Gene Regulation and Speciation Mack, Katya L; Nachman, Michael W
Trends in genetics,
01/2017, Letnik:
33, Številka:
1
Journal Article
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Understanding the genetic architecture of speciation is a major goal in evolutionary biology. Hybrid dysfunction is thought to arise most commonly through negative interactions between alleles at two ...or more loci. Divergence between interacting regulatory elements that affect gene expression (i.e., regulatory divergence) may be a common route for these negative interactions to arise. We review here how regulatory divergence between species can result in hybrid dysfunction, including recent theoretical support for this model. We then discuss the empirical evidence for regulatory divergence between species and evaluate evidence for misregulation as a source of hybrid dysfunction. Finally, we review unresolved questions in gene regulation as it pertains to speciation and point to areas that could benefit from future research.
One approach to understanding the process of speciation is to characterize the genetic architecture of post-zygotic isolation. As gene regulation requires interactions between loci, negative ...epistatic interactions between divergent regulatory elements might underlie hybrid incompatibilities and contribute to reproductive isolation. Here, we take advantage of a cross between house mouse subspecies, where hybrid dysfunction is largely unidirectional, to test several key predictions about regulatory divergence and reproductive isolation. Regulatory divergence between Mus musculus musculus and M. m. domesticus was characterized by studying allele-specific expression in fertile hybrid males using mRNA-sequencing of whole testes. We found extensive regulatory divergence between M. m. musculus and M. m. domesticus, largely attributable to cis-regulatory changes. When both cis and trans changes occurred, they were observed in opposition much more often than expected under a neutral model, providing strong evidence of widespread compensatory evolution. We also found evidence for lineage-specific positive selection on a subset of genes related to transcriptional regulation. Comparisons of fertile and sterile hybrid males identified a set of genes that were uniquely misexpressed in sterile individuals. Lastly, we discovered a nonrandom association between these genes and genes showing evidence of compensatory evolution, consistent with the idea that regulatory interactions might contribute to Dobzhansky-Muller incompatibilities and be important in speciation.
Identifying a common set of genes that mediate host–microbial interactions across populations and species of mammals has broad relevance for human health and animal biology. However, the genetic ...basis of the gut microbial composition in natural populations remains largely unknown outside of humans. Here, we used wild house mouse populations as a model system to ask three major questions: (a) Does host genetic relatedness explain interindividual variation in gut microbial composition? (b) Do population differences in the microbiota persist in a common environment? (c) What are the host genes associated with microbial richness and the relative abundance of bacterial genera? We found that host genetic distance is a strong predictor of the gut microbial composition as characterized by 16S amplicon sequencing. Using a common garden approach, we then identified differences in microbial composition between populations that persisted in a shared laboratory environment. Finally, we used exome sequencing to associate host genetic variants with microbial diversity and relative abundance of microbial taxa in wild mice. We identified 20 genes that were associated with microbial diversity or abundance including a macrophage‐derived cytokine (IL12a) that contained three nonsynonymous mutations. Surprisingly, we found a significant overrepresentation of candidate genes that were previously associated with microbial measurements in humans. The homologous genes that overlapped between wild mice and humans included genes that have been associated with traits related to host immunity and obesity in humans. Gene–bacteria associations identified in both humans and wild mice suggest some commonality to the host genetic determinants of gut microbial composition across mammals.
Natural history collections provide an immense record of biodiversity on Earth. These repositories have traditionally been used to address fundamental questions in biogeography, systematics and ...conservation. However, they also hold the potential for studying evolution directly. While some of the best direct observations of evolution have come from long‐term field studies or from experimental studies in the laboratory, natural history collections are providing new insights into evolutionary change in natural populations. By comparing phenotypic and genotypic changes in populations through time, natural history collections provide a window into evolutionary processes. Recent studies utilizing this approach have revealed some dramatic instances of phenotypic change over short timescales in response to presumably strong selective pressures. In some instances, evolutionary change can be paired with environmental change, providing a context for potential selective forces. Moreover, in a few cases, the genetic basis of phenotypic change is well understood, allowing for insight into adaptive change at multiple levels. These kinds of studies open the door to a wide range of previously intractable questions by enabling the study of evolution through time, analogous to experimental studies in the laboratory, but amenable to a diversity of species over longer timescales in natural populations.
House mice (Mus musculus) arrived in the Americas only recently in association with European colonization (~400-600 generations), but have spread rapidly and show evidence of local adaptation. Here, ...we take advantage of this genetic model system to investigate the genomic basis of environmental adaptation in house mice. First, we documented clinal patterns of phenotypic variation in 50 wild-caught mice from a latitudinal transect in Eastern North America. Next, we found that progeny of mice from different latitudes, raised in a common laboratory environment, displayed differences in a number of complex traits related to fitness. Consistent with Bergmann's rule, mice from higher latitudes were larger and fatter than mice from lower latitudes. They also built bigger nests and differed in aspects of blood chemistry related to metabolism. Then, combining exomic, genomic, and transcriptomic data, we identified specific candidate genes underlying adaptive variation. In particular, we defined a short list of genes with cis-eQTL that were identified as candidates in exomic and genomic analyses, all of which have known ties to phenotypes that vary among the studied populations. Thus, wild mice and the newly developed strains represent a valuable resource for future study of the links between genetic variation, phenotypic variation, and climate.
Changes in
-regulatory regions are thought to play a major role in the genetic basis of adaptation. However, few studies have linked
-regulatory variation with adaptation in natural populations. ...Here, using a combination of exome and RNA-seq data, we performed expression quantitative trait locus (eQTL) mapping and allele-specific expression analyses to study the genetic architecture of regulatory variation in wild house mice (
) using individuals from five populations collected along a latitudinal cline in eastern North America. Mice in this transect showed clinal patterns of variation in several traits, including body mass. Mice were larger in more northern latitudes, in accordance with Bergmann's rule. We identified 17 genes where
-eQTLs were clinal outliers and for which expression level was correlated with latitude. Among these clinal outliers, we identified two genes (
and
) with
-eQTLs that were associated with adaptive body mass variation and for which expression is correlated with body mass both within and between populations. Finally, we performed a weighted gene co-expression network analysis (WGCNA) to identify expression modules associated with measures of body size variation in these mice. These findings demonstrate the power of combining gene expression data with scans for selection to identify genes involved in adaptive phenotypic evolution, and also provide strong evidence for
-regulatory elements as essential loci of environmental adaptation in natural populations.
Circadian rhythms are nearly ubiquitous throughout nature, suggesting they are critical for survival in diverse environments. Organisms inhabiting largely arrhythmic environments, such as caves, ...offer a unique opportunity to study the evolution of circadian rhythms in response to changing ecological pressures. Populations of the Mexican tetra, Astyanax mexicanus, have repeatedly invaded caves from surface rivers, where individuals must contend with perpetual darkness, reduced food availability, and limited fluctuations in daily environmental cues. To investigate the molecular basis for evolved changes in circadian rhythms, we investigated rhythmic transcription across multiple independently-evolved cavefish populations. Our findings reveal that evolution in a cave environment has led to the repeated disruption of the endogenous biological clock, and its entrainment by light. The circadian transcriptome shows widespread reductions and losses of rhythmic transcription and changes to the timing of the activation/repression of core-transcriptional clock. In addition to dysregulation of the core clock, we find that rhythmic transcription of the melatonin regulator aanat2 and melatonin rhythms are disrupted in cavefish under darkness. Mutants of aanat2 and core clock gene rorca disrupt diurnal regulation of sleep in A. mexicanus, phenocopying circadian modulation of sleep and activity phenotypes of cave populations. Together, these findings reveal multiple independent mechanisms for loss of circadian rhythms in cavefish populations and provide a platform for studying how evolved changes in the biological clock can contribute to variation in sleep and circadian behavior.
Understanding how organisms adapt to new environments is a key problem in evolution, yet it remains unclear whether phenotypic plasticity generally facilitates or hinders this process. Here we ...studied evolved and plastic responses to water-stress in lab-born descendants of wild house mice (Mus musculus domesticus) collected from desert and non-desert environments and measured gene expression and organismal phenotypes under control and water-stressed conditions. After many generations in the lab, desert mice consumed significantly less water than mice from other localities, indicating that this difference has a genetic basis. Under water-stress, desert mice maintained more weight than non-desert mice, and exhibited differences in blood chemistry related to osmoregulatory function. Gene expression in the kidney revealed evolved differences between mice from different environments as well as plastic responses between hydrated and dehydrated mice. Desert mice showed reduced expression plasticity under water-stress compared to non-desert mice. Importantly, non-desert mice under water-stress generally showed shifts toward desertlike expression, consistent with adaptive plasticity. Finally, we identify several co-expression modules linked to phenotypes of interest. These findings provide evidence for local adaptation after a recent invasion and suggest that adaptive plasticity may have facilitated colonization of the desert environment.
Abstract
Cis-regulatory changes are thought to play a major role in adaptation. Threespine sticklebacks have repeatedly colonized freshwater habitats in the Northern Hemisphere, where they have ...evolved a suite of phenotypes that distinguish them from marine populations, including changes in physiology, behavior, and morphology. To understand the role of gene regulatory evolution in adaptive divergence, here we investigate cis-regulatory changes in gene expression between marine and freshwater ecotypes through allele-specific expression (ASE) in F1 hybrids. Surveying seven ecologically relevant tissues, including three sampled across two developmental stages, we identified cis-regulatory divergence affecting a third of genes, nearly half of which were tissue-specific. Next, we compared allele-specific expression in dental tissues at two timepoints to characterize cis-regulatory changes during development between marine and freshwater fish. Applying a genome-wide test for selection on cis-regulatory changes, we find evidence for lineage-specific selection on several processes between ecotypes, including the Wnt signaling pathway in dental tissues. Finally, we show that genes with ASE, particularly those that are tissue-specific, are strongly enriched in genomic regions of repeated marine-freshwater divergence, supporting an important role for these cis-regulatory differences in parallel adaptive evolution of sticklebacks to freshwater habitats. Altogether, our results provide insight into the cis-regulatory landscape of divergence between stickleback ecotypes across tissues and during development, and support a fundamental role for tissue-specific cis-regulatory changes in rapid adaptation to new environments.
Changes in gene expression are thought to play a major role in adaptive evolution. While it is known that gene expression is highly sensitive to the environment, very few studies have determined the ...influence of genetic and environmental effects on adaptive gene expression differences in natural populations. Here, we utilize allele-specific expression to characterize
cis
and
trans
gene regulatory divergence in temperate and tropical house mice in two metabolic tissues under two thermal conditions. First, we show that gene expression divergence is pervasive between populations and across thermal conditions, with roughly 5 to 10% of genes exhibiting genotype-by-environment interactions. Second, we found that most expression divergence was due to
cis
-regulatory changes that were stable across temperatures. In contrast, patterns of expression plasticity were largely attributable to
trans
-effects, which showed greater sensitivity to temperature. Nonetheless, we found a small subset of temperature-dependent
cis
-regulatory changes, thereby identifying loci underlying expression plasticity. Finally, we performed scans for selection in wild house mice to identify genomic signatures of rapid adaptation. Genomic outliers were enriched in genes with evidence for
cis
-regulatory divergence. Notably, these genes were associated with phenotypes that affected body weight and metabolism, suggesting that
cis-
regulatory changes are a possible mechanism for adaptive body size evolution between populations. Our results show that gene expression plasticity, largely controlled in
trans
, may facilitate the colonization of new environments, but that evolved changes in gene expression are largely controlled in
cis
, illustrating the genetic and nongenetic mechanisms underlying the establishment of populations in new environments.
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