Speciation, the evolution of reproductive isolation among populations, is continuous, complex, and involves multiple, interacting barriers. Until it is complete, the effects of this process vary along the genome and can lead to a heterogeneous genomic landscape with peaks and troughs of differentiation and divergence. When gene flow occurs during speciation, barriers restricting gene flow locally in the genome lead to patterns of heterogeneity. However, genomic heterogeneity can also be produced or modified by variation in factors such as background selection and selective sweeps, recombination and mutation rate variation, and heterogeneous gene density. Extracting the effects of gene flow, divergent selection and reproductive isolation from such modifying factors presents a major challenge to speciation genomics. We argue one of the principal aims of the field is to identify the barrier loci involved in limiting gene flow. We first summarize the expected signatures of selection at barrier loci, at the genomic regions linked to them and across the entire genome. We then discuss the modifying factors that complicate the interpretation of the observed genomic landscape. Finally, we end with a road map for future speciation research: a proposal for how to account for these modifying factors and to progress towards understanding the nature of barrier loci. Despite the difficulties of interpreting empirical data, we argue that the availability of promising technical and analytical methods will shed further light on the important roles that gene flow and divergent selection have in shaping the genomic landscape of speciation.

Inversions are structural mutations that reverse the sequence of a chromosome segment and reduce the effective rate of recombination in the heterozygous state. They play a major role in adaptation, as well as in other evolutionary processes such as speciation. Although inversions have been studied since the 1920s, they remain difficult to investigate because the reduced recombination conferred by them strengthens the effects of drift and hitchhiking, which in turn can obscure signatures of selection. Nonetheless, numerous inversions have been found to be under selection. Given recent advances in population genetic theory and empirical study, here we review how different mechanisms of selection affect the evolution of inversions. A key difference between inversions and other mutations, such as single nucleotide variants, is that the fitness of an inversion may be affected by a larger number of frequently interacting processes. This considerably complicates the analysis of the causes underlying the evolution of inversions. We discuss the extent to which these mechanisms can be disentangled, and by which approach.AbstractInversions often play key roles in adaptation and speciation, but the processes that direct their evolution are obscured by the characteristic that makes them so unique (reduced recombination between arrangements). In this review, we examine how different mechanisms can impact inversion evolution, weaving together both theoretical and empirical studies. We emphasize that most patterns are overdetermined (i.e. can be caused by multiple processes), but we highlight new technologies that provide a path forward towards disentangling these mechanisms.

Adaptive divergence and speciation may happen despite opposition by gene flow. Identifying the genomic basis underlying divergence with gene flow is a major task in evolutionary genomics. Most approaches (e.g., outlier scans) focus on genomic regions of high differentiation. However, not all genomic architectures potentially underlying divergence are expected to show extreme differentiation. Here, we develop an approach that combines hybrid zone analysis (i.e., focuses on spatial patterns of allele frequency change) with system‐specific simulations to identify loci inconsistent with neutral evolution. We apply this to a genome‐wide SNP set from an ideally suited study organism, the intertidal snail Littorina saxatilis, which shows primary divergence between ecotypes associated with different shore habitats. We detect many SNPs with clinal patterns, most of which are consistent with neutrality. Among non‐neutral SNPs, most are located within three large putative inversions differentiating ecotypes. Many non‐neutral SNPs show relatively low levels of differentiation. We discuss potential reasons for this pattern, including loose linkage to selected variants, polygenic adaptation and a component of balancing selection within populations (which may be expected for inversions). Our work is in line with theory predicting a role for inversions in divergence, and emphasizes that genomic regions contributing to divergence may not always be accessible with methods purely based on allele frequency differences. These conclusions call for approaches that take spatial patterns of allele frequency change into account in other systems.

Both classical and recent studies suggest that chromosomal inversion polymorphisms are important in adaptation and speciation. However, biases in discovery and reporting of inversions make it difficult to assess their prevalence and biological importance. Here, we use an approach based on linkage disequilibrium among markers genotyped for samples collected across a transect between contrasting habitats to detect chromosomal rearrangements de novo. We report 17 polymorphic rearrangements in a single locality for the coastal marine snail, Littorina saxatilis . Patterns of diversity in the field and of recombination in controlled crosses provide strong evidence that at least the majority of these rearrangements are inversions. Most show clinal changes in frequency between habitats, suggestive of divergent selection, but only one appears to be fixed for different arrangements in the two habitats. Consistent with widespread evidence for balancing selection on inversion polymorphisms, we argue that a combination of heterosis and divergent selection can explain the observed patterns and should be considered in other systems spanning environmental gradients.

Chromosomal rearrangements (CRs) have been known since almost the beginning of genetics. While an important role for CRs in speciation has been suggested, evidence primarily stems from theoretical and empirical studies focusing on the microevolutionary level (i.e., on taxon pairs where speciation is often incomplete). Although the role of CRs in eukaryotic speciation at a macroevolutionary level has been supported by associations between species diversity and rates of evolution of CRs across phylogenies, these findings are limited to a restricted range of CRs and taxa. Now that more broadly applicable and precise CR detection approaches have become available, we address the challenges in filling some of the conceptual and empirical gaps between micro- and macroevolutionary studies on the role of CRs in speciation. We synthesize what is known about the macroevolutionary impact of CRs and suggest new research avenues to overcome the pitfalls of previous studies to gain a more comprehensive understanding of the evolutionary significance of CRs in speciation across the tree of life.