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The power and promise of population genomics: from genotyping to genome typing

Key Points

  • Genome typing is the simultaneous genotyping of tens to hundreds of marker loci from across the genome in a single or few experiments (for example, by PCR amplification).

  • The population-genomics approach of genome typing followed by testing for outlier loci can identify candidate-selected loci and improve inferences about population demographic and evolutionary history.

  • Outlier loci (for example, loci with excessively high Fst, Fis or homozygosity excess) can severely bias estimates of population parameters (for example, Fst, migration rates (Nm), population size and phylogeny) if they are not identified and removed before parameter estimation.

  • Genome typing is becoming increasingly feasible, even in non-model taxa, thanks to new molecular techniques such as DArT (microarrays), gene-targeted AFLP and expressed sequence tag (EST) databases.

  • Improved statistical methodologies such as 'summary statistics' will facilitate analyses of large population-genomic data sets.

  • Statistical tests and software programs for detecting outlier loci and analysing population-genomic data are becoming increasingly available; nonetheless, the development and validation of tests and software is the greatest impediment to the advancement of population-genomic approaches.

  • The population-genomics paradigm can facilitate biodiversity conservation through rapid biodiversity screening, identifying appropriate populations for translocations (to rescue declining populations) and focusing conservation efforts on preserving processes of evolution (adaptive change).

  • This review focuses largely on non-model organisms, natural populations and biodiversity conservation, and therefore complements recent reviews of population-genomic approaches in medical genomics and pharmacogenomics in humans and model organisms.

Abstract

Population genomics has the potential to improve studies of evolutionary genetics, molecular ecology and conservation biology, by facilitating the identification of adaptive molecular variation and by improving the estimation of important parameters such as population size, migration rates and phylogenetic relationships. There has been much excitement in the recent literature about the identification of adaptive molecular variation using the population-genomic approach. However, the most useful contribution of the genomics model to population genetics will be improving inferences about population demography and evolutionary history.

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Figure 1: Flow chart of the four main steps in the population-genomic approach.
Figure 2: Identifying outlier behaviour.
Figure 3: Examples of outlier behaviour.
Figure 4: The effect of outlier loci on phylogenetic inference.

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Acknowledgements

We thank F. Allendorf, M. Beaumont, T. Mitchell-Olds, K. Schmidt, P. Sunnucks and three anonymous reviewers for providing references, discussions and helpful comments. W. Amos and J. W. Grahame provided unpublished data and correspondence. S.J. and D.T. were funded by the United States National Science Foundation. G.L, P.R.E and P.T. were supported in part by the European Union ('Econogene' project).

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Correspondence to Gordon Luikart.

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The authors declare that they have no competing financial interests.

Related links

Related links

Databases

LocusLink

MC1R

Further information

DetSel software (Renaud Vitalis's web site)

Fdist software (Mark Beaumont's web site)

GeneClass2

Illumina

LECA web site

Neutrallelix

PyPop software

Zhenshan Wang's web site

Glossary

RANDOM GENETIC DRIFT

Random fluctuations in allele frequencies between generations owing to sampling effects. It increases as the effective population size decreases.

GENE FLOW

The movement of genes among populations. Often expressed as the proportion of gene copies (or breeding individuals) that are immigrants from a different population.

BOTTLENECK

A marked reduction in population size that often results in the loss of genetic variation and more frequent matings among closely related individuals.

MICROEVOLUTION

Evolutionary processes or changes over relatively short time periods — such as change in allele frequencies, genotypic composition or gene expression — within or between populations.

F ST

The most widely used index of genetic divergence between populations. A standardized measure of the distribution of genetic variation between populations on a scale between 0 (identical allele frequencies in populations) and 1 (populations fixed for different alleles).

NEUTRAL LOCI

Loci that are not evolving directly in response to selection, the dynamics of which are controlled mainly by genetic drift and migration. These loci can, however, be influenced by selection on nearby (linked) loci.

OUTLIER LOCI

Genome locations (or markers or base pairs) that show behaviour or patterns of variation that are extremely divergent from the rest of the genome (locus-specific effects), as revealed by simulations or statistical tests.

SELECTION SIGNATURE

The molecular footprint of a selection event from the recent past (for example, an excess of rare alleles at a locus relative to the abundance of rare alleles at loci across the rest of the genome).

POPULATION PARAMETERS

Parameters that characterize populations such as gene flow, migration rates, effective size, change in size, relatedness and phylogeny.

SELECTIVE SWEEP

The increase in frequency of an allele (and closely linked chromosomal segments) that is caused by selection for the allele. Sweeps initially reduce variation and subsequently lead to a local excess of rare alleles (homozygosity excess) as new unique mutations accumulate.

AMPLIFIED FRAGMENT LENGTH POLYMORPHISM

(AFLP). A DNA fragment-length polymorphism that is revealed by a PCR-based DNA fingerprinting technique that generates dozens of polymorphic marker bands (presence or absence of a restriction enzyme site) in a single gel lane. The marker bands are usually dominant in that we generally cannot see the difference between a heterozygote and homozygote.

EFFECTIVE POPULATION SIZE

(Ne). Roughly the number of breeding individuals that produce offspring that live to reproductive age. It influences the rate of loss of genetic variation, the efficiency of natural selection, and the accumulation of beneficial and deleterious mutations. It is frequently much smaller than the number of individuals in a population.

GENOME TYPING

The simultaneous genotyping of hundreds of loci from across the genome, which ideally includes mapped loci and different classes of loci such as allozymes, microsatellites and AFLPs, or synonymous (non-coding) and non-synonymous nucleotide polymorphisms.

SEMI-MODEL SPECIES

Species that are not as extensively studied as classical model systems such as mice, Arabidopsis and Drosophila, but for which large data sets and effective genomic tools are beginning to be developed.

EXPRESSED SEQUENCE TAGS

(ESTs). Short DNA sequences (several hundred base pairs) that are produced by reverse transcription of mRNA into DNA. ESTs are cDNAs that consist of exons and the sequences that flank exons. The sequencing of ESTs allows rapid identification ('tagging') of genes and can expedite DNA marker (SNP) development in coding genes.

COMPARATIVE ANCHOR-TAG SEQUENCES

(CATS). Exon sequences that are conserved across taxa allowing the design of primers that amplify in divergent species (for example, across mammal orders). CATS-like primers speed the discovery of SNPs (in exons or introns) and comparative genome mapping across taxa.

EXON-PRIMED INTRON-CROSSING PCR

(EPIC-PCR). EPIC primers are designed in conserved exons and amplify intron sequences that are generally more polymorphic than exons, which are therefore useful for the development of SNP or RFLP markers.

HAPLOTYPE BLOCKS

Long stretches (tens of megabases) along a chromosome that have low recombination rates (and relatively few haplotypes). Adjacent blocks are separated by recombination hot spots (short regions with high recombination rates).

HARDY–WEINBERG

A law or model in which allele and genotype frequencies will reach equilibrium in one generation and remain constant from generation to generation in large random-mating populations with no mutation, migration or selection.

HOMOZYGOSITY EXCESS

A higher Hardy–Weinberg equilibrium homozygosity than that which is expected in a population at mutation–drift equilibrium with the same observed number of alleles. This is not an excess of homozygotes (deviation from Hardy–Weinberg proportions).

SELECTION COEFFICIENTS

The average proportional reduction in fitness of one genotype relative to another owing to selection (designated by 's').

ADMIXED

(Hybridized). An admixed population contains hybrids or offspring of individuals originating from genetically divergent parental populations.

CLINE

A gradient of variation across space. It usually refers to increased differences among populations in the frequency of an allele or trait with increased geographic distance.

EMPIRICAL DISTRIBUTION

The distribution of a test statistic (for example, Fst or Fis) that is computed from observed data obtained from hundreds of loci sampled genome-wide.

NULL DISTRIBUTION

(Neutral distribution). The distribution (or range) of values across which we expect to observe the value of the test statistic if the null hypothesis is true (for example, neutrality). When conducting a standard t-test, t is the test statistic and the null distribution is the normal (Gaussian) distribution with t degrees of freedom.

SUMMARY STATISTIC

A parameter estimate (such as Fst or Fis) that quantifies attributes of the data sampled from a population of interest.

BAYESIAN

A framework of statistical inference in which previous beliefs (or data) and likelihoods are combined to estimate a parameter of interest given the observed data.

LIKELIHOOD-BASED TEST

Statistical tests that consider how likely the data are given an assumed model.

MARKOV CHAIN MONTE CARLO

(MCMC). A simulation-based computational technique for the numerical calculation of likelihoods.

MOLECULAR ADAPTATION

Genetic change (for example, allele frequency shift or amino-acid substitution) in response to natural selection.

PHYLOGEOGRAPHY

The study of the geographic distribution of phylogenetic lineages, usually within species and to reconstruct the origins and diffusion of lineages.

MORPHOTYPES

Distinctive phenotypes. Organisms that are classified together on the basis of similar physical features without knowledge of their genetic relationships.

COALESCENT

Relating to the mathematical and statistical properties of genealogies. A modelling framework in which two DNA sequence lineages converge in a common ancestral sequence, going backwards in time.

BOOTSTRAP

A statistical approach that is often used to generate confidence intervals (measures of variation) around parameter estimates in which the data are re-sampled repeatedly (with replacement) using computer Monte Carlo simulations.

TEST STATISTIC

The summary value (often a summary statistic) of a data set that is compared with a statistical distribution to determine whether the data set differs from that expected under a null hypothesis.

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Luikart, G., England, P., Tallmon, D. et al. The power and promise of population genomics: from genotyping to genome typing. Nat Rev Genet 4, 981–994 (2003). https://doi.org/10.1038/nrg1226

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