performed best and were most reliable when a critical value (Mc) of 0.68 was used. However, in tuatara simulations, M-ratio tests had high rates of type I error when Mc was calculated assuming θ = 10. Our results suggest that reliance on these tests could lead to misguided species management decisions.

Mitochondrial DNA (mtDNA) is present in multiple copies within an organism. Since these copies are not identical, a single individual carries a heterogeneous population of mtDNAs, a condition known as heteroplasmy. Several factors play a role in the dynamics of the within-organism mtDNA population: among them, genetic bottlenecks, selection, and strictly maternal inheritance are known to shape the levels of heteroplasmy across mtDNAs. In Metazoa, the only evolutionarily stable exception to the strictly maternal inheritance of mitochondria is the doubly uniparental inheritance (DUI), reported in 100+ bivalve species. In DUI species, there are two highly divergent mtDNA lineages, one inherited through oocyte mitochondria (F-type) and the other through sperm mitochondria (M-type). Having both parents contributing to the mtDNA pool of the progeny makes DUI a unique system to study the dynamics of mtDNA populations. Since, in bivalves, the spermatozoon has few mitochondria (4–5), M-type mtDNA faces a tight bottleneck during embryo segregation, one of the narrowest mitochondrial bottlenecks investigated so far. Here, we analyzed the F- and M-type mtDNA variability within individuals of the DUI species Ruditapes philippinarum and investigated for the first time the effects of such a narrow bottleneck affecting mtDNA populations. As a potential consequence of this narrow bottleneck, the M-type mtDNA shows a large variability in different tissues, a condition so pronounced that it leads to genotypes from different tissues of the same individual not to cluster together. We believe that such results may help understanding the effect of low population size on mtDNA bottleneck.

Critically endangered species that have undergone severe population bottlenecks often have little remaining genetic variation, making it difficult to reconstruct population histories to apply in reintroduction and recovery strategies. By using ancient DNA techniques, it is possible to combine genetic evidence from the historical population with contemporary samples to provide a more complete picture of a species' genetic variation across its historical range and through time. Applying this approach, we examined changes in the mitochondrial DNA (mtDNA) control region (526 base pairs) of the endangered California Condor (Gymnogyps californianus). Results showed a >80% reduction in unique haplotypes over the past 2 centuries. We found no spatial sorting of haplotypes in the historical population; the periphery of the range contained haplotypes that were common throughout the historical range. Direct examination of mtDNA from California Condor museum specimens provided a new window into historical po...

The New Zealand sea lion (NZSL) is of high conservation concern due to its limited distribution and its declining population size. Historically, it occupied most of coastal New Zealand, but is now restricted to a few coastal sites in southern mainland New Zealand and the sub-Antarctic Islands. NZSLs have experienced a recent reduction in population size due to sealing in the 1900s, which is expected to have resulted in increased inbreeding and a loss of genetic variation, potentially reducing the evolutionary capacity of the species and negatively impacting on its long-term prospects for survival. We used 17 microsatellite loci, previously shown to have cross-species applications in pinnipeds, to determine locus- and population-specific statistics for 1205 NZSLs from 7 consecutive breeding seasons. We show that the NZSL population has a moderate level of genetic diversity in comparison to other pinnipeds. We provide genetic evidence for a population reduction, likely caused by historical sealing, and a measure of allele sharing/parental relatedness (internal relatedness) that is suggestive of increased inbreeding in pups that died during recent epizootic episodes. We hypothesize that population bottlenecks and nonrandom mating have impacted on the population genetic architecture of NZSLs, affecting its population recovery.

Despite intensive management since the 1970s, recovery of the endangered northwestern Atlantic population of the Roseate Tern (Sterna dougallii dougallii) has not offset low productivity from a female-biased sex ratio, low adult survival, and habitat constriction. Now, >90% of individuals breed at three sites within 200 km from Long Island, NY, to Buzzards Bay, MA (warm-water subregion). To characterize the impact of historical bottlenecks, metapopulation structure, and demographic fluctuations on genetic variation, Roseate Terns from the warm-water (1870s, 1970s, 1997, 2016) and cold-water (Nova Scotia, Canada; 2018) subregions were genotyped at 8–16 microsatellites and 2–3 mitochondrial regions. Diversity declined in the warm-water subregion from the 1870s (expected heterozygosity [HE] = 0.44, allelic richness [AR] = 2.86) and 1970s (HE = 0.53, AR = 3.25) to 1997 (HE = 0.38, AR = 2.58). Genetic signatures of bottlenecks persisted in 1997 (P =

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.

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 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.

The western bean cutworm, Striacosta albicosta (Smith) (Lepidoptera: Noctuidae), is a pest of both corn and dry bean crops. At the beginning of the 21st century, the species began to extend its range out of the Great Plains, eastward through the Corn Belt. This rapid range expansion is remarkable because the species distribution had been stable for at least the previous half century, despite the apparent abundance of suitable habitat (i.e., cornfields) immediately to the east. We hypothesized that if the western bean cutworm had to overcome a stable barrier to movement before starting the current range expansion, it probably experienced a genetic bottleneck in doing so. To test this hypothesis, variation in the mitochondrial NADH dehydrogenase one (ND1) gene was studied in populations from Wyoming, Nebraska, and Iowa. No differences in overall genetic diversity or haplotype frequencies indicative of a bottleneck were observed between the recently founded populations in Iowa and the established populations in Wyoming and Nebraska. This result suggests that the sudden loss of an ecological exclusion mechanism, allowing the species to move east in appreciable numbers, is more likely to have triggered the range expansion than the surmounting of an extrinsic barrier to movement. The nature of this mechanism is unknown but might be related to recent changes in corn farming practices and technology.

Multilocus surveys of sequence variation can be used to identify targets of directional selection, which are expected to have reduced levels of variation. Following a population bottleneck, the signal of directional selection may be hard to detect because many loci may have low variation by chance and the frequency spectrum of variation may be perturbed in ways that resemble the effects of selection. Cultivated Sorghum bicolor contains a subset of the genetic diversity found in its wild ancestor(s) due to the combined effects of a domestication bottleneck and human selection on traits associated with agriculture. As a framework for distinguishing between the effects of demography and selection, we sequenced 204 loci in a diverse panel of 17 cultivated S. bicolor accessions. Genomewide patterns of diversity depart strongly from equilibrium expectations with regard to the variance of the number of segregating sites, the site frequency spectrum, and haplotype configuration. Furthermore, gene genealogies of most loci with an excess of low frequency variants and/or an excess of segregating sites do not show the characteristic signatures of directional and diversifying selection, respectively. A simple bottleneck model provides an improved but inadequate fit to the data, suggesting the action of other population-level factors, such as population structure and migration. Despite a known history of recent selection, we find little evidence for directional selection, likely due to low statistical power and lack of an appropriate null model.

Grant, W. S., Merkouris, S. E., Kruse, G. H., and Seeb, L. W. 2011. Low allozyme heterozygosity in North Pacific and Bering Sea populations of red king crab (Paralithodes camtschaticus): adaptive specialization, population bottleneck, or metapopulation structure? – ICES Journal of Marine Science, 68: . Populations of red king crab in the North Pacific and Bering Sea have declined in response to ocean-climate shifts and to harvesting. An understanding of how populations are geographically structured is important to the management of these depressed resources. Here, the Mendelian variability at 38 enzyme-encoding loci was surveyed in 27 samples (n = 2427) from 18 general locations. Sample heterozygosities were low, averaging HE = 0.015 among samples. Weak genetic structure was detected among three groups of populations, the Bering Sea, central Gulf of Alaska, and Southeast Alaska, but without significant isolation by distance among populations. A sample from Adak Island in the western Aleutians was genetically different from the remaining samples. The lack of differentiation among populations within regions may, in part, be due to post-glacial expansions and a lack of migration-drift equilibrium and to limited statistical power imposed by low levels of polymorphism. Departures from neutrality may reflect the effects of both selective and historical factors. The low allozyme diversity in red king crab may, in part, be attributable to adaptive specialization, background selection, ice-age population bottlenecks, or metapopulation dynamics in a climatically unstable North Pacific.

The ability of microbial populations to increase fitness through fixation of mutants with an increased growth rate has been well described. In experimental studies, this is often the only way fitness can be increased. In natural settings, however, fitness can also be improved by increasing the ability of the microbe to transmit from one host to the next. For many pathogens, transmission includes a phase outside the host during which they need to survive before the chance of reinfecting a new host occurs. In such a situation, a reduced death rate during this phase will lead to improved fitness. Here, we compute the fixation probability of mutants that better survive the transmission bottleneck during the evolution of microbial populations. We derive analytical results that show that transmission mutants are often likely to occur and that their importance relative to growth mutants increases as the population decline during the transmission phase increases. We confirm our theoretical results with numerical simulations and suggest specific experiments that can be done to test our predictions.

The long-term viability of small, isolated populations has been questioned in light of stochasticity and bottlenecks. Following a drought in northwestern Montana in 2003, the pronghorn (Antilocapra americana )o f the National Bison Range experienced a demographic bottleneck. We used information theoretic approaches to examine the influence of sex, age, genetic variation, summer lactation, mate-search effort by females, and mating effort by males on subsequent winter survival and spring fecundity. Survival of males was influenced by age, whereas survival of females was influenced by prior energy expenditure and genetic variation, implicating inbreeding depression as the mechanism. Fecundity of females also was influenced by prior energy expenditure and genetic variation, with heterosis as the apparent mechanism. Our results agree with those of other studies that have emphasized the need to maintain genetic variation and limit inbreeding in small, isolated populations, and to account for stochasticity in population viability assessments and long-term management planning.

Neisseria meningitidis is the leading cause of epidemic meningitis in the “meningitis belt” of Africa, where clonal waves of colonization and disease are observed. Point mutations and horizontal gene exchange lead to constant diversification of meningococcal populations during clonal spread. Maintaining a high genomic diversity may be an evolutionary strategy of meningococci that increases chances of fixing occasionally new highly successful “fit genotypes”. We have performed a longitudinal study of meningococcal carriage and disease in northern Ghana by analyzing cerebrospinal fluid samples from all suspected meningitis cases and monitoring carriage of meningococci by twice yearly colonization surveys. In the framework of this study, we observed complete replacement of an A: sequence types (ST)-2859 clone by a W: ST-2881 clone. However, after a gap of 1 year, A: ST-2859 meningococci re-emerged both as colonizer and meningitis causing agent. Our whole genome sequencing analyses compared the A population isolated prior to the W colonization and disease wave with the re-emerging A meningococci. This analysis revealed expansion of one clone differing in only one nonsynonymous SNP from several isolates already present in the original A: ST-2859 population. The colonization bottleneck caused by the competing W meningococci thus resulted in a profound reduction in genomic diversity of the A meningococcal population.

The black-footed ferret (Mustela nigripes) is an endangered North American carnivore that underwent a well-documented population bottleneck in the mid-1980s. To better understand the effects of a bottleneck on a free-ranging carnivore population, we used 24 microsatellite loci to compare genetic diversity before versus during the bottleneck, and compare the last wild population to two historical populations. We also compared genetic diversity in black-footed ferrets to that of two sibling species, the steppe polecat (Mustela eversmanni) and the European polecat (Mustela putorius). Black-footed ferrets during the bottleneck had less genetic diversity than steppe polecats. The three black-footed ferret populations were well differentiated (F(ST) = 0.57 +/- 0.15; mean +/- SE). We attributed the decrease in genetic diversity in black-footed ferrets to localized extinction of these genetically distinct subpopulations and to the bottleneck in the surviving subpopulation. Although genetic diversity decreased, female fecundity and juvenile survival were not affected by the population bottleneck.

Associative overdominance, the fitness difference between heterozygotes and homozygotes at a neutral locus, is classically described using two categories of models: linkage disequilibrium in small populations or identity disequilibrium in infinite, partially selfing populations. In both cases, only equilibrium situations have been considered. In the present study, associative overdominance is related to the distribution of individual inbreeding levels (i.e., genomic autozygosity). Our model integrates the effects of physical linkage and variation in inbreeding history among individual pedigrees. Hence, linkage and identity disequilibrium, traditionally presented as alternatives, are summarized within a single framework. This allows studying nonequilibrium situations in which both occur simultaneously. The model is applied to the case of an infinite population undergoing a sustained population bottleneck. The effects of bottleneck size, mating system, marker gene diversity, deleterious genomic mutation parameters, and physical linkage are evaluated. Bottlenecks transiently generate much larger associative overdominance than observed in equilibrium finite populations and represent a plausible explanation of empirical results obtained, for instance, in marine species. Moreover, the main origin of associative overdominance is random variation in individual inbreeding whereas physical linkage has little effect.

Vertebrate color vision has evolved partly through the modification of five ancestral visual opsin proteins via gene duplication, loss, and shifts in spectral sensitivity. While many vertebrates, particularly mammals, birds, and fishes, have had their visual opsin repertoires studied in great detail, testudines (turtles) and crocodylians have largely been neglected. Here I examine the genomic basis for color vision in four species of turtles and four species of crocodylians, and demonstrate that while turtles appear to vary in their number of visual opsins, crocodylians experienced a reduction in their color discrimination capacity after their divergence from Aves. Based on the opsin sequences present in their genomes and previous measurements of crocodylian cones, I provide evidence that crocodylians have co-opted the rod opsin (RH1) for cone function. This suggests that some crocodylians might have reinvented trichromatic color vision in a novel way, analogous to several primate lineages. The loss of visual opsins in crocodylians paralleled the loss of various anatomical features associated with photoreception, attributed to a "nocturnal bottleneck" similar to that hypothesized for Mesozoic mammals. I further queried crocodylian genomes for nonvisual opsins and genes associated with protection from ultraviolet light, and found evidence for gene inactivation or loss for several of these genes. Two genes, encoding parietopsin and parapinopsin, were additionally inactivated in birds and turtles, likely co-occurring with the loss of the parietal eye in these lineages.

The aim of this work was to gather information about the origin and genetic characterization of the Central European Hucul horse based on 71 horses using 17 microsatellites and the D-loop region of mtDNA. Their genetic relationship to the Polish Konik (N = 7), German (N = 4) and Hungarian wild Przewalski horses (N = 4) and 200 horse sequences from GenBank was also analysed. Both microsatellite and mtDNA analysis showed a high genetic variation in the Hucul. A total of 130 alleles were detected, the mean number of observed alleles per microsatellite was 7.647, and the number of effective alleles was 4.401. The average observed and expected heterozygosity were 0.706 and 0.747, respectively. The high heterozygosity values and Wright's fixation index (FIS) (−0.128) indicated a low level of inbreeding, low or no selection pressure, and large number of alleles. mtDNA analysis revealed 18 haplotypes for the Hucul population with a total of 23 variable sites. Haplotype and nucleotide diversities were 0.935 ± 0.011 and 0.022 ± 0.012, respectively. Neutrality tests (Tajima's D and Fu's Fs) were non-significant, and mismatch distribution was ragged, indicating that the Hucul population is in genetic equilibrium. The most frequent mtDNA D-loop region belonged to haplogroup A (48%), which was also present in Przewalski Wild horse samples, while Polish Konik samples belonged to three haplotypes and C, F, and G haplogroups. Large and significant pairwise ΦST values along with a small number of common haplotypes indicated a low level of gene flow and lack of genetic structure among the three studied breeds (Hucul, Konik, and Przewalski Wild horse). The present work contributes to our knowledge of the genetic diversity of the Hucul horse and helps to define its genetic conservation. © 2013 The Linnean Society of London, Biological Journal of the Linnean Society, 2013, 109, 54–65.

Phylogeographical research has revealed several paradigm patterns of postglacial range expansion from the Mediterranean peninsulas to more northern parts of Europe. These range expansions have consequences for the genetic constitution of populations. Although many studies have been performed in mainland Europe, the colonization history of the British Isles is relatively poorly studied; the genetic consequences of the last glacial readvances and the climate optimum conditions, as well as the implications of the recent climatic conditions on the population genetic structures, are little understood. Therefore, we selected the common blue butterfly Polyommatus icarus as a model species for understanding more generally the colonization patterns of the British Isles and the genetic dynamics on these islands. Allozyme analyses of this butterfly show a rather high genetic diversity over continental Europe without major genetic differentiation. The situation on the British Isles is completely different. Here, populations show a much lower genetic diversity compared to mainland Europe. The genetic constitution is well differentiated from that observed on the European mainland, and the genetic differentiation among populations in Britain is stronger than at the European scale. These results support the hypothesis that a relatively cold-tolerant species such as the common blue could have colonized the British Isles early during the late glacial period and survived the last glacial readvances in small refugia in the South. The retraction of this species in small isolated populations could have caused the genetic impoverishment found. The subsequent forest climax during the climate optimum possibly restricted further expansion of this early succession species to small pockets all over the British Isles, resulting in the genetic patchwork that is still observed. Additionally, the relatively cool and rainy conditions one these islands might have caused bottlenecks, possibly enforcing these genetic patterns.

Varying degrees of reduction of genetic diversity in crops relative to their wild progenitors occurred during the process of domestication. Such information, however, has not been available for the Asian cultivated rice (Oryza sativa) despite its importance as a staple food and a model organism. To reveal levels and patterns of nucleotide diversity and to elucidate the genetic relationship and demographic history of O. sativa and its close relatives (Oryza rufipogon and Oryza nivara), we investigated nucleotide diversity data from 10 unlinked nuclear loci in species-wide samples of these species. The results indicated that O. rufipogon and O. nivara possessed comparable levels of nucleotide variation ((sil) = 0.0077 approximately 0.0095) compared with the relatives of other crops. In contrast, nucleotide diversity of O. sativa was as low as (sil) = 0.0024 and even lower ((sil) = 0.0021 for indica and 0.0011 for japonica), if we consider the 2 subspecies separately. Overall, only 20-10% of the diversity in the wild species was retained in 2 subspecies of the cultivated rice (indica and japonica), respectively. Because statistic tests did not reject the assumption of neutrality for all 10 loci, we further used coalescent to simulate bottlenecks under various lengths and population sizes to better understand the domestication process. Consistent with the dramatic reduction in nucleotide diversity, we detected a severe domestication bottleneck and demonstrated that the sequence diversity currently found in the rice genome could be explained by a founding population of 1,500 individuals if the initial domestication event occurred over a 3,000-year period. Phylogenetic analyses revealed close genetic relationships and ambiguous species boundary of O. rufipogon and O. nivara, providing additional evidence to treat them as 2 ecotypes of a single species. Lowest linkage disequilibrium (LD) was found in the perennial O. rufipogon where the r(2) value dropped to a negligible level within 400 bp, and the highest in the japonica rice where LD extended to the entirely sequenced region ( approximately 900 bp), implying that LD mapping by genome scans may not be feasible in wild rice due to the high density of markers needed.

The process for discovery and development of biomarkers of solid tumors presents exceptional challenges. The major technical obstacle is the disconnection between the site of their generation (tissue, proximal fluid) and the source of detection (body fluids, predominantly serum and plasma). This single factor limits, in practical terms, the potential pool of biomarkers to those that are secreted, shed, or leaked from the cell surface. On reaching the circulation, a biomarker undergoes “dilution” into a mixture of thousands of proteins that are present at concentrations spanning at least 10 orders of magnitude. Furthermore, the integrity of a circulating biomarker may be compromised by proteolytic degradation or distortion of its posttranslational modifications. Other levels of complexity involve the inherent variability of biological systems (intraindividual and across a population) and ambiguities in defining disease phenotypes. Finally, fundamental and technological difficulties involved in biomarker studies are exacerbated by preanalytical variables associated with sample collection, handling, and storage (1, 2). An ideal cancer biomarker would be detectable in body fluids at an early stage of disease in a highly specific and selective fashion and be measurable for an inexpensive price. Development of such a biomarker is not a trivial endeavor. To promote efficiency and rigor in cancer biomarker research, Pepe et al. (3) introduced guidelines for a generally appropriate process that could be applied to many other diseases and classes of biomarker (e.g., a protein or a metabolite). These guidelines propose specific aims and measures of success for each of the 5 phases of a biomarker discovery pipeline in the context of progress being made in the field and relevant published studies. It is now evident that the majority of proteomics and genomics studies published to date do not progress far beyond the discovery stage (phase 1), because the development of clinical …

Selection for increased morphometric shape (ratio of wing length to thorax width) was compared between control (nonbottlenecked) populations and bottlenecked populations founded with two male-female pairs of flies. Contrary to neutral expectation, selectional response was not reduced in bottlenecked populations, and the mean realized heritabilities and additive genetic variances were higher for the bottlenecked lines than for the nonbottlenecked lines. Additive genetic variances based on these realized heritabilities were consistent with independent estimates of genetic variances based on parent-offspring covariances. Joint scaling tests applied to the crosses between selected lines and their controls revealed significant nonadditive components of genetic variance in the ancestor, which were not detected in the crosses involving bottlenecked lines. The nonbottlenecked lines responded principally by changes in one trait or the other (wing length or thorax width) but not in both, and regardless of which trait responded, larger trait size was dominant and epistatic to smaller size. Stabilizing selection for morphometric shape in the ancestor likely molded the genetic architecture to include nonadditive genetic effects.

RICH et al. ([1998][1]) have recently proposed that the current world population of the human malaria parasite Plasmodium falciparum consists of individuals descended from a single haploid genotype or strain (malarial Eve) that occurred between 24,500 and 57,500 years ago. They base this conclusion

Effects of a population bottleneck (founder-flush cycle) upon quantitative genetic variation of morphometric traits were examined in replicated experimental lines of the housefly founded with one, four or 16 pairs of flies. Heritability and additive genetic variances for eight morphometric traits generally increased as a result of the bottleneck, but the pattern of increase among bottleneck sizes differed among traits. Principal axes of the additive genetic correlation matrix for the control line yielded two suites of traits, one associated with general body size and another set largely independent of body size. In the former set containing five of the traits, additive genetic variance was greatest in the bottleneck size of four pairs, whereas in the latter set of two traits the largest additive genetic variance occurred in the smallest bottleneck size of one pair. One trait exhibited changes in additive genetic variance intermediate between these two major responses. These results were inconsistent with models of additive effects of alleles within loci or of additive effects among loci. An observed decline in viability measures and body size in the bottleneck lines also indicated that there was nonadditivity of allelic effects for these traits. Several possible nonadditive models were explored that increased additive genetic variance as a result of a bottleneck. These included a model with complete dominance, a model with overdominance and a model incorporating multiplicative epistasis.

A model is presented in which a large population in mutation/drift equilibrium undergoes a severe restriction in size and subsequently remains at the small size. The rate of loss of genetic variability has been studied. Allelic loss occurs more rapidly than loss of genic heterozygosity. Rare alleles are lost especially rapidly. The result is a transient deficiency in the total number of alleles observed in samples taken from the reduced population when compared with the number expected in a sample from a steady-state population having the same observed heterozygosity. Alternatively, the population can be considered to posses excess gene diversity if the number of alleles is used as the statistical estimator of mutation rate. The deficit in allele number arises principally from a lack of those alleles that are expected to appear only once or twice in the sample. The magnitude of the allelic deficiency is less, however, than the excess that an earlier study predicted to follow a rapid population expansion. This suggests that populations that have undergone a single bottleneck event, followed by rapid population growth, should have an apparent excess number of alleles, given the observed level of genic heterozygosity and provided that the bottleneck has not occurred very recently. Conversely, such populations will be deficient for observed heterozygosity if allele number is used as the sufficient statistic for the estimation of 4Nev. Populations that have undergone very recent restrictions in size should show the opposite tendencies.

Differentiation in morphometric traits among experimental populations of the housefly subjected to an experimental bottleneck was examined for replicate lines founded with one, four or 16 pairs of flies. Differentiation among lines within a bottleneck size was significantly greater than predicted by drift in relation to the additive genetic variation for these traits within the founding population. Two models of nonadditive genetic variance were investigated to interpret these results, one involving dominance of allelic effects within loci and another incorporating multiplicative epistasis. Both models generated more variation among lines as a direct result of sampling during the bottleneck than predicted by a model with additive gene action. The pattern of differentiation among our experimental lines in relation to these models conformed more to the model incorporating epistasis. Nevertheless, it may be difficult to distinguish differentiation among lines occurring during a bottleneck as a result of nonadditive gene action from that caused by diversifying selection among lines after the bottleneck.

Multivariate phenotypic differentiation in eight morphometric traits was examined in bottleneck lines of the housefly initiated with one, four, or 16 pairs of flies from a natural outbred population. Differentiation was assessed using a Mahalanobis' distance metric in units of additive genetic variance and covariance estimated from the ancestral population (i.e., generalized genetic distance). This distance metric was partitioned into contributions of size and shape to total distance. Bottleneck lines of all sizes diverged significantly from the ancestral line, but the direction of these shifts differed among the lines of different initial founding size. Those populations founded with single pairs diverged from the ancestral line mostly in shape; the 16-pair lines differentiated almost entirely in size, and the four-pair lines were intermediate in the relative contribution of shape to differentiation from the control. Bottlenecks serve to alter the genetic relationships among traits within the derived populations and in doing so could promote speciation by permitting differentiation of the populations along evolutionary trajectories less accessible to the base population.

Inferring selective sweeps from genetic data has been a breakthrough in population genetics. The most prominent examples come from populations suddenly exposed to extreme stressors, such as insecticides... One of the most useful models in population genetics is that of a selective sweep and the consequent hitch-hiking of linked neutral alleles. While variations on this model typically assume constant population size, many instances of strong selection and rapid adaptation in nature may co-occur with complex demography. Here, we extend the hitch-hiking model to evolutionary rescue, where adaptation and demography not only co-occur but are intimately entwined. Our results show how this feedback between demography and evolution determines—and restricts—the genetic signatures of evolutionary rescue, and how these differ from the signatures of sweeps in populations of constant size. In particular, we find rescue to harden sweeps from standing variance or new mutation (but not from migration), reduce genetic diversity both at the selected site and genome-wide, and increase the range of observed Tajima’s D values. For a given initial rate of population decline, the feedback between demography and evolution makes all of these differences more dramatic under weaker selection, where bottlenecks are prolonged. Nevertheless, it is likely difficult to infer the co-incident timing of the sweep and bottleneck from these simple signatures, never mind a feedback between them. Temporal samples spanning contemporary rescue events may offer one way forward.

Historical specimens in museum collections provide opportunities to gain insights into the genomic past. For the Western honey bee, Apis mellifera L., this is particularly important because its populations are currently under threat worldwide and have experienced many changes in management and environment over the last century. Using Swiss Apis mellifera mellifera as a case study, our research provides important insights into the genetic diversity of native honey bees prior to the industrial-scale introductions and trade of non-native stocks during the 20th century-the onset of intensive commercial breeding and the decline of wild honey bees following the arrival of Varroa destructor. We sequenced whole-genomes of 22 honey bees from the Natural History Museum in Bern collected in Switzerland, including the oldest A. mellifera sample ever sequenced. We identify both, a historic and a recent migrant, natural or human-mediated, which corroborates with the population history of honey bees in Switzerland. Contrary to what we expected, we find no evidence for a significant genetic bottleneck in Swiss honey bees, and find that genetic diversity is not only maintained, but even slightly increased, most probably due to modern apicultural practices. Finally, we identify signals of selection between historic and modern honey bee populations associated with genes enriched in functions linked to xenobiotics, suggesting a possible selective pressure from the increasing use and diversity of chemicals used in agriculture and apiculture over the last century. We are very grateful to Dr Hannes Baur from the Natural History Museum in Bern for giving us access to the historic museum specimens. DNA extractions were performed at SGIker facilities, the genotyping and sequencing platform of the University of the Basque Country, with the special assistance of Dr Irati Miguel and Dr Fernando Rendo. We thank the two anonymous reviewers whose comments and suggestions helped improve this manuscript. Sequencing was performed at the GeT PlaGe platform in Toulouse, France. M.P. was supported by a Postdoc fellowship awarded by the Swiss National Science Foundation (SNSF) (P2BEP3_178489). D.H. was supported by the project BeeHappy (POCI-01-0145-FEDER-029871) funded by FEDER (Fundo Europeu de Desenvolvimento Regional) through the program COMPETE 2020-POCI (Programa Operacional para a Competividade e Internacionalizacao), and by Portuguese funds through FCT (Fundacao para a Ciencia e a Tecnologia).

The Eurasian field vole (Microtus agrestis) comprises three evolutionarily significant units (ESUs). The northern ESU is found at higher latitudes across the western Palaearctic region and includes six, largely allopatric, mitochondrial DNA lineages that were derived from population bottlenecks. One of these lineages is found in southern Britain and nearby areas of continental Europe. A prominent sub-lineage is nested within, and therefore derived from, the part of this lineage occupying southern Britain. The sub-lineage consists of an abundant central haplotype together with a series of closely related haplotypes, a distribution that would result from either a recent population bottleneck or a selective sweep. To distinguish between these, we sequenced a Y-chromosome marker in 167 field voles from Britain and Europe, and analysed a panel of 13 autosomal microsatellite loci in 144 field voles from eight populations in Britain. The Y-chromosome marker showed a continental-scale pattern of variation that was not aligned with that of the mitochondrial marker, while microsatellite variation did not show any evidence for a bottleneck, tentatively favouring selection instead. This implies a role for both stochastic and selective processes in generating phylogeographical patterns at different scales in the field vole.

Motivation Correlating genetic loci with a disease phenotype is a common approach to improve our understanding of the genetics underlying complex diseases. Standard analyses mostly ignore two aspects, namely genetic heterogeneity and interactions between loci. Genetic heterogeneity, the phenomenon that different genetic markers lead to the same phenotype, promises to increase statistical power by aggregating low-signal variants. Incorporating interactions between loci results in a computational and statistical bottleneck due to the vast amount of candidate interactions. Results We propose a novel method SiNIMin that addresses these two aspects by finding pairs of interacting genes that are, upon combination, associated with a phenotype of interest under a model of genetic heterogeneity. We guide the interaction search using biological prior knowledge in the form of protein-protein interaction networks. Our method controls type I error and outperforms state-of-the-art methods with respect to statistical power. Additionally, we find novel associations for multiple A. thaliana phenotypes, and for a study of rare variants in migraine patients. Availability Code available at https://github.com/BorgwardtLab/SiNIMin., Bioinformatics, 37 (1), ISSN:1367-4803, ISSN:1460-2059

Synopsis The class Bivalvia is a highly successful and ancient taxon including ∼25,000 living species. During their long evolutionary history bivalves adapted to a wide range of physicochemical conditions, habitats, biological interactions, and feeding habits. Bivalves can have strikingly different size, and despite their apparently simple body plan, they evolved very different shell shapes, and complex anatomic structures. One of the most striking features of this class of animals is their peculiar mitochondrial biology: some bivalves have facultatively anaerobic mitochondria that allow them to survive prolonged periods of anoxia/hypoxia. Moreover, more than 100 species have now been reported showing the only known evolutionarily stable exception to the strictly maternal inheritance of mitochondria in animals, named doubly uniparental inheritance. Mitochondrial activity is fundamental to eukaryotic life, and thanks to their diversity and uncommon features, bivalves represent a great model system to expand our knowledge about mitochondrial biology, so far limited to a few species. We highlight recent works studying mitochondrial biology in bivalves at either genomic or physiological level. A link between these two approaches is still missing, and we believe that an integrated approach and collaborative relationships are the only possible ways to be successful in such endeavor.

Understanding the patterns of genetic diversity and adaptation across species’ range is crucial to assess its long-term persistence and determine appropriate conservation measures. The impacts of human activities on the genetic diversity and genetic adaptation to heterogeneous environments remain poorly understood in the marine realm. The roughskin sculpin (Trachidermus fasciatus) is a small catadromous fish, and has been listed as a second-class state protected aquatic animal since 1988 in China. To elucidate the underlying mechanism of population genetic structuring and genetic adaptations to local environments, RAD tags were sequenced for 202 individuals in nine populations across the range of T. fasciatus in China. The pairwise FST values over 9,271 filtered SNPs were significant except that between Dongying and Weifang. All the genetic clustering analysis revealed significant population structure with high support for eight distinct genetic clusters. Both the minor allele frequency spectra and Ne estimations suggested extremely small Ne in some populations (e.g., Qinhuangdao, Rongcheng, Wendeng, and Qingdao), which might result from recent population bottleneck. The strong genetic structure can be partly attributed to genetic drift and habitat fragmentation, likely due to the anthropogenic activities. Annotations of candidate adaptive loci suggested that genes involved in metabolism, development, and osmoregulation were critical for adaptation to spatially heterogenous environment of local populations. In the context of anthropogenic activities and environmental change, results of the present population genomic work provided important contributions to the understanding of genetic differentiation and adaptation to changing environments.

Gaining a better understanding on how selection and neutral processes affect genomic diversity is essential to gain better insights into the mechanisms driving adaptation and speciation. However, the evolutionary processes affecting variation at a genomic scale have not been investigated in most vertebrate lineages. Here, we present the first population genomics survey using whole genome resequencing in the green anole (Anolis carolinensis). Anoles have been intensively studied to understand mechanisms underlying adaptation and speciation. The green anole in particular is an important model to study genome evolution. We quantified how demography, recombination, and selection have led to the current genetic diversity of the green anole by using whole-genome resequencing of five genetic clusters covering the entire species range. The differentiation of green anole’s populations is consistent with a northward expansion from South Florida followed by genetic isolation and subsequent gene flow among adjacent genetic clusters. Dispersal out-of-Florida was accompanied by a drastic population bottleneck followed by a rapid population expansion. This event was accompanied by male-biased dispersal and/or selective sweeps on the X chromosome. We show that the interaction between linked selection and recombination is the main contributor to the genomic landscape of differentiation in the anole genome.

International audience; Human-driven global environmental changes have considerably increased the risk of biological invasions, especially the spread of human parasites and their vectors. Among exotic species that have major impacts on public health, the dengue fever mosquito Aedes aegypti originating from Africa has spread worldwide during the last three centuries. Although considerable progress has been recently made in understanding the history of this invasion, the respective roles of human and abiotic factors in shaping patterns of genetic diversity remain largely unexplored. Using a genome-wide sample of genetic variants (3,530 ddRAD SNPs), we analyzed the genetic structure of Ae. aegypti populations in the Caribbean, the first introduced territories in the Americas. Fourteen populations were sampled in Guyane and in four islands of the Antilles that differ in climatic conditions, intensity of urbanization, and vector control history. The genetic diversity in the Caribbean was low (He = 0.14-0.17), as compared with a single African collection from Benin (He = 0.26) and site-frequency spectrum analysis detected an ancient bottleneck dating back ∼300 years ago, supporting a founder event during the introduction of Ae. aegypti. Evidence for a more recent bottleneck may be related to the eradication program undertaken on the American continent in the 1950s. Among 12 loci detected as FST-outliers, two were located in candidate genes for insecticide resistance (cytochrome P450 and voltage-gated sodium channel). Genome-environment association tests identified additional loci associated with human density and/or deltamethrin resistance. Our results highlight the high impact of human pressures on the demographic history and genetic variation of Ae. aegypti Caribbean populations.

Migratory birds use numerous strategies to successfully complete twice-annual movements between breeding and wintering sites. Context for conservation and management can be provided by characterizing these strategies. Variations in strategy among and within individuals support population persistence in response to changes in land use and climate. We used location data from 58 marked Whooping Cranes (Grus americana) from 2010 to 2016 to characterize migration strategies in the U.S. Great Plains and Canadian Prairies and southern boreal region, and to explore sources of heterogeneity in their migration strategy, including space use, timing, and performance. Whooping Cranes completed ~3,900-km migrations that averaged 29 days during spring and 45 days during autumn, while making 11–12 nighttime stops. At the scale of our analysis, individual Whooping Cranes showed little consistency in stopover sites used among migration seasons (i.e. low site fidelity). In contrast, individuals expressed a measure of consistency in timing, especially migration initiation dates. Whooping Cranes migrated at different times based on age and reproductive status, where adults with young initiated autumn migration after other birds, and adults with and without young initiated spring migration before subadult birds. Time spent at stopover sites was positively associated with migration bout length and negatively associated with time spent at previous stopover sites, indicating Whooping Cranes acquired energy resources at some stopover sites that they used to fuel migration. Whooping Cranes were faithful to a defined migration corridor but showed less fidelity in their selection of nighttime stopover sites; hence, spatial targeting of conservation actions may be better informed by associations with landscape and habitat features rather than documented past use at specific locations. The preservation of variation in migration strategies existing within this species that experienced a severe population bottleneck suggests that Whooping Cranes have maintained a capacity to adjust strategies when confronted with future changes in land use and climate.

Asian and European wild boars were independently domesticated ca. 10,000 yr ago. Since the 17th century, Chinese breeds have been imported to Europe to improve the genetics of European animals by introgression of favorable alleles, resulting in a complex mosaic of haplotypes. To interrogate the structure of these haplotypes further, we have run a new haplotype segregation analysis based on information theory, namely compression efficiency (CE). We applied the approach to sequence data from individuals from each phylogeographic region (n = 23 from Asia and Europe) including a number of major pig breeds. Our genome-wide CE is able to discriminate the breeds in a manner reflecting phylogeography. Furthermore, 24,956 nonoverlapping sliding windows (each comprising 1,000 consecutive SNP) were quantified for extent of haplotype sharing within and between Asia and Europe. The genome-wide distribution of extent of haplotype sharing was quite different between groups. Unlike European pigs, Asian pigs haplotype sharing approximates a normal distribution. In line with this, we found the European breeds possessed a number of genomic windows of dramatically higher haplotype sharing than the Asian breeds. Our CE analysis of sliding windows captures some of the genomic regions reported to contain signatures of selection in domestic pigs. Prominent among these regions, we highlight the role of a gene encoding the mitochondrial enzyme LACTB which has been associated with obesity, and the gene encoding MYOG a fundamental transcriptional regulator of myogenesis. The origin of these regions likely reflects either a population bottleneck in European animals, or selective targets on commercial phenotypes reducing allelic diversity in particular genes and/or regulatory regions.

The advent of the genomic era has necessitated the development of methods capable of analyzing large volumes of genomic data efficiently. Being able to reliably identify bottlenecks—extreme population size changes of short duration—not only is interesting in the context of speciation and extinction but also matters (as a null model) when inferring selection. Bottlenecks can be detected in polymorphism data via their distorting effect on the shape of the underlying genealogy. Here, we use the generating function of genealogies to derive the probability of mutational configurations in short sequence blocks under a simple bottleneck model. Given a large number of nonrecombining blocks, we can compute maximum-likelihood estimates of the time and strength of the bottleneck. Our method relies on a simple summary of the joint distribution of polymorphic sites. We extend the site frequency spectrum by counting mutations in frequency classes in short sequence blocks. Using linkage information over short distances in this way gives greater power to detect bottlenecks than the site frequency spectrum and potentially opens up a wide range of demographic histories to blockwise inference. Finally, we apply our method to genomic data from a species of pig (Sus cebifrons) endemic to islands in the center and west of the Philippines to estimate whether a bottleneck occurred upon island colonization and compare our scheme to Li and Durbin’s pairwise sequentially Markovian coalescent (PSMC) both for the pig data and using simulations.

The multiple origins of multicellularity had far-reaching consequences ranging from the appearance of phenotypically complex life-forms to their effects on Earth’s aquatic and terrestrial ecosystems. Yet, many important questions remain. For example, do all lineages and clades share an ancestral developmental predisposition for multicellularity emerging from genomic and biophysical motifs shared from a last common ancestor, or are the multiple origins of multicellularity truly independent evolutionary events? In this review, we highlight recent developments and pitfalls in understanding the evolution of multicellularity with an emphasis on plants (here defined broadly to include the polyphyletic algae), but also draw upon insights from animals and their holozoan relatives, fungi and amoebozoans. Based on our review, we conclude that the evolution of multicellular organisms requires three phases (origination by disparate cell–cell attachment modalities, followed by integration by lineage-specific physiological mechanisms, and autonomization by natural selection) that have been achieved differently in different lineages., The evolution of multicellular organisms, which requires three phases (origination, integration, and autonomization), has been achieved differently in different lineages.

Colonization at expanding range edges often involves few founders, reducing effective population size. This process can promote the evolution of self-fertilization, but implicating historical processes as drivers of trait evolution is often difficult and requires an explicit model of biogeographic history. In plants, contemporary limits to outcrossing are often invoked as evolutionary drivers of self-fertilization, but historical expansions may shape mating system diversity, with leading-edge populations evolving elevated selfing ability. In a widespread plant, Campanula americana, we identified a glacial refugium in the southern Appalachian Mountains from spatial patterns of genetic drift among 24 populations. Populations farther from this refugium have smaller effective sizes and fewer rare alleles. They also displayed elevated heterosis in among-population crosses, reflecting the accumulation of deleterious mutations during range expansion. Although populations with elevated heterosis had reduced segregating mutation load, the magnitude of inbreeding depression lacked geographic pattern. The ability to self-fertilize was strongly positively correlated with the distance from the refugium and mutation accumulation—a pattern that contrasts sharply with contemporary mate and pollinator limitation. In this and other species, diversity in sexual systems may reflect the legacy of evolution in small, colonizing populations, with little or no relation to the ecology of modern populations.

Ailanthus altissima is a common tree species of the European non-native flora. In Eastern Austria, Ailanthus has both a long tradition, dating back to the late 18th century, and a high frequency of occurrence. Here, we apply molecular markers from the nuclear and chloroplast DNA in order to study the origin, as well as the clonal and genetic structure of the species in forest stands of this region. Our results indicate a single area of origin for all our study populations from the north-eastern part of the native range, in agreement with historical reports. Within populations, vegetative reproduction has resulted in extensive clonal structures at some sites. Long presence and repeated vegetative recruitment might have led to expansion of clones in areas of early introduction. In addition, limited mate availability may also have promoted vegetative reproduction. Tests for recent bottlenecks were significant in almost all stands, possibly reflecting founder effects since the introduction of Ailanthus in our study area. Among populations, we found a very pronounced and significant genetic structure, which did not follow a spatial pattern. We argue that founder effects due to population establishment with a low number of propagules – whether naturally or artificially – have caused genetic drift and a structured gene pool. The lack of spatial pattern or isolation-by-distance suggests that seed transfer by humans might have been a major factor shaping the genetic variation of Ailanthus in Eastern Austria.

Alkali bees (Nomia melanderi) are solitary relatives of the halictine bees, which have become an important model for the evolution of social behavior, but for which few solitary comparisons exist. These ground-nesting bees defend their developing offspring against pathogens and predators, and thus exhibit some of the key traits that preceded insect sociality. Alkali bees are also efficient native pollinators of alfalfa seed, which is a crop of major economic value in the United States. We sequenced, assembled, and annotated a high-quality draft genome of 299.6 Mbp for this species. Repetitive content makes up more than one-third of this genome, and previously uncharacterized transposable elements are the most abundant type of repetitive DNA. We predicted 10,847 protein coding genes, and identify 479 of these undergoing positive directional selection with the use of population genetic analysis based on low-coverage whole genome sequencing of 19 individuals. We found evidence of recent population bottlenecks, but no significant evidence of population structure. We also identify 45 genes enriched for protein translation and folding, transcriptional regulation, and triglyceride metabolism evolving slower in alkali bees compared to other halictid bees. These resources will be useful for future studies of bee comparative genomics and pollinator health research.

Direct coupling analysis of nucleotide coevolution provides a novel approach to identify which nucleotides in an RNA molecule are likely in direct contact, and this information obtained from sequence only can be used to predict RNA 3D structures with much improved accuracy. Here we present an efficient method that incorporates this information into current RNA 3D structure prediction methods, specifically 3dRNA. Our method makes much more accurate RNA 3D structure prediction than the original 3dRNA as well as other existing prediction methods that used the direct coupling analysis. In particular our method demonstrates a significant improvement in predicting multi-branch junction conformations, a major bottleneck for RNA 3D structure prediction. We also show that our method can be used to optimize the predictions by other methods. These results indicate that optimization of RNA 3D structure prediction using evolutionary restraints of nucleotide–nucleotide interactions from direct coupling analysis offers an efficient way for accurate RNA tertiary structure predictions.

When a population goes through a small bottleneck, the genetic variability of the population is expected to decline rapidly, but as soon as population size becomes large, it starts to increase owing to new mutations (Wright, 1931; Mayr, 1954). Recently, Nei et al. (1975) studied this problem mathematically and showed that the pattern of change in genetic variability largely depends on the size of bottleneck, rate of population growth, and mutation rate. They provided a general formula for computing the average heterozygosity per locus in a population of changing size. This study is based on the assumption that new mutations occurring in a population are always different from the preexisting ones (Kimura and Crow's (1964) infinite allele model). This assumption seems to be roughly correct if allelic differences are studied at the nucleotide or codon level. In practice, however, the genetic variability of natural populations is usually studied by electrophoretic mobility of proteins. Electrophoretic mobility of a protein is determined mainly by the net charge of the protein, and a positive or negative change in the net charge due to an amino acid substitution may be canceled by the second opposite charge change. Therefore, strictly speaking, the infinite allele model is not appropriate for the study of protein variation detected by electrophoresis. In view of this circumstance, Ohta and Kimura (1973) introduced the so-called stepwise mutation model. In this model each allele is represented as one of the infinite sequence of allelic states and mutation is assumed to produce a one-step change in either the positive or the negative direction. They derived a formula for average heterozygosity in an equilibrium population. Later, Wehrhahn (1975) and Li (1976) extended Ohta and Kimura's work to the case of nonequilibrium populations. On the other hand, Nei and Chakraborty (1973) studied the expected genetic distance between two populations when these are separated for an arbitrary number of generations, using a similar genetic model. The purpose of the present paper is to study the bottleneck effects on average heterozygosity and genetic distance by using the stepwise mutation model. Some studies on the bottleneck effect (the effect of reduction in population size) on genetic distance have been made by Chakraborty and Nei (1974) and Nei (1976), using the infinite allele model. These authors have shown that the reduction in population size results in an accelerated increase in genetic distance in the early generations. In the present paper we shall employ the method of generating function first used by Nei and Chakraborty (1973) in the study of protein variation and extended considerably by Wehrhahn ( 19 7 5).

Trap-based surveillance strategies are widely used for monitoring of invasive insect species, aiming to detect newly arrived exotic taxa as well as track the population levels of established or endemic pests. Where these surveillance traps have low specificity and capture non-target endemic species in excess of the target pests, the need for extensive specimen sorting and identification creates a major diagnostic bottleneck. While the recent development of standardized molecular diagnostics has partly alleviated this requirement, the single specimen per reaction nature of these methods does not readily scale to the sheer number of insects trapped in surveillance programmes. Consequently, target lists are often restricted to a few high-priority pests, allowing unanticipated species to avoid detection and potentially establish populations.DNA metabarcoding has recently emerged as a method for conducting simultaneous, multi-species identification of complex mixed communities and may lend itself ideally to rapid diagnostics of bulk insect trap samples. Moreover, the high-throughput nature of recent sequencing platforms could enable the multiplexing of hundreds of diverse trap samples on a single flow cell, thereby providing the means to dramatically scale up insect surveillance in terms of both the quantity of traps that can be processed concurrently and number of pest species that can be targeted. In this review of the metabarcoding literature, we explore how DNA metabarcoding could be tailored to the detection of invasive insects in a surveillance context and highlight the unique technical and regulatory challenges that must be considered when implementing high-throughput sequencing technologies into sensitive diagnostic applications.

Human immunodeficiency virus type 1 (HIV-1) undergoes a severe population bottleneck during sexual transmission and yet adapts extremely rapidly to the earliest immune responses. The bottleneck has been inferred to typically consist of a single genome, and typically eight amino acid mutations in viral proteins spread to fixation by the end of the early chronic phase of infection in response to selection by CD8+ T cells. Stochastic simulation was used to examine the effects of the transmission bottleneck and of potential interference among spreading immune-escape mutations on the adaptive dynamics of the virus in early infection. If major viral population genetic parameters are assigned realistic values that permit rapid adaptive evolution, then a bottleneck of a single genome is not inconsistent with the observed pattern of adaptive fixations. One requirement is strong selection by CD8+ T cells that decreases over time. Such selection may reduce effective population sizes at linked loci through genetic hitchhiking. However, this effect is predicted to be minor in early infection because the transmission bottleneck reduces the effective population size to such an extent that the resulting strong selection and weak mutation cause beneficial mutations to fix sequentially and thus avoid interference.