Genomic signatures of parasite-driven natural selection in north European Atlantic salmon (Salmo salar)

Abstract Understanding the genomic basis of host-parasite adaptation is important for predicting the long-term viability of species and developing successful management practices. However, in wild populations, identifying specific signatures of parasite-driven selection often presents a challenge, as it is difficult to unravel the molecular signatures of selection driven by different, but correlated, environmental factors. Furthermore, separating parasite-mediated selection from similar signatures due to genetic drift and population history can also be difficult. Populations of Atlantic salmon (Salmo salar L.) from northern Europe have pronounced differences in their reactions to the parasitic flatworm Gyrodactylus salaris Malmberg 1957 and are therefore a good model to search for specific genomic regions underlying inter-population differences in pathogen response. We used a dense Atlantic salmon SNP array, along with extensive sampling of 43 salmon populations representing the two G. salaris response extremes (extreme susceptibility vs resistant), to screen the salmon genome for signatures of directional selection while attempting to separate the parasite effect from other factors. After combining the results from two independent genome scan analyses, 57 candidate genes potentially under positive selection were identified, out of which 50 were functionally annotated. This candidate gene set was shown to be functionally enriched for lymph node development, focal adhesion genes and anti-viral response, which suggests that the regulation of both innate and acquired immunity might be an important mechanism for salmon response to G. salaris. Overall, our results offer insights into the apparently complex genetic basis of pathogen susceptibility in salmon and highlight methodological challenges for separating the effects of various environmental factors.Peer reviewe

Commencement Program, August (1966)

https://red.mnstate.edu/commencement/1105/thumbnail.jp

A Dense SNP-Based Linkage Map for Atlantic Salmon (Salmo salar) Reveals extended Chromosome Homeologies and Striking Differences in Sex-Specific Recombination Patterns

Background: The Atlantic salmon genome is in the process of returning to a diploid state after undergoing awhole genome duplication (WGD) event between 25 and100 million years ago. Existing data on the proportion ofparalogous sequence variants (PSVs), multisite variants (MSVs) and other types of complex sequence variationsuggest that the rediplodization phase is far from over. The aims of this study were to construct a high densitylinkage map for Atlantic salmon, to characterize the extent of rediploidization and to improve our understandingof genetic differences between sexes in this species.Results: A linkage map for Atlantic salmon comprising 29 chromosomes and 5650 single nucleotidepolymorphisms (SNPs) was constructed using genotyping data from 3297 fish belonging to 143 families. Of these,2696 SNPs were generated from ESTs or other gene associated sequences. Homeologous chromosomal regionswere identified through the mapping of duplicated SNPs and through the investigation of syntenic relationshipsbetween Atlantic salmon and the reference genome sequence of the threespine stickleback (Gasterosteusaculeatus). The sex-specific linkage maps spanned a total of 2402.3 cM in females and 1746.2 cM in males,highlighting a difference in sex specific recombination rate (1.38:1) which is much lower than previously reportedin Atlantic salmon. The sexes, however, displayed striking differences in the distribution of recombination siteswithin linkage groups, with males showing recombination strongly localized to telomeres.Conclusion: The map presented here represents a valuable resource for addressing important questions of interestto evolution (the process of re-diploidization), aquaculture and salmonid life history biology and not least as aresource to aid the assembly of the forthcoming Atlantic salmon reference genome sequence

SNP genotyping reveals substructuring in weakly differentiated populations of Atlantic cod (Gadus morhua) from diverse environments in the Baltic Sea

Atlantic cod (Gadus morhua) is one of the most important fish species in northern Europe for several reasons including its predator status in marine ecosystems, its historical role in fisheries, its potential in aquaculture and its strong public profile. However, due to over-exploitation in the North Atlantic and changes in the ecosystem, many cod populations have been reduced in size and genetic diversity. Cod populations in the Baltic Proper, Kattegat and North Sea have been analyzed using a species specific single nucleotide polymorphism (SNP) array. Using a subset of 8,706 SNPs, moderate genetic differences were found between subdivisions in three traditionally delineated cod management stocks: Kattegat, western and eastern Baltic. However, an FST measure of population differentiation based on allele frequencies from 588 outlier loci for 2 population groups, one including 5 western and the other 4 eastern Baltic populations, indicated high genetic differentiation. In this paper, differentiation has been demonstrated not only between, but also within western and eastern Baltic cod stocks for the first time, with salinity appearing to be the most important environmental factor influencing the maintenance of cod population divergence between the western and eastern Baltic Sea

Dissecting the loci underlying maturation timing in Atlantic salmon using haplotype and multi-SNP based association methods

Characterizing the role of different mutational effect sizes in the evolution of fitness-related traits has been a major goal in evolutionary biology for a century. Such characterization in a diversity of systems, both model and non-model, will help to understand the genetic processes underlying fitness variation. However, well-characterized genetic architectures of such traits in wild populations remain uncommon. In this study, we used haplotype-based and multi-SNP Bayesian association methods with sequencing data for 313 individuals from wild populations to test the mutational composition of known candidate regions for sea age at maturation in Atlantic salmon (Salmo salar). We detected an association at five loci out of 116 candidates previously identified in an aquaculture strain with maturation timing in wild Atlantic salmon. We found that at four of these five loci, variation explained by the locus was predominantly driven by a single SNP suggesting the genetic architecture of this trait includes multiple loci with simple, non-clustered alleles and a locus with potentially more complex alleles. This highlights the diversity of genetic architectures that can exist for fitness-related traits. Furthermore, this study provides a useful multi-SNP framework for future work using sequencing data to characterize genetic variation underlying phenotypes in wild populations.Peer reviewe

HUNK phosphorylates EGFR to regulate breast cancer metastasis

Epidermal growth factor receptor (EGFR) is commonly over-expressed in metastatic breast cancer yet metastatic breast cancer is generally resistant to anti-EGFR therapies, and the mechanism for resistance to EGFR inhibitors in this setting is not fully understood. Hormonally up-regulated neu-associated kinase (HUNK) kinase is up-regulated in aggressive breast cancers and is thought to play a role in breast cancer metastasis. However, no studies have been conducted to examine a relationship between EGFR and HUNK in breast cancer metastasis. We performed a kinase substrate screen and identified that EGFR is phosphorylated by HUNK. Our studies show that HUNK phosphorylates EGFR at T654, enhancing receptor stability and downstream signaling. We found that increased phosphorylation of T654 EGFR correlates with increased epithelial to mesenchymal, migration and invasion, and metastasis. In addition, we found that HUNK expression correlates with overall survival and distant metastasis free survival. This study shows that HUNK directly phosphorylates EGFR at T654 to promote metastasis and is the first study to show that the phosphorylation of this site in EGFR regulates metastasis

Identification of genomic regions regulating sex determination in Atlantic salmon using high density SNP data

Background: A complete understanding of the genetic basis for sexual determination and differentiation is necessary in order to implement efficient breeding schemes at early stages of development. Atlantic salmon belongs to the family Salmonidae of fishes and represents a species of great commercial value. Although the species is assumed to be male heterogametic with XY sex determination, the precise genetic basis of sexual development remains unclear. The complexity is likely associated to the relatively recent salmonid specific whole genome duplication that may be responsible for certain genome instability. This instability together with the capacity of the sex-determining gene to move across the genome as reported by previous studies, may explain that sexual development genes are not circumscribed to the same chromosomes in all members of the species. In this study, we have used a 220 K SNP panel developed for Atlantic salmon to identify the chromosomes explaining the highest proportion of the genetic variance for sex as well as candidate regions and genes associated to sexual development in this species. Results: Results from regional heritability analysis showed that the chromosomes explaining the highest proportion of variance in these populations were Ssa02 (heritability = 0.42, SE = 0.12) and Ssa21 (heritability = 0.26, SE = 0.11). After pruning by linkage disequilibrium, genome-wide association analyses revealed 114 SNPs that were significantly associated with sex, being Ssa02 the chromosome containing a greatest number of regions. Close examination of the candidate regions evidenced important genes related to sex in other species of Class Actinopterygii, including SDY, genes from family SOX, RSPO1, ESR1, U2AF2A, LMO7, GNRH-R, DND and FIGLA. Conclusions: The combined results from regional heritability analysis and genome-wide association have provided new advances in the knowledge of the genetic regulation of sex determination in Atlantic salmon, supporting that Ssa02 is the candidate chromosome for sex in this species and suggesting an alternative population lineage in Spanish wild populations according to the results from Ssa21.Ministerio de Economía y Competitividad | Ref. RZ2012–00011-C02–00Ministerio de Ciencia e Innovación | Ref. JCI-2011-1089

Optical modeling and polarization calibration for CMB measurements with ACTPol and Advanced ACTPol

The Atacama Cosmology Telescope Polarimeter (ACTPol) is a polarization sensitive upgrade to the Atacama Cosmology Telescope. Located at an elevation of 5190 m, ACTPol measures the Cosmic Microwave Background (CMB) temperature and polarization with arcminute-scale angular resolution. Calibration of the detector angles is a critical step in producing maps of the CMB polarization. Polarization angle offsets in the detector calibration can cause leakage in polarization from E to B modes and induce a spurious signal in the EB and TB cross correlations, which eliminates our ability to measure potential cosmological sources of EB and TB signals, such as cosmic birefringence. We present our optical modeling and measurements associated with calibrating the detector angles in ACTPol.Comment: 12 pages, 8 figures, conference proceedings submitted to Proceedings of SPIE; added reference in section 2 and merged repeated referenc