A supergene-linked estrogen receptor drives alternative phenotypes in a polymorphic songbird

Merritt, Jennifer R.; Grogan, Kathleen E.; Zinzow-Kramer, Wendy M.; Sun, Dan; Ortlund, Eric A.; Yi, Soojin V.; Maney, Donna L.

doi:10.1073/pnas.2011347117

Cited by 44 publications

(79 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Through suppressed recombination, inversions often form supergenes (Schwander et al, 2014), where certain allele combinations are fixed and evolve together. In some prominent examples of adaptive behavioral diversity, these supergenes have captured multiple loci involved in hormone signaling and metabolism (Merritt et al, 2018(Merritt et al, , 2020Horton et al, 2020). Steroid hormones often have widespread pleiotropic effects and modulate gene expression genome-wide across many different tissues (Beato, 1993).…”

Section: Introductionmentioning

confidence: 99%

Gene Expression Modification by an Autosomal Inversion Associated With Three Male Mating Morphs

2021

View full text Add to dashboard Cite

Chromosomal inversions are structural rearrangements that frequently provide genomic substrate for phenotypic diversity. In the ruff Philomachus pugnax, three distinct male reproductive morphs (Independents, Satellites and Faeders) are genetically determined by a 4.5 Mb autosomal inversion. Here we test how this stable inversion polymorphism affects gene expression in males during the lekking season. Gene expression may be altered through disruptions at the breakpoints and the accumulation of mutations due to suppressed recombination. We used quantitative PCR to measure expression of 11 candidate inversion genes across three different tissues (liver, adrenal glands and gonads) and tested for allelic imbalance in four inversion genes across 12 males of all three morphs (8 Independents, 2 Satellites, 2 Faeders). We quantified transcripts of CENPN, an essential gene disrupted by the inversion at the proximal breakpoint, at different exons distributed near and across the breakpoint region. Consistent with dosage dependent gene expression for the breakpoint gene CENPN, we found that expression in Independents was broadly similar for transcripts segments from inside and outside the inversion regions, whereas for Satellites and Faeders, transcript segments outside of the inversion showed at least twofold higher expression than those spanning over the breakpoint. Within the inversion, observed expression differences for inversion males across all four genes with allele-specific primers were consistent with allelic imbalance. We further analyzed gonadal expression of two inversion genes, HSD17B2 and SDR42E1, along with 12 non-inversion genes related to steroid metabolism and signaling in 25 males (13 Independents, 7 Satellites, 5 Faeders). Although we did not find clear morph differentiation for many individual genes, all three morphs could be separated based on gene expression differences when using linear discriminant analysis (LDA), regardless of genomic location (i.e., inside or outside of the inversion). This was robust to the removal of genes with the highest loadings. Pairwise correlations in the expression of genes showed significant correlations for 9–18 pairs of genes within morphs. However, between morphs, we only found a single association between genes SDR42E1 and AROM for Independents and Satellites. Our results suggest complex and wide-ranging changes in gene expression caused by structural variants.

show abstract

Section: Introductionmentioning

confidence: 99%

Gene Expression Modification by an Autosomal Inversion Associated With Three Male Mating Morphs

2021

View full text Add to dashboard Cite

show abstract

“…Specifically, Sun and colleagues show that extremely hypomethylated loci on the ZAL2 m allele are strongly enriched for TEs and that some ZAL2 m ‐encoded TEs are more highly expressed than TEs encoded on ZAL2. In contrast, large methylation differences between ZAL2 and ZAL2 m are strongly depleted in gene exons, consistent with selection to maintain the integrity of key genes within the supergene polymorphism (e.g., serotonin and estrogen receptors; Merritt et al, 2020; Tuttle et al, 2016).…”

Section: Figurementioning

confidence: 86%

“…Specifically, Sun and colleagues show that extremely hypomethylated loci on the ZAL2 m allele are strongly enriched for TEs and that some ZAL2 m -encoded TEs are more highly expressed than TEs encoded on ZAL2. In contrast, large methylation differences between ZAL2 and ZAL2 m are strongly depleted in gene exons, consistent with selection to maintain the integrity of key genes within the supergene polymorphism (e.g., serotonin and estrogen receptors;Merritt et al, 2020;Tuttle et al, 2016).Sun et al also tackle a perennial challenge in ecological epigenomics: interpreting the functional consequences of observed epigenetic variation. Indeed, while DNA methylation in gene promoters is negatively correlated with gene expression levels, this relationship tends to be weak genome-wide (Reynolds et al, 2014).…”

mentioning

confidence: 97%

Sparrows and supergenes: Ecological epigenetics in action

Anderson

Tung

2021

Molecular Ecology

View full text Add to dashboard Cite

Ecological epigenetics seeks to understand how naturally occurring epigenetic variation within and between species is related to ecologically relevant traits (Bossdorf et al., 2008). This relationship is important for understanding the mechanisms that govern phenotypic variation in natural populations, which arises in part via plasticity in gene regulation. For example, experimentally induced social competition in tree swallows leads to changes in DNA methylation in the brain, localized near genes involved in regulation of aggressive behaviour (Bentz et al., 2021). Epigenetic marks are also influenced by genetic variation, such that patterns of DNA methylation diverge in parallel with the genomes that they mark (Dubin et al., 2015).Case studies of genetic, epigenetic and gene regulatory co-evolution within natural animal populations remain rare, however-especially at loci that explain ecologically relevant trait variation.In this issue of Molecular Ecology, Sun et al., (2021) address this gap by investigating divergence and diversity in DNA methylation levels in white-throated sparrows (Zonotrichia albicollis), a species that segregates for two naturally occurring morphs: a more aggressive white-striped morph and a less aggressive tan-striped morph

show abstract

“…Finally, complex trait variation has been found to underlie behavioural differences among white-striped and tan-striped morphs in White-throated sparrows (Merritt et al, 2020). Here again, a large inversion has resulted in a supergene with significant morphological and behavioural differences, however, the aggressiveness noted in the white-striped morph is monogenic (Merritt et al, 2020).…”

Section: Relating Structural Variants To Complex Traits Of Conservation Interestmentioning

confidence: 98%

“…In addition, a supergene resulting from an inversion has been found to determine mating strategy and morphology in the Eurasian ruff (Küpper et al, 2016), it is notable that this is likely a lethal recessive variant (Lamichhaney et al, 2016). Finally, complex trait variation has been found to underlie behavioural differences among white-striped and tan-striped morphs in White-throated sparrows (Merritt et al, 2020). Here again, a large inversion has resulted in a supergene with significant morphological and behavioural differences, however, the aggressiveness noted in the white-striped morph is monogenic (Merritt et al, 2020).…”

Section: Relating Structural Variants To Complex Traits Of Conservation Interestmentioning

confidence: 99%

Expanding the conservation genomics toolbox: incorporating structural variants to enhance genomic studies for species of conservation concern

Wold

Galla

Santure

et al. 2021

Preprint

View full text Add to dashboard Cite

Structural variants (SVs) are large rearrangements (> 50 bp) within the genome that impact the form and structure of chromosomes. As a result, SVs are a significant source of functional genomic diversity, i.e. variation at genomic regions underpinning phenotype differences, that can have large effects on individual and population fitness. While there are increasing opportunities to investigate functional genomic diversity in threatened species via single nucleotide polymorphism (SNP) datasets, SVs remain understudied despite their potential influence on complex traits of conservation interest. In this future-focused Opinion, we contend that characterizing SVs offers the conservation genomics community an exciting opportunity to complement SNP-based approaches to enhance species recovery. We identify three critical resources to characterize SVs de novo: 1) High-quality, contiguous, annotated reference genome(s); 2) Whole genome resequence data from representative individuals of the target species/populations; and 3) Well-curated metadata including pedigrees. We also leverage the existing literature–predominantly in human health, agriculture and eco-evol biology–to identify pangenomic approaches for readily characterizing SVs and consider how integrating these into the conservation genomics toolbox may transform the way we intensively manage some of the world’s most threatened species.

show abstract

A supergene-linked estrogen receptor drives alternative phenotypes in a polymorphic songbird

Cited by 44 publications

References 69 publications

Gene Expression Modification by an Autosomal Inversion Associated With Three Male Mating Morphs

Gene Expression Modification by an Autosomal Inversion Associated With Three Male Mating Morphs

Sparrows and supergenes: Ecological epigenetics in action

Expanding the conservation genomics toolbox: incorporating structural variants to enhance genomic studies for species of conservation concern

Contact Info

Product

Resources

About