Using neutral and outlier loci to uncover the genetic structure of 'Mytilus galloprovincialis' populations from the eastern Adriatic coast using population genetic and seascape genetic approaches

<p>The genetic variation of the Mediterranean blue mussel, Mytilus galloprovincialis from the eastern coastline of the Adriatic Sea was investigated using polymorphic microsatellite markers. In total, 843 individuals were sampled from 18 populations representing a variety of coastal environments in Croatia, Bosnia-Herzegovina, Montenegro and Albania. Neutral loci revealed low levels of genetic structure in this continuously distributed species, while one outlier locus, MGE7, which may be under selection, provided strong evidence of genetic structure. The distribution of one of the alleles of this locus, MGE7²⁴³, was significantly correlated with latitude. A genetic seascape analysis using 9 environmental and 3 geospatial variables revealed a strong association between MGE7²⁴³ and three highly correlated environmental variables, maximum sea surface temperature, minimum salinity and maximum chlorophyll-a. This association was maintained for homozygous genotypes for the MGE7²⁴³ allele, but not for heterozygotes, providing further evidence that the locus MGE7 may be under selection or closely linked to a gene under selection. These findings highlight how previously unrecognised genetic structure can be identified through the use of genetic seascape approaches.</p>

Using neutral and outlier loci to uncover the genetic structure of 'Mytilus galloprovincialis' populations from the eastern Adriatic coast using population genetic and seascape genetic approaches

<p>The genetic variation of the Mediterranean blue mussel, Mytilus galloprovincialis from the eastern coastline of the Adriatic Sea was investigated using polymorphic microsatellite markers. In total, 843 individuals were sampled from 18 populations representing a variety of coastal environments in Croatia, Bosnia-Herzegovina, Montenegro and Albania. Neutral loci revealed low levels of genetic structure in this continuously distributed species, while one outlier locus, MGE7, which may be under selection, provided strong evidence of genetic structure. The distribution of one of the alleles of this locus, MGE7²⁴³, was significantly correlated with latitude. A genetic seascape analysis using 9 environmental and 3 geospatial variables revealed a strong association between MGE7²⁴³ and three highly correlated environmental variables, maximum sea surface temperature, minimum salinity and maximum chlorophyll-a. This association was maintained for homozygous genotypes for the MGE7²⁴³ allele, but not for heterozygotes, providing further evidence that the locus MGE7 may be under selection or closely linked to a gene under selection. These findings highlight how previously unrecognised genetic structure can be identified through the use of genetic seascape approaches.</p>

Population structure and adaptive variation of Helichrysum italicum (Roth) G. Don along eastern Adriatic temperature and precipitation gradient

Immortelle (Helichrysum italicum (Roth) G. Don; Asteraceae) is a perennial plant species native to the Mediterranean region, known for many properties with wide application mainly in perfume and cosmetic industry. A total of 18 wild H. italicum populations systematically sampled along the eastern Adriatic environmental gradient were studied using AFLP markers to determine genetic diversity and structure and to identify loci potentially responsible for adaptive divergence. Results showed higher levels of intrapopulation diversity than interpopulation diversity. Genetic differentiation among populations was significant but low, indicating extensive gene flow between populations. Bayesian analysis of population structure revealed the existence of two genetic clusters. Combining the results of FST - outlier analysis (Mcheza and BayeScan) and genome-environment association analysis (Samβada, LFMM) four AFLP loci strongly associated with the bioclimatic variables Bio03 Isothermality, Bio08 Mean temperature of the wettest quarter, Bio15 Precipitation seasonality, and Bio17 Precipitation of driest quarter were found to be the main variables driving potential adaptive genetic variation in H. italicum along the eastern Adriatic environmental gradient. Redundancy analysis revealed that the partitioning of genetic variation was mainly associated with the adaptation to temperature oscillations. The results of the research may contribute to a clearer understanding of the importance of local adaptations for the genetic differentiation of Mediterranean plants and allow the planning of appropriate conservation strategies. However, considering that the identified outlier loci may be linked to genes under selection rather than being the target of natural selection, future studies must aim at their additional analysis.

ClineHelpR: an R package for genomic cline outlier detection and visualization

Background Patterns of multi-locus differentiation (i.e., genomic clines) often extend broadly across hybrid zones and their quantification can help diagnose how species boundaries are shaped by adaptive processes, both intrinsic and extrinsic. In this sense, the transitioning of loci across admixed individuals can be contrasted as a function of the genome-wide trend, in turn allowing an expansion of clinal theory across a much wider array of biodiversity. However, computational tools that serve to interpret and consequently visualize ‘genomic clines’ are limited, and users must often write custom, relatively complex code to do so. Results Here, we introduce the ClineHelpR R-package for visualizing genomic clines and detecting outlier loci using output generated by two popular software packages, bgc and Introgress. ClineHelpR bundles both input generation (i.e., filtering datasets and creating specialized file formats) and output processing (e.g., MCMC thinning and burn-in) with functions that directly facilitate interpretation and hypothesis testing. Tools are also provided for post-hoc analyses that interface with external packages such as ENMeval and RIdeogram. Conclusions Our package increases the reproducibility and accessibility of genomic cline methods, thus allowing an expanded user base and promoting these methods as mechanisms to address diverse evolutionary questions in both model and non-model organisms. Furthermore, the ClineHelpR extended functionality can evaluate genomic clines in the context of spatial and environmental features, allowing users to explore underlying processes potentially contributing to the observed patterns and helping facilitate effective conservation management strategies.

Selective sorting of ancestral introgression in maize and teosinte along an elevational cline

While often deleterious, hybridization can also be a key source of genetic variation and pre-adapted haplotypes, enabling rapid evolution and niche expansion. Here we evaluate these opposing selection forces on introgressed ancestry between maize (Zea mays ssp. mays) and its wild teosinte relative, mexicana (Zea mays ssp. mexicana). Introgression from ecologically diverse teosinte may have facilitated maize’s global range expansion, in particular to challenging high elevation regions (> 1500 m). We generated low-coverage genome sequencing data for 348 maize and mexicana individuals to evaluate patterns of introgression in 14 sympatric population pairs, spanning the elevational range of mexicana, a teosinte endemic to the mountains of Mexico. While recent hybrids are commonly observed in sympatric populations and mexicana demonstrates fine-scale local adaptation, we find that the majority of mexicana ancestry tracts introgressed into maize over 1000 generations ago. This mexicana ancestry seems to have maintained much of its diversity and likely came from a common ancestral source, rather than contemporary sympatric populations, resulting in relatively low FST between mexicana ancestry tracts sampled from geographically distant maize populations. Introgressed mexicana ancestry in maize is reduced in lower-recombination rate quintiles of the genome and around domestication genes, consistent with pervasive selection against introgression. However, we also find mexicana ancestry increases across the sampled elevational gradient and that high introgression peaks are most commonly shared among high-elevation maize populations, consistent with introgression from mexicana facilitating adaptation to the highland environment. In the other direction, we find patterns consistent with adaptive and clinal introgression of maize ancestry into sympatric mexicana at many loci across the genome, suggesting that maize also contributes to adaptation in mexicana, especially at the lower end of its elevational range. In sympatric maize, in addition to high introgression regions we find many genomic regions where selection for local adaptation maintains steep gradients in introgressed mexicana ancestry across elevation, including at least two inversions: the well-characterized 14 Mb Inv4m on chromosome 4 and a novel 3 Mb inversion Inv9f surrounding the macrohairless1 locus on chromosome 9. Most outlier loci with high mexicana introgression show no signals of sweeps or local sourcing from sympatric populations and so likely represent ancestral introgression sorted by selection, resulting in correlated but distinct outcomes of introgression in different contemporary maize populations.

Pan-cancer organoid validation of tumor outlier chromosomal amplification events

Somatic copy number gains are pervasive in many cancer types, yet their roles in oncogenesis are often poorly explored. This lack of understanding is in part due to broad extensions of copy gains across cancer genomes spanning large chromosomal regions, obscuring causal driver loci. Here we employed a multi-tissue pan-organoid modeling approach to validate candidate oncogenic loci identified within pan-cancer TCGA data by the overlap of extreme copy number amplifications with extreme expression dysregulation for each gene. The candidate outlier loci nominated by this integrative computational analysis were functionally validated by infecting cancer type-specific barcoded full length cDNA lentiviral libraries into cognate minimally transformed human and mouse organoids from the oral cavity, esophagus, colon, stomach, pancreas and lung. Presumptive amplification oncogenes were identified by barcode enrichment as a proxy for increased proliferation. Iterative analysis validated DYRK2 at 12q15, encoding a serine-threonine kinase, as an amplified head and neck squamous carcinoma oncogene in p53-/- oral mucosal organoids. Similarly, FGF3, amplified at 11q13 in 41% of esophageal squamous carcinomas, was validated in p53-/- esophageal organoids in vitro and in vivo with pharmacologic inhibition by small molecule and soluble receptor FGFR antagonists. Our studies establish the feasibility of pan-organoid contextual modeling of pan-cancer candidate genomic drivers, enabling oncogene discovery and preclinical therapeutic modeling.

Signatures of Adaptation and Acclimatization to Reef Flat and Slope Habitats in the Coral Pocillopora damicornis

Strong population-by-habitat interactions across environmental gradients arise from genetic adaptation or acclimatization and represents phenotypic variation required for populations to respond to changing environmental conditions. As such, patterns of adaptation and acclimatization of reef-building corals are integral to predictions of the future of coral reefs under climate warming. The common brooding coral, Pocillopora damicornis, exhibits extensive differences in host genetic and microbial symbiont community composition between depth habitats at Heron Island in the southern Great Barrier Reef, Australia. An 18-month reciprocal field transplant experiment was undertaken to examine the environmental and genetic drivers behind variation in survival, weight gain, heat tolerance and algal symbiont community between the reef flat and slope habitats. We observed population-by-habitat interactions for in situ partial mortality and weight gain, where trait-related fitness of natives was greater than transplants in most cases, consistent with local adaptation. On average, flat colonies transplanted to the slope had a relatively low partial mortality but minimal weight gain, whereas slope colonies transplanted to the flat had relatively high partial mortality and average weight gain. Experimental heat tolerance was always higher in colonies sourced from the flat, but increased when slope colonies were transplanted to the flat, providing evidence of acclimatization in these colonies. The performance of certain slope to flat transplants may have been driven by each colony’s algal symbiont (Symbiodiniaceae) community, and flat variants were observed in a small number of slope colonies that either had a fixed flat composition before transplantation or shuffled after transplantation. Host genotypes of previously identified genetic outlier loci could not predict survival following transplantation, possibly because of low sample size and/or polygenic basis to the traits examined. Local environmental conditions and Symbiodiniaceae composition may provide insight into the adaptive potential to changing environmental conditions.

Sardines at a junction: seascape genomics reveals ecological and oceanographic drivers of variation in the NW Mediterranean Sea

By evaluating genetic variation across the entire genome, one can address existing questions in a novel way while new can be asked. Such questions include how different local environments influence both adaptive and neutral genomic variation within and among populations, providing insights not only into local adaptation of natural populations, but also into their responses to global change and the exploitation-induced evolution. Here, under a seascape genomic approach, ddRAD genomic data were used along with environmental information to uncover the underlying processes (migration, selection) shaping European sardines (Sardina pilchardus) of the Western Mediterranean and adjacent Atlantic waters. This information can be relevant to the (re)definition of fishery stocks, and their short-term adaptive potential. We found that studied sardine samples form two clusters, detected using both neutral and adaptive (outlier) loci suggesting that natural selection and local adaptation play a key role in driving genetic change among the Atlantic and the Mediterranean sardines. Temperature and especially the trend in the number of days with sea surface temperature (SST) above 19oC was crucial at all levels of population structuring with implications on species’ key biological processes, especially reproduction. Our findings provide evidence for a dynamic equilibrium where population structure is maintained by physical and biological factors under the opposing influences of migration and selection. Given its dynamic nature, such a system postulates a continuous monitoring under a seascape genomic approach that can benefit by incorporating a temporal as well as a more detailed spatial dimension.

Green, yellow or black? Genetic differentiation and adaptation signatures in a highly migratory marine turtle

Marine species may exhibit genetic structure accompanied by phenotypic differentiation related to adaptation despite their high mobility. Two shape-based morphotypes have been identified for the green turtle ( Chelonia mydas ) in the Pacific Ocean: the south-central/western or yellow turtle and north-central/eastern or black turtle. The genetic differentiation between these morphotypes and the adaptation of the black turtle to environmentally contrasting conditions of the eastern Pacific region has remained a mystery for decades. Here we addressed both questions using a reduced-representation genome approach (Dartseq; 9473 neutral SNPs) and identifying candidate outlier loci (67 outlier SNPs) of biological relevance between shape-based morphotypes from eight Pacific foraging grounds ( n = 158). Our results support genetic divergence between morphotypes, probably arising from strong natal homing behaviour. Genes and enriched biological functions linked to thermoregulation, hypoxia, melanism, morphogenesis, osmoregulation, diet and reproduction were found to be outliers for differentiation, providing evidence for adaptation of C. mydas to the eastern Pacific region and suggesting independent evolutionary trajectories of the shape-based morphotypes. Our findings support the evolutionary distinctness of the enigmatic black turtle and contribute to the adaptive research and conservation genomics of a long-lived and highly mobile vertebrate.

Seascape genomics reveals population structure and local adaptation in a widespread coral reef snail, Coralliophila violacea (Kiener, 1836)

Local adaptation to different environments may reinforce neutral evolutionary divergence, especially in populations in the periphery of a species' geographic range. Seascape genomics (high-throughput genomics coupled with ocean climate databases) facilitates the exploration of neutral and adaptive variation in concert, developing a clearer picture of processes driving local adaptation in marine populations. This study used a seascape genomics approach to test the relative roles of neutral and adaptive processes shaping population divergence of a widespread coral reef snail, Coralliophila violacea. We collected C. violacea from colonies of their coral host (Porites spp.) at ten locations spanning a large portion of their geographic range. We used RAD-seq to investigate possible local adaptation via genetic-environmental associations with five ocean climate variables. Four genetic partitions were concordant with regions previously observed in mtDNA (Indian Ocean, Coral Triangle, and Hawaiian Islands), with the addition of Vietnam and varying isolation and admixture levels. We identified outlier loci (FDR = 0.10, N = 72) among individual localities and between regions (FDR = 0.10, N = 34), suggesting that some loci are putatively under divergent selection. Association analyses showed that the two strongest drivers of local adaptation were the annual range and mean of sea surface temperature. Populations that experience lower sea surface temperatures at the periphery of C. violacea's geographic range drive these associations. Our results show that local adaptation to different environments likely reinforces neutral divergence, especially in peripheral populations.