The genetic architecture of local adaptation has been of central interest to evolutionary biologists since the modern synthesis. In addition to classic theory on the effect size of adaptive mutations by Fisher, Kimura and Orr, recent theory addresses the genetic architecture of local adaptation in the face of ongoing gene flow. This theory predicts that with substantial gene flow between populations local adaptation should proceed primarily through mutations of large effect or tightly linked clusters of smaller effect loci. In this study, we investigate the genetic architecture of divergence in flowering time, mating system‐related traits, and leaf shape between
Demographic noise, the change in the composition of a population due to random birth and death events, is an important driving force in evolution because it reduces the efficacy of natural selection. Demographic noise is typically thought to be set by the population size and the environment, but recent experiments with microbial range expansions have revealed substantial strain-level differences in demographic noise under the same growth conditions. Many genetic and phenotypic differences exist between strains; to what extent do single mutations change the strength of demographic noise? To investigate this question, we developed a high-throughput method for measuring demographic noise in colonies without the need for genetic manipulation. By applying this method to 191 randomly-selected single gene deletion strains from the E. coli Keio collection, we find that a typical single gene deletion mutation decreases demographic noise by 8% (maximal decrease: 81%). We find that the strength of demographic noise is an emergent trait at the population level that can be predicted by colony-level traits but not cell-level traits. The observed differences in demographic noise from single gene deletions can increase the establishment probability of beneficial mutations by almost an order of magnitude (compared to in the wild type). Our results show that single mutations can substantially alter adaptation through their effects on demographic noise and suggest that demographic noise can be an evolvable trait of a population.
more » « less- NSF-PAR ID:
- 10218252
- Publisher / Repository:
- Oxford University Press
- Date Published:
- Journal Name:
- The ISME Journal
- Volume:
- 15
- Issue:
- 9
- ISSN:
- 1751-7362
- Format(s):
- Medium: X Size: p. 2643-2654
- Size(s):
- ["p. 2643-2654"]
- Sponsoring Org:
- National Science Foundation
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Abstract Mimulus laciniatus and a sympatric population of its close relativeM. guttatus . These three traits are probably involved inM. laciniatus’ adaptation to a dry, exposed granite outcrop environment. Flowering time and mating system differences are also reproductive isolating barriers making them ‘magic traits’. Phenotypic hybrids in this population provide evidence of recent gene flow. Using next‐generation sequencing, we generate denseSNP markers across the genome and map quantitative trait loci (QTL s) involved in flowering time, flower size and leaf shape. We find that interspecific divergence in all three traits is due to fewQTL of large effect including a highly pleiotropicQTL on chromosome 8. ThisQTL region contains the pleiotropic candidate gene TCP4 and is involved in ecologically important phenotypes in otherMimulus species. Our results are consistent with theory, indicating that local adaptation and reproductive isolation with gene flow should be due to few loci with large and pleiotropic effects. -
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Abstract Inbred populations often suffer from increased mutational load and reduced fitness due to lower efficacy of purifying selection in groups with small effective population sizes. Genetic rescue (GR) is a conservation tool that is studied and deployed with the aim of increasing the fitness of such inbred populations by assisted migration of individuals from closely related outbred populations. The success of GR depends on several factors—such as their demographic history and distribution of dominance effects of mutations—that may vary across populations. While we understand the impact of these factors on the dynamics of GR, their impact on local adaptations remains unclear. To this end, we conduct a population genetics simulation study to evaluate the impact of trait complexity (Mendelian vs. polygenic), dominance effects, and demographic history on the efficacy of GR. We find that the impact on local adaptations depends highly on the mutational load at the time of GR, which is in turn shaped dynamically by interactions between demographic history and dominance effects of deleterious variation. Over time local adaptations are generally restored post-GR, though in the short term they are often compromised in the process of purging deleterious variation. We also show that while local adaptations are almost always fully restored, the degree to which ancestral genetic variation affecting the trait is replaced by donor variation can vary drastically and is especially high for complex traits. Our results provide insights on the impact of GR on trait evolution and considerations for the practical implementation of GR.
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Abstract Phenotypic variation in organism-level traits has been studied in
Caenorhabditis elegans wild strains, but the impacts of differences in gene expression and the underlying regulatory mechanisms are largely unknown. Here, we use natural variation in gene expression to connect genetic variants to differences in organismal-level traits, including drug and toxicant responses. We perform transcriptomic analyses on 207 genetically distinctC. elegans wild strains to study natural regulatory variation of gene expression. Using this massive dataset, we perform genome-wide association mappings to investigate the genetic basis underlying gene expression variation and reveal complex genetic architectures. We find a large collection of hotspots enriched for expression quantitative trait loci across the genome. We further use mediation analysis to understand how gene expression variation could underlie organism-level phenotypic variation for a variety of complex traits. These results reveal the natural diversity in gene expression and possible regulatory mechanisms in this keystone model organism, highlighting the promise of using gene expression variation to understand how phenotypic diversity is generated. -
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Abstract Numerous organismal traits, particularly at the cellular level, are likely to be under persistent directional selection across phylogenetic lineages. Unless all mutations affecting such traits have large enough effects to be efficiently selected in all species, gradients in mean phenotypes are expected to arise as a consequence of differences in the power of random genetic drift, which varies by approximately five orders of magnitude across the Tree of Life. Prior theoretical work examining the conditions under which such gradients can arise focused on the simple situation in which all genomic sites affecting the trait have identical and constant mutational effects. Here, we extend this theory to incorporate the more biologically realistic situation in which mutational effects on a trait differ among nucleotide sites. Pursuit of such modifications leads to the development of semi-analytic expressions for the ways in which selective interference arises via linkage effects in single-effects models, which then extend to more complex scenarios. The theory developed clarifies the conditions under which mutations of different selective effects mutually interfere with each others’ fixation and shows how variance in effects among sites can substantially modify and extend the expected scaling relationships between mean phenotypes and effective population sizes.
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Abstract Background Titinopathies are inherited muscular diseases triggered by genetic mutations in the titin gene. Muscular dystrophy with myositis ( mdm ) is one such disease caused by a LINE repeat insertion, leading to exon skipping and an 83-amino acid residue deletion in the N2A-PEVK region of mouse titin. This region has been implicated in a number of titin—titin ligand interactions, hence are important for myocyte signaling and health. Mice with this mdm mutation develop a severe and progressive muscle degeneration. The range of phenotypic differences observed in mdm mice shows that the deletion of this region induces a cascade of transcriptional changes extending to numerous signaling pathways affected by the titin filament. Previous research has focused on correlating phenotypic differences with muscle function in mdm mice. These studies have provided understanding of the downstream physiological effects resulting from the mdm mutation but only provide insights on processes that can be physiologically observed and measured. We used differential gene expression (DGE) to compare the transcriptomes of extensor digitorum longus (EDL), psoas and soleus muscles from wild-type and mdm mice to develop a deeper understand of these tissue-specific responses. Results The overall expression pattern observed shows a well-differentiated transcriptional signature in mdm muscles compared to wild type. Muscle-specific clusters observed within the mdm transcriptome highlight the level of variability of each muscle to the deletion. Differential gene expression and weighted gene co-expression network analysis showed a strong directional response in oxidative respiration-associated mitochondrial genes, which aligns with the poor shivering and non-shivering thermogenesis previously observed. Sln, which is a marker associated with shivering and non-shivering thermogenesis, showed the strongest expression change in fast-fibered muscles. No drastic changes in MYH expression levels were reported, which indicated an absence of major fiber-type switching events. Overall expression shifts in MYH isoforms, MARPs, and extracellular matrix associated genes demonstrated the transcriptional complexity associated with mdm mutation. The expression alterations in mitochondrial respiration and metabolism related genes in the mdm muscle dominated over other transcriptomic changes, and likely account for the late stage cellular responses in the mdm muscles. Conclusions We were able to demonstrate that the complex nature of mdm mutation extends beyond a simple rearrangement in titin gene. EDL, psoas and soleus exemplify unique response modes observed in skeletal muscles with mdm mutation. Our data also raises the possibility that failure to maintain proper energy homeostasis in mdm muscles may contribute to the pathogenesis of the degenerative phenotype in mdm mice. Understanding the full disease-causing molecular cascade is difficult using bulk RNA sequencing techniques due to intricate nature of the disease. The development of the mdm phenotype is temporally and spatially regulated, hence future studies should focus on single fiber level investigations.more » « less
