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  • Review Article
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Understanding the origin of species with genome-scale data: modelling gene flow

Key Points

  • One of the great debates in evolution is about how one species separates into two. The now classical allopatric speciation model has started to be questioned by recent findings that point to divergence in the presence of gene flow.

  • Gene flow is expected to reduce the overall levels of differentiation across the genome. Divergence in the face of gene flow results from the interaction of the opposing forces of gene flow and diversifying selection and the action of recombination.

  • Today, next-generation sequencing (NGS) technologies and assembly tools make it possible to obtain genome-scale data affordably from multiple individuals from closely related populations and/or species, offering the promise of disentangling the complex interplay between selection, gene flow and recombination.

  • One common approach to learn about divergence is to scan the genome using indicators of population differentiation, such as FST. Examples of statistics that are sensitive only to certain aspects of divergence include the ABBA and BABA test (D statistic) for detecting and estimating unidirectional admixture (introgression).

  • Isolation with migration models provide a general theoretical framework for studying speciation. Alternative modes of divergence can be described by alternative isolation with migration models, such as models with no gene flow, secondary contact and migration followed by isolation.

  • A full portrait of the divergence processes can be obtained via the likelihood of a given divergence model. Currently, there are two main families of likelihood-based approaches to studying divergence: allele frequency spectrum (AFS) and genealogy-based approaches.

  • One of the major limitations of current likelihood methods arises when trying to model intermediate levels of recombination explicitly, thus great advances in population genomic inference could be achieved with a comprehensive model of recombination and population divergence. These areas are already undergoing active research, especially in the quest for finding good approximations for the likelihoods of complex demographic models.

Abstract

As it becomes easier to sequence multiple genomes from closely related species, evolutionary biologists working on speciation are struggling to get the most out of very large population genomic data sets. Such data hold the potential to resolve long-standing questions in evolutionary biology about the role of gene exchange in species formation. In principle, the new population genomic data can be used to disentangle the conflicting roles of natural selection and gene flow during the divergence process. However, there are great challenges in taking full advantage of such data, especially with regard to including recombination in genetic models of the divergence process. Current data, models, methods and the potential pitfalls in using them will be considered here.

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Figure 1: Alternative modes of divergence.
Figure 2: Disentangling ancestral polymorphism from gene flow (ABBA and BABA test).
Figure 3: Allele frequency spectrum under alternative divergence models.
Figure 4: Distinguishing migration events based on linkage disequilibrium block structure.

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Acknowledgements

This work was supported by grants from the US National Science Foundation and the US National Institutes of Health to J.H.

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Correspondence to Jody Hey.

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Glossary

Single-nucleotide polymorphisms

(SNPs). Sites in the DNA in which there is variation across the genomes in a population, usually comprising two alleles that correspond to two different nucleotides.

Ascertainment bias

Systematic bias introduced by the sampling design (for example, criteria used to select individuals and/or genetic markers) that induces a nonrandom sample of observations.

Paired-end libraries

Sequencing from each end of the fragments in a library. The two sequenced ends are typically separated by a gap.

Sympatric speciation

The process of divergence between populations or species occupying the same geographical area and in presence of gene flow.

Diversifying selection

Natural selection acting towards different alleles (or phenotypes) being favoured in different regions within a single population or among multiple connected populations.

Neutral genes

Genes for which genetic patterns are mostly affected by mutation and demographic factors, such as genetic drift and migration.

Allopatric divergence

The process of divergence between populations or species that are geographically separated, in the absence of gene flow.

Linkage disequilibrium

(LD). The nonrandom association of alleles at different sites or loci.

Islands of differentiation

Genomic regions of elevated differentiation owing to the action of natural selection.

F ST

The proportion of the total genetic variability occurring among populations, typically used as a measure of the level of population genetic differentiation.

Island model

A model introduced by Sewall Wright to study population structure comprising multiple populations connected to each other through migration.

Metapopulation model

In the context of FST-based statistics, this is an idealized model in which several populations diverge without migration from a common ancestral gene pool (or metapopulation).

Nested island model

A hierarchical island model with groups of populations in which migration among populations within the same group is higher than among populations in different groups.

Gene trees

Bifurcating trees that represent the ancestral relationships of homologous haplotypes sampled from a single or multiple populations. A gene tree includes coalescent events and, in models with gene flow, migration events. A gene tree is characterized by a topology, branch lengths, coalescence times and migration times.

Bayesian statistics

Statistical framework in which the parameters of the models are treated as random variables, allowing expression of the probability of parameters, given the data; this is called the posterior. The posterior probability is obtained by Bayes' rule, and it is proportional to the likelihood times the prior.

Allele frequency spectrum

(AFS). A distribution of the counts of single-nucleotide polymorphisms with a given observed frequency in a single or multiple populations.

Genetic drift

Stochastic changes in gene frequency owing to finite size of populations, resulting from the random sampling of gametes from the parents at each generation.

Coalescent theory

A theory that describes the distribution of gene trees (and ancestral recombination graphs) under a given demographic model that can be used to compute the probability of a given gene tree.

Generating functions

Statistical technique used to obtain the distribution of sums of random variables, as required in computation of the probability of genealogies given the parameters of an underlying model.

Haplotype

A DNA sequence that is inherited as a single unit in the absence of recombination.

Bottlenecks

Reductions in the size of populations owing to stochastic events or owing to colonization of new areas (founder events).

Ancestral recombination graphs

(ARGs). Graphs that represent the ancestral relationship of homologous DNA sequences sampled from a single or multiple populations. In models with gene flow, an ARG includes coalescent, migration and recombination events.

Identity by descent

(IBD). Two haplotypes are identical by descent if they are identical copies of a haplotype that are shared between individuals within families and hence are assumed to be identical by descent.

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Sousa, V., Hey, J. Understanding the origin of species with genome-scale data: modelling gene flow. Nat Rev Genet 14, 404–414 (2013). https://doi.org/10.1038/nrg3446

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