Unusual pattern of nucleotide sequence variation at the OS-E and OS-F genomic regions of Drosophila simulans

Nucleotide variation at the genomic region encompassing the odorant-binding protein genes OS-E and OS-F (OS region) was surveyed in two populations of Drosophila simulans, one from Europe and the other from Africa. We found that the European population shows an atypical and large haplotype structure, which extends throughout the approximately 5-kb surveyed genomic region. This structure is depicted by two major haplotype groups segregating at intermediate frequency in the sample, one haplogroup with nearly no variation, and the other at levels more typical for this species. This pattern of variation was incompatible with neutral predictions for a population at a stationary equilibrium. Nevertheless, neutrality tests contrasting polymorphism and divergence data fail to detect any departure from the standard neutral model in this species, whereas they confirm the non-neutral behavior previously observed at the OS-E gene in D. melanogaster. Although positive Darwinian selection may have been responsible for the observed unusual nucleotide variation structure, coalescent simulation results do not allow rejecting the hypothesis that the pattern was generated by a recent bottleneck in the history of European populations of D. simulans.     

Campora: a young genetic isolate in South Italy

Genetic isolates have been successfully used in the study of complex traits, mainly because due to their features, they allow a reduction in the complexity of the genetic models underlying the trait. The aim of the present study is to describe the population of Campora, a village in the South of Italy, highlighting its properties of a genetic isolate. Both historical evidence and multi-locus genetic data (genomic and mitochondrial DNA polymorphisms) have been taken into account in the analyses. The extension of linkage disequilibrium (LD) regions has been evaluated on autosomes and on a region of the X chromosome. We defined a study sample population on the basis of the genealogy and exogamy data. We found in this population a few different mitochondrial and Y chromosome haplotypes and we ascertained that, similarly to other isolated populations, in Campora LD extends over wider region compared to large and genetically heterogeneous populations. These findings indicate a conspicuous genetic homogeneity in the genome. Finally, we found evidence for a recent population bottleneck that we propose to interpret as a demographic crisis determined by the plague of the 17th century. Overall our findings demonstrate that Campora displays the genetic characteristics of a young isolate.     

Sequence Variation within the KIV-2 Copy Number Polymorphism of the Human LPA Gene in African,Asian, and European Populations

Amazingly little sequence variation is reported for the kringle IV 2 copy number variation (KIV 2 CNV) in the human LPA gene. Apart from whole genome sequencing projects, this region has only been analyzed in some detail in samples of European populations. We have performed a systematic resequencing study of the exonic and flanking intron regions within the KIV 2 CNV in 90 alleles from Asian, European, and four different African populations. Alleles have been separated according to their CNV length by pulsed field gel electrophoresis prior to unbiased specific PCR amplification of the target regions. These amplicons covered all KIV 2 copies of an individual allele simultaneously. In addition, cloned amplicons from genomic DNA of an African individual were sequenced. Our data suggest that sequence variation in this genomic region may be higher than previously appreciated. Detection probability of variants appeared to depend on the KIV 2 copy number of the analyzed DNA and on the proportion of copies carrying the variant. Asians had a high frequency of so-called KIV 2 type B and type C (together 70% of alleles), which differ by three or two synonymous substitutions respectively from the reference type A. This is most likely explained by the strong bottleneck suggested to have occurred when modern humans migrated to East Asia. A higher frequency of variable sites was detected in the Africans. In particular, two previously unreported splice site variants were found. One was associated with non-detectable Lp(a). The other was observed at high population frequencies (10% to 40%). Like the KIV 2 type B and C variants, this latter variant was also found in a high proportion of KIV 2 repeats in the affected alleles and in alleles differing in copy numbers. Our findings may have implications for the interpretation of SNP analyses in other repetitive loci of the human genome.     

Inferring the demographic history and rate of adaptive substitution in Drosophila

An important goal of population genetics is to determine the forces that have shaped the pattern of genetic variation in natural populations. We developed a maximum likelihood method that allows us to infer demographic changes and detect recent positive selection (selective sweeps) in populations of varying size from DNA polymorphism data. Applying this approach to single nucleotide polymorphism data at more than 250 noncoding loci on the X chromosome of Drosophila melanogaster from an (ancestral) African population and a (derived) European, we found that the African population expanded about 60,000 y ago and that the European population split off from the African lineage about 15,800 y ago, thereby suffering a severe population size bottleneck. We estimated that about 160 beneficial mutations (with selection coefficients s between 0.05% and 0.5%) were fixed in the euchromatic portion of the X in the African population since population size expansion, and about 60 mutations (with s around 0.5%) in the diverging European lineage.     

Historical and Contemporary DNA Indicate Fisher Decline and Isolation Occurred Prior to the European Settlement of California

Establishing if species contractions were the result of natural phenomena or human induced landscape changes is essential for managing natural populations. Fishers (Martes pennanti) in California occur in two geographically and genetically isolated populations in the northwestern mountains and southern Sierra Nevada. Their isolation is hypothesized to have resulted from a decline in abundance and distribution associated with European settlement in the 1800s. However, there is little evidence to establish that fisher occupied the area between the two extant populations at that time. We analyzed 10 microsatellite loci from 275 contemporary and 21 historical fisher samples (1880–1920) to evaluate the demographic history of fisher in California. We did not find any evidence of a recent (post-European) bottleneck in the northwestern population. In the southern Sierra Nevada, genetic subdivision within the population strongly influenced bottleneck tests. After accounting for genetic subdivision, we found a bottleneck signal only in the northern and central portions of the southern Sierra Nevada, indicating that the southernmost tip of these mountains may have acted as a refugium for fisher during the anthropogenic changes of the late 19^th and early 20^th centuries. Using a coalescent-based Bayesian analysis, we detected a 90% decline in effective population size and dated the time of decline to over a thousand years ago. We hypothesize that fisher distribution in California contracted to the two current population areas pre-European settlement, and that portions of the southern Sierra Nevada subsequently experienced another more recent bottleneck post-European settlement.     

Demographic reductions and genetic bottlenecks in humans: minisatellite allele distributions in oceania

Polynesians have lower heterozygosities at minisatellite VNTR (Variable Number of Tandem Repeat) loci than have Melanesians; this has been taken as evidence of population-size bottlenecks during the colonisation of Polynesia. We have analysed the allelic distribution of several minisatellite loci in the population of Rapa, a Polynesian island that is known to have undergone a demographic reduction of approximately 95% since first contact with European explorers 200 years ago, leaving a surviving population of 120. We found that the minisatellite diversity of this population does not differ significantly from that of other Polynesian populations, and appears consistent with the neutral expectation of diversity assuming the infinite alleles model. This suggests that the demographic crisis that Rapa underwent did not perturb the allele distribution to the extent that the tests used here could detect. Thus we cannot say that a demographic change of this magnitude constitutes a genetic bottleneck detectable at these loci. The reduced diversity seen in Polynesia must therefore be explained either by more severe bottlenecks as might be expected during colonisation, or else by other causes.     

Migratory Flyways May Affect Population Structure in Double-Crested Cormorants

Double-crested cormorants (Phalacrocorax auritus) recovered from a demographic bottleneck so well that they are now considered a nuisance species at breeding and wintering grounds across the United States and Canada. Management of this species could be improved by refining genetic population boundaries and assigning individuals to their natal population. Further, recent radio-telemetry data suggest the existence of Interior and Atlantic migratory flyways, which could reduce gene flow and result in substantial genetic isolation. In this study, we used 1,784 individuals collected across the eastern United States, a large panel of microsatellite markers developed for this species, and individuals banded as chicks and recaptured as adults to explore the effects of migratory flyways on population structure, quantify the genetic effects of demographic bottlenecks, and determine whether individuals could be assigned to their natal population based on genotype. We found evidence for genetic population division only along migratory flyways, no evidence of genetic bottlenecks, and mixed effectiveness of assignment tests. Our population structure findings suggest that gene flow is high across large scales; for example, individuals from New York, Minnesota, and Alabama are all in panmixia. We also found that traditional subspecies ranges may not be valid because >1 subspecies was present in single genetic populations. The lack of evidence for genetic bottlenecks also likely underscores the vagility of this species, suggesting that even during demographic bottlenecks, populations were not isolated from allelic exchange. Finally, the failure of assignment tests to consistently perform is likely due in part to imperfect a priori sampling of Atlantic and Interior chicks and the high vagility of adults. We conclude that the demographic bottleneck is not likely to have reduced genetic diversity, and that assignment tests remain unreliable for this species. We recommend double-crested cormorants be managed by flyway. Further development of genomic resources in this species could improve population subdivision resolution, improve assignment tests, and reveal further information on demographic histories. © 2020 The Wildlife Society.     

No apparent genetic bottleneck in the demographically declining European eel using molecular genetics and forward-time simulations

The stock of the European eel is considered to be outside safe biological limits, following a dramatic demographic decline in recent decades (90–99% drop) that involves a large number of factors including overfishing, contaminants and environmental fluctuations. The aim of the present study is to estimate the effective population size of the European eel and the possible existence of a genetic bottleneck, which is expected during or after a severe demographic crash. Using a panel of 22 EST-derived microsatellite loci, we found no evidence for a genetic bottleneck in the European eel as our data showed moderate to high levels of genetic diversity, no loss of allele size range or rare alleles, and a stationary population with growth values not statistically different from zero, which is confirmed by finding comparable value of short-term and long-term effective population size. Our results suggest that the observed demographic decline in the European eel did not entail a genetic decline of the same magnitude. Forward-time simulations confirmed that large exploited marine fish populations can undergo genetic bottleneck episodes and experience a loss of genetic variability. Simulations indicated that the failure to pick up the signal of a genetic bottleneck in the European eel is not due to lack of power. Although anthropogenic factors lowered the continental stock biomass, the observation of a stable genetic effective population size suggests that the eel crash was not due to a reduction in spawning stock abundance. Alternatively, we propose that overfishing, pollution and/or parasites might have affected individual fitness and fecundity, leading to an impoverished spawning stock that may fail to produce enough good quality eggs. A reduced reproduction success due to poor quality of the spawners may be exacerbated by oceanic processes inducing changes in primary production in the Sargasso Sea and/or pathway of transport across the Atlantic Ocean leading to a higher larval mortality.     

Beans in Europe: origin and structure of the European landraces of Phaseolus vulgaris L.

This study focuses on the expansion of Phaseolus vulgaris in Europe. The pathways of distribution of beans into and across Europe were very complex, with several introductions from the New World that were combined with direct exchanges between European and other Mediterranean countries. We have analyzed here six chloroplast microsatellite (cpSSR) loci and two unlinked nuclear loci (for phaseolin types and Pv-shatterproof1). We have assessed the genetic structure and level of diversity of a large collection of European landraces of P. vulgaris (307) in comparison to 94 genotypes from the Americas that are representative of the Andean and Mesoamerican gene pools. First, we show that most of the European common bean landraces (67%) are of Andean origin, and that there are no strong differences across European regions for the proportions of the Andean and Mesoamerican gene pools. Moreover, cytoplasmic diversity is evenly distributed across European regions. Secondly, the cytoplasmic bottleneck that was due to the introduction of P. vulgaris into the Old World was very weak or nearly absent. This is in contrast to evidence from nuclear analyses that have suggested a bottleneck of greater intensity. Finally, we estimate that a relatively high proportion of the European bean germplasm (about 44%) was derived from hybridization between the Andean and Mesoamerican gene pools. Moreover, although hybrids are present everywhere in Europe, they show an uneven distribution, with high frequencies in central Europe, and low frequencies in Spain and Italy. On the basis of these data, we suggest that the entire European continent and not only some of the countries therein can be regarded as a secondary diversification center for P. vulgaris. Finally, we outline the relevance of these inter-gene pool hybrids for plant breeding.     

Genome-wide association studies provide new insights into type 2 diabetes aetiology

Human geneticists are currently in the middle of a race. Thanks to a new technology in the form of 'genome-wide chips', investigators can potentially find many novel disease genes in one large experiment. Type 2 diabetes has been hot out of the blocks with six recent publications that together provide convincing evidence for six new gene regions involved in the condition. Together with candidate approaches, these studies have identified 11 confirmed genomic regions that alter the risk of type 2 diabetes in the European population. One of these regions, the fat mass and obesity associated gene (FTO), represents by far the best example of an association between common variation and fat mass in the general population.     

Distinctly different sex ratios in African and European populations of Drosophila melanogaster inferred from chromosomewide single nucleotide polymorphism data

It has been hypothesized that the ratio of X-linked to autosomal sequence diversity is influenced by unequal sex ratios in Drosophila melanogaster populations. We conducted a genome scan of single nucleotide polymorphism (SNP) of 378 autosomal loci in a derived European population and of a subset of 53 loci in an ancestral African population. On the basis of these data and our already available X-linked data, we used a coalescent-based maximum-likelihood method to estimate sex ratios and demographic histories simultaneously for both populations. We confirm our previous findings that the African population experienced a population size expansion while the European population suffered a population size bottleneck. Our analysis also indicates that the female population size in Africa is larger than or equal to the male population size. In contrast, the European population shows a huge excess of males. This unequal sex ratio and the bottleneck alone, however, cannot account for the overly strong decrease of X-linked diversity in the European population (compared to the reduction on the autosome). The patterns of the frequency spectrum and the levels of linkage disequilibrium observed in Europe suggest that, in addition, positive selection must have acted in the derived population.     

Linkage disequilibria and the site frequency spectra in the su(s) and su(w(a)) regions of the Drosophila melanogaster X chromosome

Over the last decade, surveys of DNA sequence variation in natural populations of several Drosophila species and other taxa have established that polymorphism is reduced in genomic regions characterized by low rates of crossing over per physical length. Parallel studies have also established that divergence between species is not reduced in these same genomic regions, thus eliminating explanations that rely on a correlation between the rates of mutation and crossing over. Several theoretical models (directional hitchhiking, background selection, and random environment) have been proposed as population genetic explanations. In this study samples from an African population (n = 50) and a European population (n = 51) were surveyed at the su(s) (1955 bp) and su(w(a)) (3213 bp) loci for DNA sequence polymorphism, utilizing a stratified SSCP/DNA sequencing protocol. These loci are located near the telomere of the X chromosome, in a region of reduced crossing over per physical length, and exhibit a significant reduction in DNA sequence polymorphism. Unlike most previously surveyed, these loci reveal substantial skews toward rare site frequencies, consistent with the predictions of directional hitchhiking and random environment models and inconsistent with the general predictions of the background selection model (or neutral theory). No evidence for excess geographic differentiation at these loci is observed. Although linkage disequilibrium is observed between closely linked sites within these loci, many recombination events in the genealogy of the sampled alleles can be inferred and the genomic scale of linkage disequilibrium, measured in base pairs between sites, is the same as that observed for loci in regions of normal crossing over. We conclude that gene conversion must be high in these regions of low crossing over.     

Coding sequence polymorphism in avian mitochondrial genomes reflects population histories

Nucleotide sequence diversity at mitochondrial protein-coding loci from 72 species of birds from different geographical regions was analysed in order to test the hypothesis that temperate zone species show population genetic effects of past glaciation. Temperate zone species showed reduced nucleotide diversity in comparison to tropical mainland species, suggesting that the latter have long-term effective population sizes due to population bottleneck effects during the most recent glaciation. This hypothesis was further supported by evidence of an unusually high estimated rate of population growth in species breeding in North America and wintering in the New World tropics (Nearctic migrants), consistent with population expansion after a bottleneck. Nearctic migrants also showed evidence of an abundance of rare nonsynonymous (amino acid-altering) polymorphisms, a pattern suggesting that slightly deleterious polymorphisms drifted to high frequencies during a bottleneck and are now being eliminated by selection. Because the shape of the North American land mass limited the area available for refugia during glaciation, the bottleneck effects are predicted to have been particularly strong in Nearctic migrants, and this prediction was supported. The reduced genetic diversity of Nearctic migrants provides an additional basis for concern for the survival of these species, which are threatened by loss of habitat in the winter range and by introduced disease.     

Copy number variation across European populations

Genome analysis provides a powerful approach to test for evidence of genetic variation within and between geographical regions and local populations. Copy number variants which comprise insertions, deletions and duplications of genomic sequence provide one such convenient and informative source. Here, we investigate copy number variants from genome wide scans of single nucleotide polymorphisms in three European population isolates, the island of Vis in Croatia, the islands of Orkney in Scotland and the South Tyrol in Italy. We show that whereas the overall copy number variant frequencies are similar between populations, their distribution is highly specific to the population of origin, a finding which is supported by evidence for increased kinship correlation for specific copy number variants within populations.     

Partitioning of genetic variation across the genome using multimarker methods in a wild bird population

The underlying basis of genetic variation in quantitative traits, in terms of the number of causal variants and the size of their effects, is largely unknown in natural populations. The expectation is that complex quantitative trait variation is attributable to many, possibly interacting, causal variants, whose effects may depend upon the sex, age and the environment in which they are expressed. A recently developed methodology in animal breeding derives a value of relatedness among individuals from high‐density genomic marker data, to estimate additive genetic variance within livestock populations. Here, we adapt and test the effectiveness of these methods to partition genetic variation for complex traits across genomic regions within ecological study populations where individuals have varying degrees of relatedness. We then apply this approach for the first time to a natural population and demonstrate that genetic variation in wing length in the great tit (Parus major) reflects contributions from multiple genomic regions. We show that a polygenic additive mode of gene action best describes the patterns observed, and we find no evidence of dosage compensation for the sex chromosome. Our results suggest that most of the genomic regions that influence wing length have the same effects in both sexes. We found a limited amount of genetic variance in males that is attributed to regions that have no effects in females, which could facilitate the sexual dimorphism observed for this trait. Although this exploratory work focuses on one complex trait, the methodology is generally applicable to any trait for any laboratory or wild population, paving the way for investigating sex‐, age‐ and environment‐specific genetic effects and thus the underlying genetic architecture of phenotype in biological study systems.     

Haplotype structure in Ashkenazi Jewish BRCA1 and BRCA2 mutation carriers

Three founder mutations in BRCA1 and BRCA2 contribute to the risk of hereditary breast and ovarian cancer in Ashkenazi Jews (AJ). They are observed at increased frequency in the AJ compared to other BRCA mutations in Caucasian non-Jews (CNJ). Several authors have proposed that elevated allele frequencies in the surrounding genomic regions reflect adaptive or balancing selection. Such proposals predict long-range linkage disequilibrium (LD) resulting from a selective sweep, although genetic drift in a founder population may also act to create long-distance LD. To date, few studies have used the tools of statistical genomics to examine the likelihood of long-range LD at a deleterious locus in a population that faced a genetic bottleneck. We studied the genotypes of hundreds of women from a large international consortium of BRCA1 and BRCA2 mutation carriers and found that AJ women exhibited long-range haplotypes compared to CNJ women. More than 50% of the AJ chromosomes with the BRCA1 185delAG mutation share an identical 2.1?Mb haplotype and nearly 16% of AJ chromosomes carrying the BRCA2 6174delT mutation share a 1.4?Mb haplotype. Simulations based on the best inference of Ashkenazi population demography indicate that long-range haplotypes are expected in the context of a genome-wide survey. Our results are consistent with the hypothesis that a local bottleneck effect from population size constriction events could by chance have resulted in the large haplotype blocks observed at high frequency in the BRCA1 and BRCA2 regions of Ashkenazi Jews.     

Low worldwide genetic diversity in the basking shark (Cetorhinus maximus)

The basking shark (Cetorhinus maximus) is found in temperate waters throughout the world's oceans, and has been subjected to extensive exploitation in some regions. However, little is known about its current abundance and genetic status. Here, we investigate the diversity of the mitochondrial DNA control region among samples from the western North Atlantic, eastern North Atlantic, Mediterranean Sea, Indian Ocean and western Pacific. We find just six haplotypes defined by five variable sites, a comparatively low genetic diversity of pi=0.0013 and no significant differentiation between ocean basins. We provide evidence for a bottleneck event within the Holocene, estimate an effective population size (Ne) that is low for a globally distributed species, and discuss the implications.     

Demography and natural selection have shaped genetic variation in Drosophila melanogaster: a multi-locus approach

Demography and selection have been recognized for their important roles in shaping patterns of nucleotide variability. To investigate the relative effects of these forces in the genome of Drosophila melanogaster, we used a multi-locus scan (105 fragments) of X-linked DNA sequence variation in a putatively ancestral African and a derived European population. Surprisingly, we found evidence for a recent size expansion in the African population, i.e., a significant excess of singletons at a chromosome-wide level. In the European population, such an excess was not detected. In contrast to the African population, we found evidence for positive natural selection in the European sample: (i) a large number of loci with low levels of variation and (ii) a significant excess of derived variants at the low-variation loci that are fixed in the European sample but rare in the African population. These results are consistent with the hypothesis that the European population has experienced frequent selective sweeps in the recent past during its adaptation to new habitats. Our study shows the advantages of a genomic approach (over a locus-specific analysis) in disentangling demographic and selective forces.     

Evidence for a selective sweep in the wapl region of Drosophila melanogaster

A scan of the X chromosome of a European Drosophila melanogaster population revealed evidence for the recent action of positive directional selection at individual loci. In this study we analyze one such region that showed no polymorphism in the genome scan (located in cytological division 2C10-2E1). We detect a 60.5-kb stretch of DNA encompassing the genes ph-d, ph-p, CG3835, bcn92, Pgd, wapl, and Cyp4d1, which almost completely lacks variation in the European sample. Loci flanking this region show a skewed frequency spectrum at segregating sites, strong haplotype structure, and high levels of linkage disequilibrium. Neutrality tests reveal that these data are unlikely under both the neutral equilibrium model and the simple bottleneck scenarios. In contrast, newly developed maximum-likelihood ratio tests suggest that strong selection has acted recently on the region under investigation, causing a selective sweep. Evidence that this sweep may have originated in an ancestral population in Africa is presented.