Publications by authors named "Andrea Benazzo"

27 Publications

  • Page 1 of 1

Population structure, genomic diversity and demographic history of Komodo dragons inferred from whole-genome sequencing.

Mol Ecol 2021 Aug 14. Epub 2021 Aug 14.

Department of Biology, University of Florence, Firenze, Italy.

Population and conservation genetics studies have greatly benefited from the development of new techniques and bioinformatic tools associated with next-generation sequencing. Analysis of extensive data sets from whole-genome sequencing of even a few individuals allows the detection of patterns of fine-scale population structure and detailed reconstruction of demographic dynamics through time. In this study, we investigated the population structure, genomic diversity and demographic history of the Komodo dragon (Varanus komodoensis), the world's largest lizard, by sequencing the whole genomes of 24 individuals from the five main Indonesian islands comprising the entire range of the species. Three main genomic groups were observed. The populations of the Island of Komodo and the northern coast of Flores, in particular, were identified as two distinct conservation units. Degrees of genomic divergence among island populations were interpreted as a result of changes in sea level affecting connectivity across islands. Demographic inference suggested that Komodo dragons probably experienced a relatively steep population decline over the last million years, reaching a relatively stable N during the Saalian glacial cycle (400-150 thousand years ago) followed by a rapid N decrease. Genomic diversity of Komodo dragons was similar to that found in endangered or already extinct reptile species. Overall, this study provides an example of how whole-genome analysis of a few individuals per population can help define population structure and intraspecific demographic dynamics. This is particularly important when applying population genomics data to conservation of rare or elusive endangered species.
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http://dx.doi.org/10.1111/mec.16121DOI Listing
August 2021

Divergence and hybridization in sea turtles: Inferences from genome data show evidence of ancient gene flow between species.

Mol Ecol 2021 Aug 13. Epub 2021 Aug 13.

Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.

Reconstructing past events of hybridization and population size changes are required to understand speciation mechanisms and current patterns of genetic diversity, and ultimately contribute to species' conservation. Sea turtles are ancient species currently facing anthropogenic threats including climate change, fisheries, and illegal hunting. Five of the seven extant sea turtle species are known to currently hybridize, especially along the Brazilian coast where some populations can have ~32%-42% of hybrids. Although frequently observed today, it is not clear what role hybridization plays in the evolutionary diversification of this group of reptiles. In this study, we generated whole genome resequencing data of the five globally distributed sea turtle species to estimate a calibrated phylogeny and the population size dynamics, and to understand the role of hybridization in shaping the genomes of these ancient species. Our results reveal discordant species divergence dates between mitochondrial and nuclear genomes, with a high frequency of conflicting trees throughout the nuclear genome suggesting that some sea turtle species frequently hybridized in the past. The reconstruction of the species' demography showed a general decline in effective population sizes with no signs of recovery, except for the leatherback sea turtle. Furthermore, we discuss the influence of reference bias in our estimates. We show long-lasting ancestral gene flow events within Chelonioidea that continued for millions of years after initial divergence. Speciation with gene flow is a common pattern in marine species, and it raises questions whether current hybridization events should be considered as a part of these species' evolutionary history or a conservation issue.
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http://dx.doi.org/10.1111/mec.16113DOI Listing
August 2021

Ancient genomes reveal early Andean farmers selected common beans while preserving diversity.

Nat Plants 2021 02 8;7(2):123-128. Epub 2021 Feb 8.

Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.

All crops are the product of a domestication process that started less than 12,000 years ago from one or more wild populations. Farmers selected desirable phenotypic traits (such as improved energy accumulation, palatability of seeds and reduced natural shattering) while leading domesticated populations through several more or less gradual demographic contractions. As a consequence, the erosion of wild genetic variation is typical of modern cultivars, making them highly susceptible to pathogens, pests and environmental change. The loss of genetic diversity hampers further crop improvement programmes to increase food production in a changing world, posing serious threats to food security. Using both ancient and modern seeds, we analysed the temporal dynamics of genetic variation and selection during the domestication process of the common bean (Phaseolus vulgaris) in the southern Andes. Here, we show that most domestic traits were selected for before 2,500 years ago, with no or only minor loss of whole-genome heterozygosity. In fact, most of the changes at coding genes and linked regions that differentiate wild and domestic genomes are already present in the ancient genomes analysed here, and all ancient domestic genomes dated between 600 and 2,500 years ago are highly variable (at least as variable as modern genomes from the wild). Single seeds from modern cultivars show reduced variation when compared with ancient seeds, indicating that intensive selection within cultivars in the past few centuries probably partitioned ancestral variation within different genetically homogenous cultivars. When cultivars from different Andean regions are pooled, the genomic variation of the pool is higher than that observed in the pool of ancient seeds from north and central western Argentina. Considering that most desirable phenotypic traits are probably controlled by multiple polymorphic genes, a plausible explanation of this decoupling of selection and genetic erosion is that early farmers applied a relatively weak selection pressure by using many phenotypically similar but genetically diverse individuals as parents. Our results imply that selection strategies during the past few centuries, as compared with earlier times, more intensively reduced genetic variation within cultivars and produced further improvements by focusing on a few plants carrying the traits of interest, at the cost of marked genetic erosion within Andean landraces.
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http://dx.doi.org/10.1038/s41477-021-00848-7DOI Listing
February 2021

A Revised Model of Anatomically Modern Human Expansions Out of Africa through a Machine Learning Approximate Bayesian Computation Approach.

Genes (Basel) 2020 12 16;11(12). Epub 2020 Dec 16.

Department of Life Sciences and Biotechnology, University of Ferrara, 44121 Ferrara, Italy.

There is a wide consensus in considering Africa as the birthplace of anatomically modern humans (AMH), but the dispersal pattern and the main routes followed by our ancestors to colonize the world are still matters of debate. It is still an open question whether AMH left Africa through a single process, dispersing almost simultaneously over Asia and Europe, or in two main waves, first through the Arab Peninsula into southern Asia and Australo-Melanesia, and later through a northern route crossing the Levant. The development of new methodologies for inferring population history and the availability of worldwide high-coverage whole-genome sequences did not resolve this debate. In this work, we test the two main out-of-Africa hypotheses through an Approximate Bayesian Computation approach, based on the Random-Forest algorithm. We evaluated the ability of the method to discriminate between the alternative models of AMH out-of-Africa, using simulated data. Once assessed that the models are distinguishable, we compared simulated data with real genomic variation, from modern and archaic populations. This analysis showed that a model of multiple dispersals is four-fold as likely as the alternative single-dispersal model. According to our estimates, the two dispersal processes may be placed, respectively, around 74,000 and around 46,000 years ago.
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http://dx.doi.org/10.3390/genes11121510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766041PMC
December 2020

Distinguishing among complex evolutionary models using unphased whole-genome data through random forest approximate Bayesian computation.

Mol Ecol Resour 2020 Sep 30. Epub 2020 Sep 30.

Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.

Inferring past demographic histories is crucial in population genetics, and the amount of complete genomes now available should in principle facilitate this inference. In practice, however, the available inferential methods suffer from severe limitations. Although hundreds complete genomes can be simultaneously analysed, complex demographic processes can easily exceed computational constraints, and the procedures to evaluate the reliability of the estimates contribute to increase the computational effort. Here we present an approximate Bayesian computation framework based on the random forest algorithm (ABC-RF), to infer complex past population processes using complete genomes. To this aim, we propose to summarize the data by the full genomic distribution of the four mutually exclusive categories of segregating sites (FDSS), a statistic fast to compute from unphased genome data and that does not require the ancestral state of alleles to be known. We constructed an efficient ABC pipeline and tested how accurately it allows one to recognize the true model among models of increasing complexity, using simulated data and taking into account different sampling strategies in terms of number of individuals analysed, number and size of the genetic loci considered. We also compared the FDSS with the unfolded and folded site frequency spectrum (SFS), and for these statistics we highlighted the experimental conditions maximizing the inferential power of the ABC-RF procedure. We finally analysed real data sets, testing models on the dispersal of anatomically modern humans out of Africa and exploring the evolutionary relationships of the three species of Orangutan inhabiting Borneo and Sumatra.
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http://dx.doi.org/10.1111/1755-0998.13263DOI Listing
September 2020

A randomized comparison between Accuro and palpation-guided spinal anesthesia for obese patients undergoing orthopedic surgery.

Reg Anesth Pain Med 2019 Oct 25. Epub 2019 Oct 25.

Anesthesia, Intensive Care and Pain Therapy, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.

Background: Although obese patients benefit from neuraxial anesthesia, technical difficulties often discourage its use. The current randomized trial compared Accuro, a hand-held, battery-operated ultrasound (US) device, and conventional palpation for spinal anesthesia in obese patients undergoing orthopedic surgery. We hypothesized that Accuro would decrease the number of needle redirections.

Methods: We enrolled 130 men and women with a body mass index ≥30 kg/m, scheduled for lower limb surgery under spinal block. Patients were randomized either to the Control group (group C: spinal block after palpation of cutaneous landmarks) or to the Accuro group (group A: preprocedural US scan with Accuro to identify the needle insertion point). The procedural time, the number of skin passes and of needle redirections, the occurrence of failure and adverse events were recorded.

Results: Ninety-nine patients completed the study. Patients in group Accuro showed a median (IQR) number of redirections of 3 (0-9) and a median (IQR) number of needle passes through the skin of 1 (1-2) versus 6 (1-16) and 1 (1-3), respectively, in group Control (p=0.008, p=0.019). The performance time was 558±232 s in group Accuro versus 348±255 s in group Control (p<0.001). There were no intergroup differences in terms of failed blocks and adverse events.

Conclusions: The use of Accuro reduced the number of needle redirections and passes through the skin when performing spinal anesthesia, but required a longer procedural time.

Trial Registration Number: ClinicalTrials.gov registry (NCT03075488).
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http://dx.doi.org/10.1136/rapm-2019-100538DOI Listing
October 2019

Low-Frequency and Rare Variants in Italian Multiple Sclerosis Patients.

Front Genet 2019 26;10:573. Epub 2019 Jun 26.

Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.

In light of the complex nature of multiple sclerosis (MS) and the recently estimated contribution of low-frequency variants into disease, decoding its genetic risk components requires novel variant prioritization strategies. We selected, by reviewing MS Genome Wide Association Studies (GWAS), 107 candidate loci marked by intragenic single nucleotide polymorphisms (SNPs) with a remarkable association (-value ≤ 5 × 10). A whole exome sequencing (WES)-based pilot study of SNPs with minor allele frequency (MAF) ≤ 0.04, conducted in three Italian families, revealed 15 exonic low-frequency SNPs with affected parent-child transmission. These variants were detected in 65/120 Italian unrelated MS patients, also in combination (22 patients). Compared with databases (controls gnomAD, dbSNP150, ExAC, Tuscany-1000 Genome), the allelic frequencies of rs16870005 and rs12722600 were significantly higher (i.e., controls gnomAD, = 9.89 × 10 and < 1 × 10). rs61744960 and rs138943371 frequencies were also significantly higher, except in Tuscany-1000 Genome. Interestingly, the association of rs16870005 (Ala431Thr) with MS did not depend on its linkage disequilibrium with the locus. Sequencing in the MS cohort of the 3' region revealed 14 rare mutations (10 not previously reported). Four variants were null, and significantly more frequent than in the databases. Further, the rare variants were observed in combinations, both intra-locus and with other low-frequency SNPs. The Ser389Xfr was found homozygous in a patient with early onset of the MS. Taking into account the potentially functional impact of the identified exonic variants, their expression in combination at the protein level could provide functional insights in the heterogeneous pathogenetic mechanisms contributing to MS.
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http://dx.doi.org/10.3389/fgene.2019.00573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6607989PMC
June 2019

Genetic diversity of CHC22 clathrin impacts its function in glucose metabolism.

Elife 2019 06 4;8. Epub 2019 Jun 4.

Research Department of Structural and Molecular Biology, Division of Biosciences, University College London, London, United Kingdom.

CHC22 clathrin plays a key role in intracellular membrane traffic of the insulin-responsive glucose transporter GLUT4 in humans. We performed population genetic and phylogenetic analyses of the CHC22-encoding gene, revealing independent gene loss in at least two vertebrate lineages, after arising from gene duplication. All vertebrates retained the paralogous gene encoding CHC17 clathrin, which mediates endocytosis. For vertebrates retaining , strong evidence for purifying selection supports CHC22 functionality. All human populations maintained two high frequency allelic variants, encoding either methionine or valine at position 1316. Functional studies indicated that CHC22-V1316, which is more frequent in farming populations than in hunter-gatherers, has different cellular dynamics than M1316-CHC22 and is less effective at controlling GLUT4 membrane traffic, altering its insulin-regulated response. These analyses suggest that ancestral human dietary change influenced selection of allotypes that affect CHC22's role in metabolism and have potential to differentially influence the human insulin response.
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http://dx.doi.org/10.7554/eLife.41517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6548504PMC
June 2019

Survival and divergence in a small group: The extraordinary genomic history of the endangered Apennine brown bear stragglers.

Proc Natl Acad Sci U S A 2017 11 24;114(45):E9589-E9597. Epub 2017 Oct 24.

Department of Life Sciences and Biotechnology, University of Ferrara, 44121 Ferrara, Italy;

About 100 km east of Rome, in the central Apennine Mountains, a critically endangered population of ∼50 brown bears live in complete isolation. Mating outside this population is prevented by several 100 km of bear-free territories. We exploited this natural experiment to better understand the gene and genomic consequences of surviving at extremely small population size. We found that brown bear populations in Europe lost connectivity since Neolithic times, when farming communities expanded and forest burning was used for land clearance. In central Italy, this resulted in a 40-fold population decline. The overall genomic impact of this decline included the complete loss of variation in the mitochondrial genome and along long stretches of the nuclear genome. Several private and deleterious amino acid changes were fixed by random drift; predicted effects include energy deficit, muscle weakness, anomalies in cranial and skeletal development, and reduced aggressiveness. Despite this extreme loss of diversity, Apennine bear genomes show nonrandom peaks of high variation, possibly maintained by balancing selection, at genomic regions significantly enriched for genes associated with immune and olfactory systems. Challenging the paradigm of increased extinction risk in small populations, we suggest that random fixation of deleterious alleles () can be an important driver of divergence in isolation, () can be tolerated when balancing selection prevents random loss of variation at important genes, and () is followed by or results directly in favorable behavioral changes.
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http://dx.doi.org/10.1073/pnas.1707279114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5692547PMC
November 2017

Leukocyte Esterase Strip Test Can Predict Subsequent Failure Following Reimplantation in Patients With Periprosthetic Joint Infection.

J Arthroplasty 2017 06 26;32(6):1976-1979. Epub 2017 Jan 26.

The Rothman Institute at Thomas Jefferson University, Philadelphia, Pennsylvania.

Background: Leukocyte esterase (LE) strip test is an accurate marker for diagnosing periprosthetic joint infection (PJI). This study aims to determine if LE is a good predictor of persistent infection and/or subsequent failure in patients undergoing reimplantation.

Methods: This single-institution study prospectively recruited and retrospectively analyzed 109 patients who underwent two-stage exchange treatment of PJI, from 2009-2016, and had an LE test performed at time of reimplantation. LE results of "2+" were considered positive. Ninety-five patients had 90-day minimum follow-up to assess treatment failure, defined by Delphi criteria. Eighteen patients were excluded due to blood contamination of LE test, resulting in a final cohort of 77 patients (mean follow-up 1.76 years).

Results: Of the final cohort, 19 patients (24.7%) experienced subsequent failure. At reimplantation, LE test was positive in 22.2% of culture-positive and 4.4% of culture-negative cases. The LE test was negative in all patients who had not failed at latest follow-up, yielding sensitivity, specificity, positive predictive value, negative predictive value, and AUC of 26.3%, 100%, 100%, 87.5%, and 0.632, respectively; in comparison, MSIS criteria respectively yielded 25.0%, 87.3%, 27.6%, 85.8%, and 0.562 (P = .01 for specificity). Kaplan-Meier curves revealed higher failure rate in patients who had a positive LE test at time of reimplantation (P < .001).

Conclusion: There is a dire need for an accurate diagnostic test to determine optimal timing of reimplantation in patients undergoing surgical treatment for PJI. The current study suggests that a positive LE test may be indicative of persistence of infection and results in a higher rate of subsequent failure.
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http://dx.doi.org/10.1016/j.arth.2017.01.031DOI Listing
June 2017

High Level of Nonsynonymous Changes in Common Bean Suggests That Selection under Domestication Increased Functional Diversity at Target Traits.

Front Plant Sci 2016 6;7:2005. Epub 2017 Jan 6.

Department of Agricultural, Food and Environmental Sciences, Università Politecnica delle Marche Ancona, Italy.

Crop species have been deeply affected by the domestication process, and there have been many efforts to identify selection signatures at the genome level. This knowledge will help geneticists to better understand the evolution of organisms, and at the same time, help breeders to implement successful breeding strategies. Here, we focused on domestication in the Mesoamerican gene pool of by sequencing 49 gene fragments from a sample of 45 wild and domesticated accessions, and as controls, two accessions each of the closely related species and . An excess of nonsynonymous mutations within the domesticated germplasm was found. Our data suggest that the cost of domestication alone cannot explain fully this finding. Indeed, the significantly higher frequency of polymorphisms in the coding regions observed only in the domesticated plants (compared to noncoding regions), the fact that these mutations were mostly nonsynonymous and appear to be recently derived mutations, and the investigations into the functions of their relative genes (responses to biotic and abiotic stresses), support a scenario that involves new functional mutations selected for adaptation during domestication. Moreover, consistent with this hypothesis, selection analysis and the possibility to compare data obtained for the same genes in different studies of varying sizes, data types, and methodologies allowed us to identify four genes that were strongly selected during domestication. Each selection candidate is involved in plant resistance/tolerance to abiotic stresses, such as heat, drought, and salinity. Overall, our study suggests that domestication acted to increase functional diversity at target loci, which probably controlled traits related to expansion and adaptation to new agro-ecological growing conditions.
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http://dx.doi.org/10.3389/fpls.2016.02005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5216878PMC
January 2017

Chimpanzee genomic diversity reveals ancient admixture with bonobos.

Science 2016 10 27;354(6311):477-481. Epub 2016 Oct 27.

Section for Computational and RNA Biology, Department of Biology, University of Copenhagen, 2200 Copenhagen, Denmark.

Our closest living relatives, chimpanzees and bonobos, have a complex demographic history. We analyzed the high-coverage whole genomes of 75 wild-born chimpanzees and bonobos from 10 countries in Africa. We found that chimpanzee population substructure makes genetic information a good predictor of geographic origin at country and regional scales. Multiple lines of evidence suggest that gene flow occurred from bonobos into the ancestors of central and eastern chimpanzees between 200,000 and 550,000 years ago, probably with subsequent spread into Nigeria-Cameroon chimpanzees. Together with another, possibly more recent contact (after 200,000 years ago), bonobos contributed less than 1% to the central chimpanzee genomes. Admixture thus appears to have been widespread during hominid evolution.
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http://dx.doi.org/10.1126/science.aag2602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5546212PMC
October 2016

Demographic History of the Genus Pan Inferred from Whole Mitochondrial Genome Reconstructions.

Genome Biol Evol 2016 07 3;8(6):2020-30. Epub 2016 Jul 3.

Departament de Ciències Experimentals i de la Salut, Institut de Biologia Evolutiva (CSIC-UPF), Barcelona, Spain Catalan Institution of Research and Advanced Studies (ICREA), Passeig de Lluís Companys, Barcelona, Spain CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain

The genus Pan is the closest genus to our own and it includes two species, Pan paniscus (bonobos) and Pan troglodytes (chimpanzees). The later is constituted by four subspecies, all highly endangered. The study of the Pan genera has been incessantly complicated by the intricate relationship among subspecies and the statistical limitations imposed by the reduced number of samples or genomic markers analyzed. Here, we present a new method to reconstruct complete mitochondrial genomes (mitogenomes) from whole genome shotgun (WGS) datasets, mtArchitect, showing that its reconstructions are highly accurate and consistent with long-range PCR mitogenomes. We used this approach to build the mitochondrial genomes of 20 newly sequenced samples which, together with available genomes, allowed us to analyze the hitherto most complete Pan mitochondrial genome dataset including 156 chimpanzee and 44 bonobo individuals, with a proportional contribution from all chimpanzee subspecies. We estimated the separation time between chimpanzees and bonobos around 1.15 million years ago (Mya) [0.81-1.49]. Further, we found that under the most probable genealogical model the two clades of chimpanzees, Western + Nigeria-Cameroon and Central + Eastern, separated at 0.59 Mya [0.41-0.78] with further internal separations at 0.32 Mya [0.22-0.43] and 0.16 Mya [0.17-0.34], respectively. Finally, for a subset of our samples, we compared nuclear versus mitochondrial genomes and we found that chimpanzee subspecies have different patterns of nuclear and mitochondrial diversity, which could be a result of either processes affecting the mitochondrial genome, such as hitchhiking or background selection, or a result of population dynamics.
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http://dx.doi.org/10.1093/gbe/evw124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4943195PMC
July 2016

Full circumpolar migration ensures evolutionary unity in the Emperor penguin.

Nat Commun 2016 06 14;7:11842. Epub 2016 Jun 14.

Centre for Ecological and Evolutionary Synthesis (CEES), Department of Biosciences, University of Oslo, Postboks, Blindern, Oslo 1066, Norway.

Defining reliable demographic models is essential to understand the threats of ongoing environmental change. Yet, in the most remote and threatened areas, models are often based on the survey of a single population, assuming stationarity and independence in population responses. This is the case for the Emperor penguin Aptenodytes forsteri, a flagship Antarctic species that may be at high risk continent-wide before 2100. Here, using genome-wide data from the whole Antarctic continent, we reveal that this top-predator is organized as one single global population with a shared demography since the late Quaternary. We refute the view of the local population as a relevant demographic unit, and highlight that (i) robust extinction risk estimations are only possible by including dispersal rates and (ii) colony-scaled population size is rather indicative of local stochastic events, whereas the species' response to global environmental change is likely to follow a shared evolutionary trajectory.
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http://dx.doi.org/10.1038/ncomms11842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4911614PMC
June 2016

Recent Selection Changes in Human Genes under Long-Term Balancing Selection.

Mol Biol Evol 2016 06 1;33(6):1435-47. Epub 2016 Feb 1.

Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany

Balancing selection is an important evolutionary force that maintains genetic and phenotypic diversity in populations. Most studies in humans have focused on long-standing balancing selection, which persists over long periods of time and is generally shared across populations. But balanced polymorphisms can also promote fast adaptation, especially when the environment changes. To better understand the role of previously balanced alleles in novel adaptations, we analyzed in detail four loci as case examples of this mechanism. These loci show hallmark signatures of long-term balancing selection in African populations, but not in Eurasian populations. The disparity between populations is due to changes in allele frequencies, with intermediate frequency alleles in Africans (likely due to balancing selection) segregating instead at low- or high-derived allele frequency in Eurasia. We explicitly tested the support for different evolutionary models with an approximate Bayesian computation approach and show that the patterns in PKDREJ, SDR39U1, and ZNF473 are best explained by recent changes in selective pressure in certain populations. Specifically, we infer that alleles previously under long-term balancing selection, or alleles linked to them, were recently targeted by positive selection in Eurasian populations. Balancing selection thus likely served as a source of functional alleles that mediated subsequent adaptations to novel environments.
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http://dx.doi.org/10.1093/molbev/msw023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4909129PMC
June 2016

The Biarzo case in northern Italy: is the temporal dynamic of swine mitochondrial DNA lineages in Europe related to domestication?

Sci Rep 2015 Nov 9;5:16514. Epub 2015 Nov 9.

Dipartimento di Scienze della Vita e Biotecnologie, Università di Ferrara, Ferrara, Italy.

Genetically-based reconstructions of the history of pig domestication in Europe are based on two major pillars: 1) the temporal changes of mitochondrial DNA lineages are related to domestication; 2) Near Eastern haplotypes which appeared and then disappeared in some sites across Europe are genetic markers of the first Near Eastern domestic pigs. We typed a small but informative fragment of the mitochondrial DNA in 23 Sus scrofa samples from a site in north eastern Italy (Biarzo shelter) which provides a continuous record across a ≈6,000 year time frame from the Upper Palaeolithic to the Neolithic. We additionally carried out several radiocarbon dating. We found that a rapid mitochondrial DNA turnover occurred during the Mesolithic, suggesting that substantial changes in the composition of pig mitochondrial lineages can occur naturally across few millennia independently of domestication processes. Moreover, so-called Near Eastern haplotypes were present here at least two millennia before the arrival of Neolithic package in the same area. Consequently, we recommend a re-evaluation of the previous idea that Neolithic farmers introduced pigs domesticated in the Near East, and that Mesolithic communities acquired domestic pigs via cultural exchanges, to include the possibility of a more parsimonious hypothesis of local domestication in Europe.
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http://dx.doi.org/10.1038/srep16514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4637886PMC
November 2015

Across language families: Genome diversity mirrors linguistic variation within Europe.

Am J Phys Anthropol 2015 Aug 8;157(4):630-40. Epub 2015 Jun 8.

Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.

Objectives: The notion that patterns of linguistic and biological variation may cast light on each other and on population histories dates back to Darwin's times; yet, turning this intuition into a proper research program has met with serious methodological difficulties, especially affecting language comparisons. This article takes advantage of two new tools of comparative linguistics: a refined list of Indo-European cognate words, and a novel method of language comparison estimating linguistic diversity from a universal inventory of grammatical polymorphisms, and hence enabling comparison even across different families. We corroborated the method and used it to compare patterns of linguistic and genomic variation in Europe.

Materials And Methods: Two sets of linguistic distances, lexical and syntactic, were inferred from these data and compared with measures of geographic and genomic distance through a series of matrix correlation tests. Linguistic and genomic trees were also estimated and compared. A method (Treemix) was used to infer migration episodes after the main population splits.

Results: We observed significant correlations between genomic and linguistic diversity, the latter inferred from data on both Indo-European and non-Indo-European languages. Contrary to previous observations, on the European scale, language proved a better predictor of genomic differences than geography. Inferred episodes of genetic admixture following the main population splits found convincing correlates also in the linguistic realm.

Discussion: These results pave the ground for previously unfeasible cross-disciplinary analyses at the worldwide scale, encompassing populations of distant language families.
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http://dx.doi.org/10.1002/ajpa.22758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095809PMC
August 2015

Large-scale recent expansion of European patrilineages shown by population resequencing.

Nat Commun 2015 May 19;6:7152. Epub 2015 May 19.

Department of Genetics, University of Leicester, University Road, Leicester LE1 7RH, UK.

The proportion of Europeans descending from Neolithic farmers ∼ 10 thousand years ago (KYA) or Palaeolithic hunter-gatherers has been much debated. The male-specific region of the Y chromosome (MSY) has been widely applied to this question, but unbiased estimates of diversity and time depth have been lacking. Here we show that European patrilineages underwent a recent continent-wide expansion. Resequencing of 3.7 Mb of MSY DNA in 334 males, comprising 17 European and Middle Eastern populations, defines a phylogeny containing 5,996 single-nucleotide polymorphisms. Dating indicates that three major lineages (I1, R1a and R1b), accounting for 64% of our sample, have very recent coalescent times, ranging between 3.5 and 7.3 KYA. A continuous swathe of 13/17 populations share similar histories featuring a demographic expansion starting ∼ 2.1-4.2 KYA. Our results are compatible with ancient MSY DNA data, and contrast with data on mitochondrial DNA, indicating a widespread male-specific phenomenon that focuses interest on the social structure of Bronze Age Europe.
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http://dx.doi.org/10.1038/ncomms8152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4441248PMC
May 2015

4P: fast computing of population genetics statistics from large DNA polymorphism panels.

Ecol Evol 2015 Jan 11;5(1):172-5. Epub 2014 Dec 11.

Department of Life Sciences and Biotechnology, University of Ferrara via L. Borsari, 46, 44100, Ferrara, Italy.

Massive DNA sequencing has significantly increased the amount of data available for population genetics and molecular ecology studies. However, the parallel computation of simple statistics within and between populations from large panels of polymorphic sites is not yet available, making the exploratory analyses of a set or subset of data a very laborious task. Here, we present 4P (parallel processing of polymorphism panels), a stand-alone software program for the rapid computation of genetic variation statistics (including the joint frequency spectrum) from millions of DNA variants in multiple individuals and multiple populations. It handles a standard input file format commonly used to store DNA variation from empirical or simulation experiments. The computational performance of 4P was evaluated using large SNP (single nucleotide polymorphism) datasets from human genomes or obtained by simulations. 4P was faster or much faster than other comparable programs, and the impact of parallel computing using multicore computers or servers was evident. 4P is a useful tool for biologists who need a simple and rapid computer program to run exploratory population genetics analyses in large panels of genomic data. It is also particularly suitable to analyze multiple data sets produced in simulation studies. Unix, Windows, and MacOs versions are provided, as well as the source code for easier pipeline implementations.
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http://dx.doi.org/10.1002/ece3.1261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4298444PMC
January 2015

Bayesian inferences suggest that Amazon Yunga Natives diverged from Andeans less than 5000 ybp: implications for South American prehistory.

BMC Evol Biol 2014 Sep 30;14:174. Epub 2014 Sep 30.

Background: Archaeology reports millenary cultural contacts between Peruvian Coast-Andes and the Amazon Yunga, a rainforest transitional region between Andes and Lower Amazonia. To clarify the relationships between cultural and biological evolution of these populations, in particular between Amazon Yungas and Andeans, we used DNA-sequence data, a model-based Bayesian approach and several statistical validations to infer a set of demographic parameters.

Results: We found that the genetic diversity of the Shimaa (an Amazon Yunga population) is a subset of that of Quechuas from Central-Andes. Using the Isolation-with-Migration population genetics model, we inferred that the Shimaa ancestors were a small subgroup that split less than 5300 years ago (after the development of complex societies) from an ancestral Andean population. After the split, the most plausible scenario compatible with our results is that the ancestors of Shimaas moved toward the Peruvian Amazon Yunga and incorporated the culture and language of some of their neighbors, but not a substantial amount of their genes. We validated our results using Approximate Bayesian Computations, posterior predictive tests and the analysis of pseudo-observed datasets.

Conclusions: We presented a case study in which model-based Bayesian approaches, combined with necessary statistical validations, shed light into the prehistoric demographic relationship between Andeans and a population from the Amazon Yunga. Our results offer a testable model for the peopling of this large transitional environmental region between the Andes and the Lower Amazonia. However, studies on larger samples and involving more populations of these regions are necessary to confirm if the predominant Andean biological origin of the Shimaas is the rule, and not the exception.
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http://dx.doi.org/10.1186/s12862-014-0174-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189748PMC
September 2014

Decreased Nucleotide and Expression Diversity and Modified Coexpression Patterns Characterize Domestication in the Common Bean.

Plant Cell 2014 May 21;26(5):1901-1912. Epub 2014 May 21.

Department of Agricultural, Food, and Environmental Sciences, Università Politecnica delle Marche, 60131 Ancona, Italy Consiglio per la Ricerca e Sperimentazione in Agricoltura, Cereal Research Centre (CRA-CER), 71122 Foggia, Italy

Using RNA sequencing technology and de novo transcriptome assembly, we compared representative sets of wild and domesticated accessions of common bean (Phaseolus vulgaris) from Mesoamerica. RNA was extracted at the first true-leaf stage, and de novo assembly was used to develop a reference transcriptome; the final data set consists of ∼190,000 single nucleotide polymorphisms from 27,243 contigs in expressed genomic regions. A drastic reduction in nucleotide diversity (∼60%) is evident for the domesticated form, compared with the wild form, and almost 50% of the contigs that are polymorphic were brought to fixation by domestication. In parallel, the effects of domestication decreased the diversity of gene expression (18%). While the coexpression networks for the wild and domesticated accessions demonstrate similar seminal network properties, they show distinct community structures that are enriched for different molecular functions. After simulating the demographic dynamics during domestication, we found that 9% of the genes were actively selected during domestication. We also show that selection induced a further reduction in the diversity of gene expression (26%) and was associated with 5-fold enrichment of differentially expressed genes. While there is substantial evidence of positive selection associated with domestication, in a few cases, this selection has increased the nucleotide diversity in the domesticated pool at target loci associated with abiotic stress responses, flowering time, and morphology.
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http://dx.doi.org/10.1105/tpc.114.124040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4079357PMC
May 2014

Impact of type 2 diabetes susceptibility variants on quantitative glycemic traits reveals mechanistic heterogeneity.

Diabetes 2014 Jun 2;63(6):2158-71. Epub 2013 Dec 2.

Wellcome Trust Sanger Institute, Hinxton, U.K.

Patients with established type 2 diabetes display both β-cell dysfunction and insulin resistance. To define fundamental processes leading to the diabetic state, we examined the relationship between type 2 diabetes risk variants at 37 established susceptibility loci, and indices of proinsulin processing, insulin secretion, and insulin sensitivity. We included data from up to 58,614 nondiabetic subjects with basal measures and 17,327 with dynamic measures. We used additive genetic models with adjustment for sex, age, and BMI, followed by fixed-effects, inverse-variance meta-analyses. Cluster analyses grouped risk loci into five major categories based on their relationship to these continuous glycemic phenotypes. The first cluster (PPARG, KLF14, IRS1, GCKR) was characterized by primary effects on insulin sensitivity. The second cluster (MTNR1B, GCK) featured risk alleles associated with reduced insulin secretion and fasting hyperglycemia. ARAP1 constituted a third cluster characterized by defects in insulin processing. A fourth cluster (TCF7L2, SLC30A8, HHEX/IDE, CDKAL1, CDKN2A/2B) was defined by loci influencing insulin processing and secretion without a detectable change in fasting glucose levels. The final group contained 20 risk loci with no clear-cut associations to continuous glycemic traits. By assembling extensive data on continuous glycemic traits, we have exposed the diverse mechanisms whereby type 2 diabetes risk variants impact disease predisposition.
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http://dx.doi.org/10.2337/db13-0949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4030103PMC
June 2014

High variance in reproductive success generates a false signature of a genetic bottleneck in populations of constant size: a simulation study.

BMC Bioinformatics 2013 Oct 16;14:309. Epub 2013 Oct 16.

Department of Life Sciences and Biotechnology, University of Ferrara, via Borsari 46, Ferrara I-44121, Italy.

Background: Demographic bottlenecks can severely reduce the genetic variation of a population or a species. Establishing whether low genetic variation is caused by a bottleneck or a constantly low effective number of individuals is important to understand a species' ecology and evolution, and it has implications for conservation management. Recent studies have evaluated the power of several statistical methods developed to identify bottlenecks. However, the false positive rate, i.e. the rate with which a bottleneck signal is misidentified in demographically stable populations, has received little attention. We analyse this type of error (type I) in forward computer simulations of stable populations having greater than Poisson variance in reproductive success (i.e., variance in family sizes). The assumption of Poisson variance underlies bottleneck tests, yet it is commonly violated in species with high fecundity.

Results: With large variance in reproductive success (Vk ≥ 40, corresponding to a ratio between effective and census size smaller than 0.1), tests based on allele frequencies, allelic sizes, and DNA sequence polymorphisms (heterozygosity excess, M-ratio, and Tajima's D test) tend to show erroneous signals of a bottleneck. Similarly, strong evidence of population decline is erroneously detected when ancestral and current population sizes are estimated with the model based method MSVAR.

Conclusions: Our results suggest caution when interpreting the results of bottleneck tests in species showing high variance in reproductive success. Particularly in species with high fecundity, computer simulations are recommended to confirm the occurrence of a population bottleneck.
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http://dx.doi.org/10.1186/1471-2105-14-309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3852946PMC
October 2013

No evidence of Neandertal admixture in the mitochondrial genomes of early European modern humans and contemporary Europeans.

Am J Phys Anthropol 2011 Oct 24;146(2):242-52. Epub 2011 Aug 24.

Department of Biology and Evolution, University of Ferrara, Italy.

Neandertals, the archaic human form documented in Eurasia until 29,000 years ago, share no mitochondrial haplotype with modern Europeans. Whether this means that the two groups were reproductively isolated is controversial, and indeed nuclear data have been interpreted as suggesting that they admixed. We explored the range of demographic parameters that may have generated the observed mitochondrial diversity, simulating 3.0 million genealogies under six models differing as for the relationships among contemporary Europeans, Neandertals, and Upper Palaeolithic European early modern humans (EEMH), who coexisted with Neandertals for millennia. We compared by Approximate Bayesian Computations the simulation results with mitochondrial diversity in 7 Neandertals, 3 EEMH, and 150 opportunely chosen modern Europeans. A model of genealogical continuity between EEMH and contemporary Europeans, with no Neandertal contribution, received overwhelming support from the analyses. The maximum degree of Neandertal admixture, under the model of gene flow supported by nuclear data, was estimated at 1.5%, but this model proved 20-32 times less likely than a model without any gene flow. Nuclear and mitochondrial evidence might be reconciled if smaller population sizes led to faster lineage sorting for mitochondrial DNA, and Neandertals shared a longer period of common ancestry with the non-African's than with the African's ancestors.
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http://dx.doi.org/10.1002/ajpa.21569DOI Listing
October 2011

Inferring genealogical processes from patterns of Bronze-Age and modern DNA variation in Sardinia.

Mol Biol Evol 2010 Apr 2;27(4):875-86. Epub 2009 Dec 2.

Dipartimento di Biologia ed Evoluzione, Università di Ferrara, Ferrara, Italy.

The ancient inhabitants of a region are often regarded as ancestral, and hence genetically related, to the modern dwellers (for instance, in studies of admixture), but so far, this assumption has not been tested empirically using ancient DNA data. We studied mitochondrial DNA (mtDNA) variation in Sardinia, across a time span of 2,500 years, comparing 23 Bronze-Age (nuragic) mtDNA sequences with those of 254 modern individuals from two regions, Ogliastra (a likely genetic isolate) and Gallura, and considering the possible impact of gene flow from mainland Italy. To understand the genealogical relationships between past and present populations, we developed seven explicit demographic models; we tested whether these models can account for the levels and patterns of genetic diversity in the data and which one does it best. Extensive simulation based on a serial coalescent algorithm allowed us to compare the posterior probability of each model and estimate the relevant evolutionary (mutation and migration rates) and demographic (effective population sizes, times since population splits) parameters, by approximate Bayesian computations. We then validated the analyses by investigating how well parameters estimated from the simulated data can reproduce the observed data set. We show that a direct genealogical continuity between Bronze-Age Sardinians and the current people of Ogliastra, but not Gallura, has a much higher probability than any alternative scenarios and that genetic diversity in Gallura evolved largely independently, owing in part to gene flow from the mainland.
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http://dx.doi.org/10.1093/molbev/msp292DOI Listing
April 2010

Genealogical discontinuities among Etruscan, Medieval, and contemporary Tuscans.

Mol Biol Evol 2009 Sep 1;26(9):2157-66. Epub 2009 Jul 1.

Dipartimento di Biologia Evoluzionistica, Laboratorio di Antropologia, Università di Firenze, Firenze, Italy.

The available mitochondrial DNA (mtDNA) data do not point to clear genetic relationships between current Tuscans and the Bronze-Age inhabitants of Tuscany, the Etruscans. To understand how and when such a genetic discontinuity may have arisen, we extracted and typed the mtDNAs of 27 medieval Tuscans from an initial sample of 61, spanning a period between the 10th and 15th century AD. We then tested by serial coalescent simulation various models describing the genealogical relationships among past and current inhabitants of Tuscany, the latter including three samples (from Murlo, Volterra, and Casentino) that were recently claimed to be of Etruscan descent. Etruscans and medieval Tuscans share three mitochondrial haplotypes but fall in distinct branches of the mitochondrial genealogy in the only model that proved compatible with the data. Under that model, contemporary people of Tuscany show clear genetic relationships with Medieval people, but not with the Etruscans, along the female lines. No evidence of excess mutation was found in the Etruscan DNAs by a Bayesian test, and so there is no reason to suspect that these results are biased by systematic contamination of the ancient sequences or laboratory artefacts. Extensive demographic changes before AD 1000 are thus the simplest explanation for the differences between the contemporary and the Bronze-Age mtDNAs of Tuscany. Accordingly, genealogical continuity between ancient and modern populations of the same area does not seem a safe general assumption, but rather a hypothesis that, when possible, should be tested using ancient DNA analysis.
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http://dx.doi.org/10.1093/molbev/msp126DOI Listing
September 2009
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