SUMMARY A major challenge in biology is to understand the genetic basis of adaptation. One compelling idea is that groups of tightly linked genes (i.e. ‘supergenes’ [1, 2]) facilitate adaptation in suites of traits that determine fitness. Despite their likely importance, little is known about how alternate supergene alleles arise and become differentiated, nor their ultimate fate within species. Herein we address these questions by investigating the evolutionary history of a supergene in white-throated sparrows, Zonotrichia albicollis. This species comprises two morphs, tan and white, that differ in pigmentation and components of social behavior [3–5]. Morph is determined by alternative alleles at a balanced >100Mb inversion-based supergene, providing a unique system for studying gene-behavior relationships. Using over two decades of field data we document near-perfect disassortative mating among morphs, as well as the fitness consequences of rare assortative mating. We use de novo whole genome sequencing coupled with population- and phylo-genomic data, to show that alternate supergene alleles are highly divergent at over 1,000 genes, that these alleles originated prior to the split of Z. albicollis from its sister species, and may be polymorphic in Z. albicollis due to a past hybridization event. We provide evidence that the ‘white' allele may be degrading, similar to neo-Y/Wsex chromosomes. We further show that the ‘tan’ allele has surprisingly low levels of genetic diversity, yet does not show several canonical signatures of recurrent positive selection. We discuss these results in the context of the origin, molecular evolution, and possible fate of this remarkable polymorphism.

Among the many anthropogenic changes that impact humans and wildlife, one of the most pervasive but least understood is light pollution. Although detrimental physiological and behavioural effects resulting from exposure to light at night are widely appreciated, the impacts of light pollution on infectious disease risk have not been studied. Here, we demonstrate that artificial light at night (ALAN) extends the infectious-to-vector period of the house sparrow ( Passer domesticus ), an urban-dwelling avian reservoir host of West Nile virus (WNV). Sparrows exposed to ALAN maintained transmissible viral titres for 2 days longer than controls but did not experience greater WNV-induced mortality during this window. Transcriptionally, ALAN altered the expression of gene regulatory networks including key hubs (OASL, PLBD1 and TRAP1) and effector genes known to affect WNV dissemination (SOCS). Despite mounting anti-viral immune responses earlier, transcriptomic signatures indicated that ALAN-exposed individuals probably experienced pathogen-induced damage and immunopathology, potentially due to evasion of immune effectors. A simple mathematical modelling exercise indicated that ALAN-induced increases of host infectious-to-vector period could increase WNV outbreak potential by approximately 41%. ALAN probably affects other host and vector traits relevant to transmission, and additional research is needed to advise the management of zoonotic diseases in light-polluted areas.

Simian immunodeficiency virus (SIV) challenge of rhesus macaques (RMs) vaccinated with strain 68–1 Rhesus Cytomegalovirus (RhCMV) vectors expressing SIV proteins (RhCMV/SIV) results in a binary outcome: stringent control and subsequent clearance of highly pathogenic SIV in ~55% of vaccinated RMs with no protection in the remaining 45%. Although previous work indicates that unconventionally restricted, SIV-specific, effector-memory (EM)-biased CD8+ T cell responses are necessary for efficacy, the magnitude of these responses does not predict efficacy, and the basis of protection vs. non-protection in 68–1 RhCMV/SIV vector-vaccinated RMs has not been elucidated. Here, we report that 68–1 RhCMV/SIV vector administration strikingly alters the whole blood transcriptome of vaccinated RMs, with the sustained induction of specific immune-related pathways, including immune cell, toll-like receptor (TLR), inflammasome/cell death, and interleukin-15 (IL-15) signaling, significantly correlating with subsequent vaccine efficacy. Treatment of a separate RM cohort with IL-15 confirmed the central involvement of this cytokine in the protection signature, linking the major innate and adaptive immune gene expression networks that correlate with RhCMV/SIV vaccine efficacy. This change-from-baseline IL-15 response signature was also demonstrated to significantly correlate with vaccine efficacy in an independent validation cohort of vaccinated and challenged RMs. The differential IL-15 gene set response to vaccination strongly correlated with the pre-vaccination activity of this pathway, with reduced baseline expression of IL-15 response genes significantly correlating with higher vaccine-induced induction of IL-15 signaling and subsequent vaccine protection, suggesting that a robust de novo vaccine-induced IL-15 signaling response is needed to program vaccine efficacy. Thus, the RhCMV/SIV vaccine imparts a coordinated and persistent induction of innate and adaptive immune pathways featuring IL-15, a known regulator of CD8+ T cell function, that support the ability of vaccine-elicited unconventionally restricted CD8+ T cells to mediate protection against SIV challenge.

BackgroundTwo subspecies of zebra finch, Taeniopygia guttata castanotis and T. g. guttata are native to Australia and the Lesser Sunda Islands, respectively. The Australian subspecies has been domesticated and is now an important model system for research. Both the Lesser Sundan subspecies and domesticated Australian zebra finches have undergone population bottlenecks in their history, and previous analyses using neutral markers have reported reduced neutral genetic diversity in these populations. Here we characterize patterns of variation in the third exon of the highly variable major histocompatibility complex (MHC) class I α chain. As a benchmark for neutral divergence, we also report the first mitochondrial NADH dehydrogenase 2 (ND2) sequences in this important model system.ResultsDespite natural and human-mediated population bottlenecks, we find that high MHC class I polymorphism persists across all populations. As expected, we find higher levels of nucleotide diversity in the MHC locus relative to neutral loci, and strong evidence of positive selection acting on important residues forming the peptide-binding region (PBR). Clear population differentiation of MHC allele frequencies is also evident, and this may be due to adaptation to new habitats and associated pathogens and/or genetic drift. Whereas the MHC Class I locus shows broad haplotype sharing across populations, ND2 is the first locus surveyed to date to show reciprocal monophyly of the two subspecies.ConclusionsDespite genetic bottlenecks and genetic drift, all surveyed zebra finch populations have maintained high MHC Class I diversity. The diversity at the MHC Class I locus in the Lesser Sundan subspecies contrasts sharply with the lack of diversity in previously examined neutral loci, and may thus be a result of selection acting to maintain polymorphism. Given uncertainty in historical population demography, however, it is difficult to rule out neutral processes in maintaining the observed diversity. The surveyed populations also differ in MHC Class I allele frequencies, and future studies are needed to assess whether these changes result in functional immune differences.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-015-0546-3) contains supplementary material, which is available to authorized users.

West Nile virus (WNV) is a widespread arbovirus that imposes a significant cost to both human and wildlife health. WNV exists in a bird-mosquito transmission cycle in which passerine birds act as the primary reservoir host. As a public health concern, the mammalian immune response to WNV has been studied in detail. Little, however, is known about the avian immune response to WNV. Avian taxa show variable susceptibility to WNV and what drives this variation is unknown. Thus, to study the immune response to WNV in birds, we experimentally infected captive zebra finches (Taeniopygia guttata). Zebra finches provide a useful model, as like many natural avian hosts they are moderately susceptible to WNV and thus provide sufficient viremia to infect mosquitoes. We performed RNAseq in spleen tissue during peak viremia to provide an overview of the transcriptional response. In general, we find strong parallels with the mammalian immune response to WNV, including upregulation of five genes in the Rig-I-like receptor signalling pathway, and offer insights into avian-specific responses. Together with complementary immunological assays, we provide a model of the avian immune response to WNV and set the stage for future comparative studies among variably susceptible populations and species.

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Simian immunodeficiency virus (SIV) challenge of rhesus macaques (RMs) vaccinated with Rhesus Cytomegalovirus (RhCMV) vectors expressing SIV proteins (RhCMV/SIV) results in a binary outcome: stringent control and subsequent clearance of highly pathogenic SIV in ~55% of vaccinated RMs with no protection in the remaining 45%. Although previous work suggests that unconventionally restricted, SIV-specific, effector-memory (EM)-biased CD8+ T cell responses are necessary for efficacy, the magnitude of these responses does not predict efficacy, and the basis of protection vs. non-protection in RhCMV/SIV vector-vaccinated RMs has not been elucidated. Here, we report that RhCMV/SIV vector administration strikingly alters the whole blood transcriptome of vaccinated RMs, with the sustained induction of specific immune-related pathways, including non-canonical T cell receptor (TCR), toll-lie receptor (TLR), inflammasome/cell death, and interleukin-15 (IL-15) signaling, significantly predicting protection. The IL-15 gene expression signature was further evaluated in an independent RM IL-15 treatment cohort, revealing that in whole blood the response to IL-15 is inclusive of innate and adaptive immune gene expression networks that link with RhCMV/SIV vaccine efficacy. We also show that this IL-15 response signature similarly tracks with vaccine protection in an independent RhCMV/SIV vaccination/SIV challenge RM validation cohort. Thus, the RhCMV/SIV vaccine imparts a coordinated and persistent induction of innate and adaptive immune pathways featuring IL-15, a known regulator of CD8+ T cell function, that enable vaccine-elicited CD8+ T cells to mediate protection against highly pathogenic SIV challenge.Author SummarySIV insert-expressing vaccine vectors based on strain 68-1 RhCMV elicit robust, highly effector-memory-biased T cell responses that are associated with an unprecedented level of SIV control after challenge (replication arrest leading to clearance) in slightly over half of vaccinated monkeys. Since efficacy is not predicted by standard measures of immunogenicity, we used functional genomics analysis of RhCMV/SIV vaccinated monkeys with known challenge outcomes to identify immune correlates of protection. We found that arrest of viral replication after challenge significantly correlates with a vaccine-induced response to IL-15 that includes modulation of T cell, inflammation, TLR signaling, and cell death programming. These data suggest that RhCMV/SIV efficacy is not based on chance, but rather, results from a coordinated and sustained vaccine-mediated induction of innate and adaptive immune pathways featuring IL-15, a known regulator of CD8+ effector-memory T cell function, that enable vaccine-elicited CD8+ T cells to mediate efficacy.

Parents can have profound effects on offspring fitness. Little, however, is known about the mechanisms through which parental genetic variation influences offspring physiology in natural systems. White‐throated sparrows (Zonotrichia albicollis, WTSP) exist in two genetic morphs, tan and white, controlled by a large polymorphic supergene. Morphs mate disassortatively, resulting in two pair types: tan male × white female (T × W) pairs, which provide biparental care and white male × tan female (W × T) pairs, which provide female‐biased care. To investigate how parental composition impacts offspring, we performed RNA‐seq on whole blood of WTSP nestlings sampled from nests of both pair types. Parental pair type had a large effect on nestling gene expression, with 881 genes differentially expressed (DE) and seven correlated gene coexpression modules. The DE genes and modules expressed at higher levels in W × T nests with female‐biased parental care function in metabolism and stress‐related pathways resulting from the overrepresentation of proteolysis and stress‐response genes (e.g., SOD2, NR3C1). These results show that parental genotypes and/or associated behaviours influence nestling physiology, and highlight avenues of further research investigating the ultimate implications for the maintenance of this polymorphism. Nestlings also exhibited morph‐specific gene expression, with 92 differentially expressed genes, comprising immunity genes and genes encompassed by the supergene. Remarkably, we identified the same regulatory hub genes in these blood‐derived expression networks as were previously identified in adult WTSP brains (EPM2A, BPNT1, TAF5L). These hub genes were located within the supergene, highlighting the importance of this gene complex in structuring regulatory networks across diverse tissues.