Tools in molecular population genetics

The ex situ population of Amur tigers represents one of the best conservation breeding programs of endangered wildlife, as exemplified by 2 well-managed captive populations in North America Species Survival Plan and Europe European Breeding Program , respectively. Established in the early s, these 2 captive breeding programs are now home to over Amur tiger descended from 57 founders Traylor-Holzer The Amur tiger displays the lowest mtDNA diversity among all tiger subspecies.

Extensive sampling of the wild Amur tigers and additional sequencing of the highly variable control region revealed 2 more mtDNA haplotypes, which are different from the widespread haplotype Nevertheless, population structural analysis based on microsatellite allele frequency and heterozygosity clearly identified 2 populations isolated by a development and construction barrier in the Russian Far East and estimated the effective population size at 27—35 Henry et al.

The reduced genetic variability in the Amur tiger is consistent with its peripheral distribution of the entire tiger range and might have resulted from a postglacial colonization of the region in the Lower Pleistocene. By contrast, there is no evidence for a recent population bottleneck associated with the well-documented demographic decline in the 20 th century Henry et al.

The captive breeding programs of Amur tigers have maintained comparable population size and genetic diversity relative to the wild populations in the Russian Far East, yet genetic variants have persisted ex situ that were lost in situ Luo et al. In addition, there are fewer pairs of closely related individuals in the ex situ population than in situ , likely a consequence of the large population size, century-long introduction of new founders, and successful breeding strategies to retain genetic variability in captivity.

Overall, the coordinated captive Amur tigers adequately represent the gene pool of the wild populations and might serve as a healthy supplement to in situ conservation, if population reinforcements become necessary in the future.

Tigers became extinct in Central Asia and the islands of Bali and Java in the mid to late 20 th century and the South China tiger has not been seen in the wild for more than 25 years. Elucidation of the phylogeography and evolutionary history of the living tiger subspecies paved the path for exploring the genetic ancestry of the extinct tigers.

The Caspian tiger P. Using ancient DNA methodology, genetic analysis of over 20 museum specimens indicate a close relationship with the Amur tiger P. Due to their evolutionary proximity, living Amur tigers are likely the closest living genetic stock should reintroductions to the former range of the Caspian tiger be initiated. Indian tigers P. The most recent nationwide tiger census estimated the number of tigers in India at , with the lower and higher bounds at and , respectively Jhala et al.

Despite the significant decline from its census number of , India is home to the largest number of tigers in a single country and plays a critical role in global tiger conservation Jhala et al. In captivity, Indian zoos have been breeding tigers since and currently manage approximately registered individuals.

Based on 5 highly variable microsatellite loci after extensive validation from 30 candidate loci, individual identification was conducted on 58 non-invasively collected tiger scat samples. The study demonstrated the feasibility of generating reliable abundance estimation through genetic surveys of scats in an elusive and rare species such as the tiger.

It also highlighted the importance of rigorous field survey and laboratory protocols for reliable population size estimation with non-invasive sampling. The examples cited in this review represent the major advances of conservation genetics in tigers over the past decade. As genomics technologies evolve, numerous tools for elucidating the origin, variability, divergence, adaptation and survival in free-ranging species are also becoming available. Because all cat species diverged from a common ancestor less than 10 Ma, and because genomic composition is highly conserved in Felidae, the domestic cat genomic resources can be readily applied to nondomestic cat species, including the tiger.

For all these reasons, molecular genetics tools are beginning to resolve many conservation questions in tigers that were previously unachievable: for example, genetic characterization of distinct tiger subspecies, genetic ancestry of the extinct tigers, heritage background of generic captive tigers with unknown origin, population size estimation based on non-invasive sampling and capture—recapture analysis, and demographic history under the influence of geological and human-induced events.

There remain important unanswered questions for tiger systematics, evolution and conservation. What is the extent of population genetic variation, demographic history and population structure among tiger populations across different landscapes? Can forensic applications help trace the geographic origin of illegally traded tiger parts? Are the other recently extinct tiger subspecies as distinctive as the living subspecies?

National Center for Biotechnology Information , U. Integr Zool. Author manuscript; available in PMC Jan Warren E. Stephen J. Author information Copyright and License information Disclaimer. Copyright notice.

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Abstract The utility of molecular genetic approaches in conservation of endangered taxa is now commonly recognized. Keywords: conservation genetics, mitochondrial DNA, microsatellite, subspecies, tiger. Open in a separate window.

Figure 1. Subspecies diagnostic molecular genetic system In , the conclusions of a year study to characterize differences among the extant tiger populations and subspecies were published based on biological samples from voucher tiger specimens Luo et al. Table 1 Polymerase chain reaction primers specific for tiger cytoplasmic mitochondrial DNA amplification.

Primers to amplify a total of 4kb tiger mtDNA fragments Luo et al. Primers to amplify short fragments from historical specimens Driscoll et al.

The obtained sequences are subset of those from Luo et al. Primers to amplify short fragments from scat specimens Mondol et al. Table 2 Nuclear microsatellite markers used in tigers. Reference No. Modified mtDNA marker system for historical tiger specimens Three subspecies, Bali, Caspian and Javan tigers became extinct from their range in the 20 th century, and the South China tiger has not been seen in the wild for over 2 decades.

Modified genetic system for non-invasively collected tiger specimens Non-invasively collected samples, such as hair and scat from wildlife, represent an important source of genetic samples that can be relatively easy to collect from the field. Table 3 Applications of molecular genetics to conservation of the tiger. Malayan tiger: a novel subspecies Panthera tigris jacksoni As with many endangered species, tigers have been classified into subspecies for purposes of recognition and conservation.

Captive tigers: Genetic reservoir of wild tigers Well-managed captive populations of wild animals provide conservation support for their wild relatives in many ways.

Amur tiger: A successful story both in the wild and captivity Understanding of the Amur tiger P. Caspian tiger: Potential for reintroduction of the extinct tigers Tigers became extinct in Central Asia and the islands of Bali and Java in the mid to late 20 th century and the South China tiger has not been seen in the wild for more than 25 years. Indian tiger: Populations genetics based on non-invasive sampling Indian tigers P.

Phylogeography: The History and Formation of Species. Harvard University Press, Cambridge. Genotyping faecal samples of Bengal tiger Panthera tigris tigris for population estimation: A pilot study. BMC Genetics 7 , Why keep tigers in zoos? In: Tilson R, Nyhus P, eds. Sorting out tigers Panthera tigris : Mitochondrial sequences, nuclear inserts, systematics, and conservation genetics. Animal Conservation 1 , — Supermatrix and species tree methods resolve phylogenetic relationships within the big cats, Panthera Carnivora: Felidae.

Molecular Phylogenetics and Evolution 56 , 64— The fate of wild tiger. Bioscience 57 , — Mitochondrial phylogeography illuminates the origin of the extinct Caspian tiger and its relationship to the Amur Tiger.

PLoS One 4 , e Genetic variability and geographic structure of three subspecies of tigers Panthera tigris based on MHC class I variation. Animal Conservation 3 , — In situ population structure and ex situ representation of the endangered Amur tiger. What is the adaptive significance of this amount of positive selection? Positive selection and adaptive selection are typically considered to be synonymous terms.

In genomic regions under HRi, weak deleterious mutations will be repeatedly fixed in the genome, increasing the opportunity for compensatory mutations that restores the harmful effect of the previously fixed deleterious mutations Kimura It could be the case that many variants fixed by positive selection are such compensatory mutations.

These mutations cannot be considered adaptation in a strong evolutionary sense, because adaptation implies an innovative new feature of an organism, while a compensatory change restores a previous trait to its normal function. It is a beneficial change but not an adaptation.

Deleterious and beneficial mutations occur within the context of static DFE or selective equilibrium. An adaptation, however, is defined as a nonequilibrium response to changes in selection that implies a surplus of beneficial over deleterious changes reflected in a time-dependent fitness landscape. If most of the estimated positive selection is due to compensatory substitution, then this evidence says little about adaptation.

If adaptation is a multilevel process that concerts phenotypic-genotypic changes by adjusting multilevel constraints, population genomics data have to be integrated with other phenotypic multi-omics data to obtain a complete picture of how adaptation occurs see The future: Toward a Population -Omics Synthesis. Theoretical predictions and tests for selection applied to genetic variation data are generally based on the assumption that populations are at a demographic equilibrium.

However, demographic fluctuations must occur in every natural population. Most populations of model species studied have experienced recent changes in population sizes, recombination, and other genome features see section Geographic differentiation and demographic history.

If the equilibrium assumption is violated, estimates of both positive and deleterious selection can be seriously biased Jensen et al. For example, in a population that has suffered a bottleneck followed by an exponential growth, deleterious mutations reach equilibrium frequencies more quickly than neutral mutations, which can be interpreted as an excess of segregating deleterious variants in the population when applying a test for selection Brandvain and Wright N e is a parameter that captures long-term population dynamics.

N e is usually estimated from the levels of standing variation, which is very sensitive to past bottleneck events. Because the number of new beneficial mutations entering a population at a given moment depends on the census population size, focusing on N e to assess the adaptive potential of a species can be seriously misleading. Consider the key insecticide resistance locus Ace in D.

It evolved quickly, repeatedly incorporating resistance alleles within individual populations Karasov et al. This observation has two important consequences: 1 adaptation in Drosophila may not be limited by waiting for beneficial mutations at single sites; and 2 multiple convergent mutations or standing variants can be fixed, leaving a weaker signature on the pattern of variation, the so-called soft sweep Karasov et al.

In contrast, the standard sweeps of positive directional selection, also called hard sweeps, assume a mutation-limited scenario where a single beneficial mutation is selected in each iterative sweep, leaving a stronger footprint on the pattern of variation. The relative incidence of hard vs. Population genomics studies to date have been limited to the genotypic space: the description of genome variation patterns of individuals of different populations and species, while trying to discern the relative importance of the evolutionary forces modeling these patterns.

However, natural selection acts primarily on the phenotype, while leaving its footprint on the genotype. The genomic dimension, albeit necessary, is not sufficient to account for a complete picture, retrospective and prospective He and Liu , of organismal adaptation Lewontin Recent advances in NGS technologies have boosted the breadth of available -omics data, from the genomic level to epigenomic, transcriptomic, proteomic, or metabolomic data.

These different -omics layers, which in contrast to the genomic sequence vary during the lifetime of an individual and in different parts of the body, represent intermediate phenotypes between the genomic space and the final organismal phenotype on which natural selection operates Civelek and Lusis While a single -omics layer can only provide limited insight into how different evolutionary forces have shaped this particular -omics layer through their action on the phenotype; the integration of multiple -omics layers across time and space e.

The description and integrative analysis of intra- and interpopulation genome-wide multi-omics data are now feasible and should soon provide a unified fitness—phenotype—genotype map on which to extend the population genetics theory toward a systemic evolutionary theory.

Population genetics is no longer an empirically insufficient science, but it is more than ever a research field where bioinformatics tools for data mining and management of large-scale data sets, statistical and evolutionary models, and advanced molecular techniques of massive generation of sequences are all integrated in an interdisciplinary endeavor.

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Genetics 49 : 49 — Amount of variation and degree of heterozygosity in natural populations of Drosophila pseudoobscura. Genetics 54 : — Evolution 14 : — Genetics 74 : — Genetics 90 : — Bioinformatics 25 : — BMC Syst. Sinauer Associates, Inc. Genetica : 3 — Henry Holt and Company , New York. Sign In. Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. Drosophila as a Model Organism for Population Genetics.

Patterns of Genome Variation. Determinants of Patterns of Genome Variation. Population Genomics Challenges. Literature Cited. Molecular Population Genetics. Institut de Biotecnologia i de Biomedicina. Oxford Academic. Antonio Barbadilla. E-mail: antonio. Select Format Select format.

Permissions Icon Permissions. Abstract Molecular population genetics aims to explain genetic variation and molecular evolution from population genetics principles. Drosophila , molecular population genetics , population genomics , neutral theory , distribution of fitness effects , genetic draft , linked selection , Hill—Robertson interference , population multi-omics , FlyBook.

Open in new tab Download slide. Box 1. Open in new tab. Last version. Supported alignment formats. Supported SNP data formats. DnaSP 5. Box 2. The rate of molecular evolution K is the speed at which genome changes are incorporated fixed in a given species in each generation.

If genome divergence is the final evolutionary consequence of the molecular population dynamics, then K informs about the rhythm at which species diverge through their evolutionary time Figure 3. K is the fixation rate averaged over all mutations entering the population. Each of these new mutations have a given selection coefficient s that is determined by its fitness effect on the individual DFE, Figure 3A.

All mutations with this s , f s , have a probability of fixation that depends both on the population census and the effective population size, in addition to the selection coefficient, u N , N e , s thus contributing to the divergence between species Kimura ; Figure 3B.

Communicating editor: T. Reduced variation in the yellow - achaete - scute region in natural populations of Drosophila melanogaster.

Restriction-map variation at the zeste - tko region in natural populations of Drosophila melanogaster. Polymorphism and divergence in the Mst26A male accessory gland gene region in Drosophila.

Population history and natural selection shape patterns of genetic variation in genes. Pesticide resistance via transposition-mediated adaptive gene truncation in Drosophila. Chromosome-scale selective sweeps shape Caenorhabditis elegans genomic diversity.

Hitchhiking effects of recurrent beneficial amino acid substitutions in the Drosophila melanogaster genome. Molecular population genetics of the Alcohol dehydrogenase gene region of Drosophila melanogaster. Intraspecific phylogeography: the mitochondrial DNA bridge between population genetics and systematics.

Death of PRDM9 coincides with stabilization of the recombination landscape in the dog genome. Genetic variation in natural populations of five Drosophila species and the hypothesis of the selective neutrality of protein polymorphisms.

Selection, recombination and demographic history in Drosophila miranda. Effects of X-linkage and sex-biased gene expression on the rate of adaptive protein evolution in Drosophila. Nucleotide variation of the Est-6 gene region in natural populations of Drosophila melanogaster.

Molecular population genetics of the beta-esterase gene cluster of Drosophila melanogaster. Nucleotide variation in the tinman and bagpipe homeobox genes of Drosophila melanogaster. On the abundance and distribution of transposable elements in the genome of Drosophila melanogaster.

Population size does not influence mitochondrial genetic diversity in animals. Levels of naturally occurring DNA polymorphism correlate with recombination rates in D.

Population genomics: whole-genome analysis of polymorphism and divergence in Drosophila simulans. Seasonal variation in life history traits in two Drosophila species. Lack of polymorphism on the Drosophila fourth chromosome resulting from selection. Detecting selection in population trees: the Lewontin and Krakauer test extended. The hitchhiking effect on the site frequency spectrum of DNA polymorphisms.

Identification of regions of positive selection using shared genomic segment analysis. The relation between recombination rate and patterns of molecular evolution and variation in Drosophila melanogaster. Whole-genome sequencing of multiple Arabidopsis thaliana populations. PDA v. DPDB: a database for the storage, representation and analysis of polymorphism in the Drosophila genus. Purifying selection maintains highly conserved noncoding sequences in Drosophila.

Adaptive evolution is substantially impeded by Hill-Robertson interference in Drosophila. Genome-wide fine-scale recombination rate variation in Drosophila melanogaster. The effect of background selection against deleterious mutations on weakly selected, linked variants. The distribution of transposable elements within and between chromosomes in a population of Drosophila melanogaster. The pattern of neutral molecular variation under the background selection model.

The effects of local selection, balanced polymorphism and background selection on equilibrium patterns of genetic diversity in subdivided populations. Hubby and Lewontin on protein variation in natural populations: when molecular genetics came to the rescue of population genetics. Cis-regulatory elements in the Accord retrotransposon result in tissue-specific expression of the Drosophila melanogaster insecticide resistance gene Cyp6g1.

Background selection as baseline for nucleotide variation across the Drosophila genome. Intragenic Hill-Robertson interference influences selection intensity on synonymous mutations in Drosophila.

The correlation between intron length and recombination in Drosophila. The Hill-Robertson effect: evolutionary consequences of weak selection and linkage in finite populations. The many landscapes of recombination in Drosophila melanogaster. Adaptive protein evolution of X-linked and autosomal genes in Drosophila : implications for faster-X hypotheses. Natural selection constrains neutral diversity across a wide range of species.

Abundance and distribution of transposable elements in two Drosophila QTL mapping resources. Genomic signatures of selection at linked sites: unifying the disparity among species. A single p allele associated with insecticide resistance in Drosophila. Distribution of hobo transposable elements in the genus Drosophila. Drosophila 12 Genomes Consortium,. Demographic inference reveals African and European admixture in the North American Drosophila melanogaster population.

Standard and generalized McDonald-Kreitman test: a website to detect selection by comparing different classes of DNA sites.

Dosage compensation via transposable element mediated rewiring of a regulatory network. Arlequin suite ver 3. Analysis of molecular variance inferred from metric distances among DNA haplotypes: application to human mitochondrial DNA restriction data.

Arlequin version 3. Estimating the rate of adaptive molecular evolution in the presence of slightly deleterious mutations and population size change. Detecting signatures of selection through haplotype differentiation among hierarchically structured populations.

Population genomics of the fission yeast Schizosaccharomyces pombe. Genomics of clinal variation in Drosophila : disentangling the interactions of selection and demography. A genome-scan method to identify selected loci appropriate for both dominant and codominant markers: a Bayesian perspective.

Patterns of linkage disequilibrium and long range hitchhiking in evolving experimental Drosophila melanogaster populations. Statistical tests of neutrality of mutations against population growth, hitchhiking and background selection. Multiple reference genomes and transcriptomes for Arabidopsis thaliana. Genome diversity and divergence in Drosophila mauritiana : multiple signatures of faster X evolution.

Elevation of linkage disequilibrium above neutral expectations in ancestral and derived populations of Drosophila melanogaster. Recent selective sweeps in North American Drosophila melanogaster show signatures of soft sweeps. High rate of recent transposable element-induced adaptation in Drosophila melanogaster. A recent adaptive transposable element insertion near highly conserved developmental loci in Drosophila melanogaster. Genome wide analyses reveal little evidence for adaptive evolution in many plant species.

Global diversity lines - a five-continent reference panel of sequenced Drosophila melanogaster strains. The transposable element Bari-Jheh mediates oxidative stress response in Drosophila. Fifteen years of genomewide scans for selection: trends, lessons and unaddressed genetic sources of complication.

Reduced efficacy of selection in regions of the Drosophila genome that lack crossing over. Estimating the parameters of selection on nonsynonymous mutations in Drosophila pseudoobscura and D. Using identity by descent estimation with dense genotype data to detect positive selection. Screening for recently selected alleles by analysis of human haplotype similarity. Population genomics of the honey bee reveals strong signatures of positive selection on worker traits.

Nucleotide variation in the triosephosphate isomerase Tpi locus of Drosophila melanogaster and Drosophila simulans. A flexible forward simulator for populations subject to selection and demography. Natural variation in genome architecture among Drosophila melanogaster Genetic Reference Panel lines. Estimating the recombination parameter of a finite population model without selection. Statistical properties of the number of recombination events in the history of a sample of DNA sequences.

Evidence for positive selection in the superoxide dismutase Sod region of Drosophila melanogaster. Distinctly different sex ratios in African and European populations of Drosophila melanogaster inferred from chromosomewide single nucleotide polymorphism data.

Distinguishing between selective sweeps and demography using DNA polymorphism data. Evidence that adaptation in Drosophila is not limited by mutation at single sites. What can we learn about the distribution of fitness effects of new mutations from DNA sequence data? Inferring the frequency spectrum of derived variants to quantify adaptive molecular evolution in protein-coding genes of Drosophila melanogaster.

Hybrid dysgenesis in Drosophila melanogaster : factors affecting chromosomal contamination in the P-M system. Detecting a local signature of genetic hitchhiking along a recombining chromosome. Stochastic processes and distribution of gene frequencies under natural selection. Properties and power of the Drosophila Synthetic Population Resource for the routine dissection of complex traits. Sequencing of pooled DNA samples Pool-Seq uncovers complex dynamics of transposable element insertions in Drosophila melanogaster.

A comparison of models to infer the distribution of fitness effects of new mutations. Recombination Chapter 5. Population Structure Chapter 6. The Coalescent Chapter 7. Direct Selection Chapter 8. Linked Selection Chapter 9. Demographic History Chapter Population Genomics. Related Titles.

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