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1.
BMC Biol ; 22(1): 14, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38273313

RESUMO

BACKGROUND: Mosquito borne viruses, such as dengue, Zika, yellow fever and Chikungunya, cause millions of infections every year. These viruses are mostly transmitted by two urban-adapted mosquito species, Aedes aegypti and Aedes albopictus. Although mechanistic understanding remains largely unknown, Aedes mosquitoes may have unique adaptations that lower the impact of viral infection. Recently, we reported the identification of an Aedes specific double-stranded RNA binding protein (dsRBP), named Loqs2, that is involved in the control of infection by dengue and Zika viruses in mosquitoes. Preliminary analyses suggested that the loqs2 gene is a paralog of loquacious (loqs) and r2d2, two co-factors of the RNA interference (RNAi) pathway, a major antiviral mechanism in insects. RESULTS: Here we analyzed the origin and evolution of loqs2. Our data suggest that loqs2 originated from two independent duplications of the first double-stranded RNA binding domain of loqs that occurred before the origin of the Aedes Stegomyia subgenus, around 31 million years ago. We show that the loqs2 gene is evolving under relaxed purifying selection at a faster pace than loqs, with evidence of neofunctionalization driven by positive selection. Accordingly, we observed that Loqs2 is localized mainly in the nucleus, different from R2D2 and both isoforms of Loqs that are cytoplasmic. In contrast to r2d2 and loqs, loqs2 expression is stage- and tissue-specific, restricted mostly to reproductive tissues in adult Ae. aegypti and Ae. albopictus. Transgenic mosquitoes engineered to express loqs2 ubiquitously undergo developmental arrest at larval stages that correlates with massive dysregulation of gene expression without major effects on microRNAs or other endogenous small RNAs, classically associated with RNA interference. CONCLUSIONS: Our results uncover the peculiar origin and neofunctionalization of loqs2 driven by positive selection. This study shows an example of unique adaptations in Aedes mosquitoes that could ultimately help explain their effectiveness as virus vectors.


Assuntos
Aedes , Dengue , Infecção por Zika virus , Zika virus , Animais , Aedes/genética , Proteínas de Transporte/genética , Mosquitos Vetores/genética , RNA de Cadeia Dupla/genética , RNA de Cadeia Dupla/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Zika virus/genética , Zika virus/metabolismo
2.
PLoS Biol ; 17(7): e3000391, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31339877

RESUMO

Speciation genomic studies aim to interpret patterns of genome-wide variation in light of the processes that give rise to new species. However, interpreting the genomic "landscape" of speciation is difficult, because many evolutionary processes can impact levels of variation. Facilitated by the first chromosome-level assembly for the group, we use whole-genome sequencing and simulations to shed light on the processes that have shaped the genomic landscape during a radiation of monkeyflowers. After inferring the phylogenetic relationships among the 9 taxa in this radiation, we show that highly similar diversity (π) and differentiation (FST) landscapes have emerged across the group. Variation in these landscapes was strongly predicted by the local density of functional elements and the recombination rate, suggesting that the landscapes have been shaped by widespread natural selection. Using the varying divergence times between pairs of taxa, we show that the correlations between FST and genome features arose almost immediately after a population split and have become stronger over time. Simulations of genomic landscape evolution suggest that background selection (BGS; i.e., selection against deleterious mutations) alone is too subtle to generate the observed patterns, but scenarios that involve positive selection and genetic incompatibilities are plausible alternative explanations. Finally, tests for introgression among these taxa reveal widespread evidence of heterogeneous selection against gene flow during this radiation. Combined with previous evidence for adaptation in this system, we conclude that the correlation in FST among these taxa informs us about the processes contributing to adaptation and speciation during a rapid radiation.


Assuntos
Fluxo Gênico , Variação Genética , Genoma de Planta/genética , Genômica/métodos , Mimulus/genética , Seleção Genética , Adaptação Fisiológica/genética , Especiação Genética , Genética Populacional/métodos , Mimulus/classificação , Filogenia
3.
Genetics ; 226(4)2024 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-38242701

RESUMO

For at least the past 5 decades, population genetics, as a field, has worked to describe the precise balance of forces that shape patterns of variation in genomes. The problem is challenging because modeling the interactions between evolutionary processes is difficult, and different processes can impact genetic variation in similar ways. In this paper, we describe how diversity and divergence between closely related species change with time, using correlations between landscapes of genetic variation as a tool to understand the interplay between evolutionary processes. We find strong correlations between landscapes of diversity and divergence in a well-sampled set of great ape genomes, and explore how various processes such as incomplete lineage sorting, mutation rate variation, GC-biased gene conversion and selection contribute to these correlations. Through highly realistic, chromosome-scale, forward-in-time simulations, we show that the landscapes of diversity and divergence in the great apes are too well correlated to be explained via strictly neutral processes alone. Our best fitting simulation includes both deleterious and beneficial mutations in functional portions of the genome, in which 9% of fixations within those regions is driven by positive selection. This study provides a framework for modeling genetic variation in closely related species, an approach which can shed light on the complex balance of forces that have shaped genetic variation.


Assuntos
Variação Genética , Hominidae , Animais , Seleção Genética , Hominidae/genética , Mutação , Genômica
4.
bioRxiv ; 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36798346

RESUMO

For at least the past five decades population genetics, as a field, has worked to describe the precise balance of forces that shape patterns of variation in genomes. The problem is challenging because modelling the interactions between evolutionary processes is difficult, and different processes can impact genetic variation in similar ways. In this paper, we describe how diversity and divergence between closely related species change with time, using correlations between landscapes of genetic variation as a tool to understand the interplay between evolutionary processes. We find strong correlations between landscapes of diversity and divergence in a well sampled set of great ape genomes, and explore how various processes such as incomplete lineage sorting, mutation rate variation, GC-biased gene conversion and selection contribute to these correlations. Through highly realistic, chromosome-scale, forward-in-time simulations we show that the landscapes of diversity and divergence in the great apes are too well correlated to be explained via strictly neutral processes alone. Our best fitting simulation includes both deleterious and beneficial mutations in functional portions of the genome, in which 9% of fixations within those regions is driven by positive selection. This study provides a framework for modelling genetic variation in closely related species, an approach which can shed light on the complex balance of forces that have shaped genetic variation.

5.
Elife ; 122023 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-37342968

RESUMO

Simulation is a key tool in population genetics for both methods development and empirical research, but producing simulations that recapitulate the main features of genomic datasets remains a major obstacle. Today, more realistic simulations are possible thanks to large increases in the quantity and quality of available genetic data, and the sophistication of inference and simulation software. However, implementing these simulations still requires substantial time and specialized knowledge. These challenges are especially pronounced for simulating genomes for species that are not well-studied, since it is not always clear what information is required to produce simulations with a level of realism sufficient to confidently answer a given question. The community-developed framework stdpopsim seeks to lower this barrier by facilitating the simulation of complex population genetic models using up-to-date information. The initial version of stdpopsim focused on establishing this framework using six well-characterized model species (Adrion et al., 2020). Here, we report on major improvements made in the new release of stdpopsim (version 0.2), which includes a significant expansion of the species catalog and substantial additions to simulation capabilities. Features added to improve the realism of the simulated genomes include non-crossover recombination and provision of species-specific genomic annotations. Through community-driven efforts, we expanded the number of species in the catalog more than threefold and broadened coverage across the tree of life. During the process of expanding the catalog, we have identified common sticking points and developed the best practices for setting up genome-scale simulations. We describe the input data required for generating a realistic simulation, suggest good practices for obtaining the relevant information from the literature, and discuss common pitfalls and major considerations. These improvements to stdpopsim aim to further promote the use of realistic whole-genome population genetic simulations, especially in non-model organisms, making them available, transparent, and accessible to everyone.


Assuntos
Genoma , Software , Simulação por Computador , Genética Populacional , Genômica
6.
Genetics ; 220(3)2022 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-34897427

RESUMO

Stochastic simulation is a key tool in population genetics, since the models involved are often analytically intractable and simulation is usually the only way of obtaining ground-truth data to evaluate inferences. Because of this, a large number of specialized simulation programs have been developed, each filling a particular niche, but with largely overlapping functionality and a substantial duplication of effort. Here, we introduce msprime version 1.0, which efficiently implements ancestry and mutation simulations based on the succinct tree sequence data structure and the tskit library. We summarize msprime's many features, and show that its performance is excellent, often many times faster and more memory efficient than specialized alternatives. These high-performance features have been thoroughly tested and validated, and built using a collaborative, open source development model, which reduces duplication of effort and promotes software quality via community engagement.


Assuntos
Algoritmos , Modelos Genéticos , Simulação por Computador , Genética Populacional , Mutação , Software
7.
Front Genet ; 12: 676218, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34326859

RESUMO

It is pressing to understand how animal populations evolve in response to climate change. We argue that new sequencing technologies and the use of historical samples are opening unprecedented opportunities to investigate genome-wide responses to changing environments. However, there are important challenges in interpreting the emerging findings. First, it is essential to differentiate genetic adaptation from phenotypic plasticity. Second, it is extremely difficult to map genotype, phenotype, and fitness. Third, neutral demographic processes and natural selection affect genetic variation in similar ways. We argue that Drosophila melanogaster, a classical model organism with decades of climate adaptation research, is uniquely suited to overcome most of these challenges. In the near future, long-term time series genome-wide datasets of D. melanogaster natural populations will provide exciting opportunities to study adaptation to recent climate change and will lay the groundwork for related research in non-model systems.

8.
Evolution ; 75(8): 2042-2054, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34184262

RESUMO

Spatial and seasonal variations in the environment are ubiquitous. Environmental heterogeneity can affect natural populations and lead to covariation between environment and allele frequencies. Drosophila melanogaster is known to harbor polymorphisms that change both with latitude and seasons. Identifying the role of selection in driving these changes is not trivial, because nonadaptive processes can cause similar patterns. Given the environment changes in similar ways across seasons and along the latitudinal gradient, one promising approach may be to look for parallelism between clinal and seasonal changes. Here, we test whether there is a genome-wide correlation between clinal and seasonal changes, and whether the pattern is consistent with selection. Allele frequency estimates were obtained from pooled samples from seven different locations along the east coast of the United States, and across seasons within Pennsylvania. We show that there is a genome-wide correlation between clinal and seasonal variations, which cannot be explained by linked selection alone. This pattern is stronger in genomic regions with higher functional content, consistent with natural selection. We derive a way to biologically interpret these correlations and show that around 3.7% of the common, autosomal variants could be under parallel seasonal and spatial selection. Our results highlight the contribution of natural selection in driving fluctuations in allele frequencies in natural fly populations and point to a shared genomic basis to climate adaptation that happens over space and time in D. melanogaster.


Assuntos
Drosophila melanogaster , Genética Populacional , Animais , Drosophila melanogaster/genética , Frequência do Gene , Variação Genética , Pennsylvania , Estações do Ano , Seleção Genética , Estados Unidos
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