PerspectiveEvolution

How many genetic changes create new species?

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Science  19 Feb 2021:
Vol. 371, Issue 6531, pp. 777-779
DOI: 10.1126/science.abf6671

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A genetic region that controls coloration generates morphs of Midas cichlid fish, but speciation involves traits controlled by a number of different genes.

PHOTO: AD KONINGS

The formation of new species generates biodiversity and is often driven by evolution through natural selection. However, the number of genetic changes involved in speciation is largely unknown. Many theoretical models predict that if speciation occurs without geographic isolation, it will be driven by a small number of genes. The logic is that only the few genes that experience the strongest natural selection can overcome the homogenizing effect of genetic mixing (i.e., gene flow) to diverge between populations. However, empirical studies in plants and animals now suggest that speciation—even with gene flow—involves differentiation in surprisingly many genetic regions. This is thought possible because the effects of selection can become coupled across correlated genes such that the selection each gene experiences is much stronger than it would receive in isolation. Thus, the potential for genes to evolve collectively because of coupling may be a key to understanding speciation.

Over recent decades, major strides have been made in understanding the speciation process, which is characterized by the evolution of reproductive isolation (i.e., barriers to interbreeding) and eventually widespread differentiation across the genome. For example, it is now known that natural selection often drives speciation (1). Moreover, it has been shown that selection can stem from the ecological environment, as proposed by Darwin, or can occur within genomes through conflict and competition between genetic elements.

In contrast to improved knowledge of the role of selection in speciation, the genetic changes involved are less understood (1). Filling this gap in understanding is important because genetic details, such as the number of genes affected by selection and their genomic organization, can influence the dynamics by which new species form (2, 3). For example, if only a few genes that are found together on the same chromosome drive speciation, the process could be highly constrained. By contrast, if many different genes and types of genetic changes drive speciation, the process may be more flexible, but less predictable (3). Although specific forms of reproductive isolation are known to be controlled by many genes, the overall genome-wide architecture of differentiation during the active phases of speciation remains poorly understood (1).

A key consideration is whether geographic factors allow interbreeding between diverging populations (i.e., gene flow) (25). When divergence occurs with strong geographic isolation—for example between mountain ranges—independent populations can readily diverge in many genetic regions by the combination of natural selection and chance. The situation with gene flow is different. This is because gene flow acts as a homogenizing force that mixes genes between populations, keeping them similar and preventing them from diverging into separate species. For speciation to occur, natural selection must act in contrasting directions in different populations, to oppose this mixing effect and generate differences. Amounts of gene flow, and thus the selection required to counter them, form a continuum ranging from absent or low to high and can vary over time and space during the speciation process.

Theoretical models predict that speciation with high gene flow is promoted by concentrated genetic architectures comprising one or few genes of large effect (24). This allows these few genes to experience strong natural selection to overcome gene flow. That is, selection needs to be concentrated on a few regions, rather than being spread thin among many genes. For example, with a gene flow rate of 0.10 (10% of individuals are immigrants), divergence occurs more readily if two genes each experience a selection intensity of 0.20 each (20% difference in expected fitness, higher than the gene flow rate) than if 10 genes experience an intensity of 0.04 (weaker than gene flow). The total selection intensity of 0.40 is the same in these two cases, but per gene, selection is stronger than gene flow only in the former (5). Thus, models and some findings have led to the concept that speciation with gene flow is driven by a few, isolated genomic islands of divergence. The remainder of the genome is overwhelmed by gene flow and cannot diverge.

In contrast to these theoretical predictions, emerging data suggest that speciation with gene flow can involve many genetic regions. For example, population differentiation and reproductive isolation based on numerous regions across the genome have now been reported in systems diverging with gene flow, including insects (e.g., Anopheles mosquitoes, Rhagoletis flies, Timema stick insects) (68), fish (cichlids and stickleback) (9, 10), and plants (sunflowers) (11), among others. Moreover, when divergence does occur in few genetic regions, this is often associated with discrete phenotypic morphs (as in mimetic butterflies) (12), rather than the strong reproductive isolation and genome-wide differentiation that characterize distinct species. In some cases, different outcomes have even been tied to variation in the genetic architecture of diverging traits. For example, differentiation in a genetic region controlling coloration generates morphs of Midas cichlid fish, but speciation and stable genome-wide differentiation involve traits controlled by a greater number of genes, such as jaw morphology and body shape (9). Thus, divergence in polygenic traits and multiple genetic regions seems key to progress toward speciation in some systems (see the figure).

Genetic changes that differentiate morphs and species

Patterns illustrate when few versus many genetic regions differentiate taxa. Black lines above the x axis represent two different chromosomes; the y axis represents the strength of genotype-phenotype association or the degree of population-genetic differentiation, represented by the orange traces.

GRAPHIC: N. DESAI/SCIENCE

Given that models predict that speciation with gene flow will involve few genes, can these recent empirical findings be reconciled with theory? The answer is yes, but this requires a look at a different body of theory, focused on geographic clines, which describes how allele frequencies change over space. This theory was largely developed in the 1980s by Nick Barton and colleagues to understand the dynamics of hybrid zones between species (13). The models show how statistical associations between different genetic regions (called “linkage disequilibrium”) can cause selection on one genetic region to be transferred to other correlated genetic regions. In essence, selection spills over, through association, from one genetic region to others. In this manner, the effects of selection can spread and become coupled across the genome, rather than being isolated to single genes (4, 13). Such coupling means that the total selection that each genetic region experiences is much stronger than the direct selection it experiences in isolation. Thus, numerous genetic regions can evolve collectively as a unit to overcome gene flow (4).

Notably, the geographic configuration of populations can change during the speciation process, as species ranges expand and contract over time. This means that gene flow itself can be dynamic and change over time. Rather than occurring entirely in the presence or absence of gene flow, speciation likely involves periods of each. In turn, this can result in episodic hybridization, with diverse implications for evolution. For example, periods of geographic isolation might allow a pool of standing genetic variation to build up, including in structural features such as chromosomal inversions, which kick-starts the coupling process and later aids divergence with gene flow (4, 14). Moreover, occasional bouts of gene flow can play a creative role in evolution by allowing for introgression of genes that facilitate adaptation, as reported in tropical butterflies (12), cichlids (14), sunflowers (11), and Darwin's finches (15). Thus, gene flow can have creative as well as homogenizing effects, and speciation likely reflects a balance between these effects.

Ideas concerning few versus many genes driving speciation are not in conflict. This is exemplified by Helianthus sunflowers (11) and Rhagoletis flies (7). In both systems, differentiation occurs genome-wide on many chromosomes but is accentuated in regions of reduced recombination, such as those harboring inversions. Thus, even with widespread genomic differentiation, by no means do all genetic regions always diverge equally; those under strong selection or experiencing low recombination may diverge more readily. Moreover, interactions between genes can amplify how strongly genes cause reproductive isolation, again making some genes more critical for speciation than others. Indeed, even speciation involving many genetic regions likely involves a finite number of building blocks, which can be combined in different ways to create diversity, as reported in sunflowers (11) and cichlids (14).

Despite this emerging evidence for the potential importance of genomic coupling in speciation, much work remains to be done. For example, almost all studies to date are purely correlational and often not highly replicated. Thus, experiments are needed to test causal effects of differentiated regions on reproductive isolation and coupling, as are larger studies examining numerous taxon pairs. Such experiments could comprise experimental evolution studies in the lab or field transplants in the wild. Moreover, natural history and molecular studies, including those using ancient DNA, are required to establish whether divergence really occurred with gene flow. This is critical because false inference of gene flow could lead to erroneous evidence for coupling, because numerous genetic regions diverge between isolated populations through other processes (5). Moreover, genome assembly errors, particularly in regions of low recombination, could lead to a single genetic region being falsely inferred as multiple regions of differentiation. Nonetheless, initial evidence points to coupling as a consideration for understanding speciation. In turn, this suggests that sets of genes might exhibit emergent properties not seen by individual genes, implying the potential for sudden tipping points in the ability for selection to overcome gene flow (4).

By combining theory and data, evolutionary biologists are now poised to better understand how new species are created. A large part of this understanding will involve discovering how the effects of genes and phenotypes become coupled to cause a transition from polymorphism or geographic variation within species to genome-wide differences between distinct species. A major outstanding question is the extent to which the microevolutionary process of coupling can explain broader macroevolutionary patterns of biodiversity, as observed in radiations such as those in cichlid fish (9, 14).

References and Notes

Acknowledgments: The work was funded by a grant from the European Research Council (EE-Dynamics 770826, https://erc.europa.eu/) to P.N., from NSF (DEB-1638997) and the U.S. Department of Agriculture–National Institute of Food and Agriculture program (2015-67013-23289) to J.L.F., and from the NSF (DEB 1844941) to Z.G. We thank D. Schluter for ongoing discussions concerning evolutionary genetics.
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