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Natural and human-driven selection of a single non-coding body size variant in ancient and modern canids.

ABSTRACT: Domestic dogs (Canis lupus familiaris) are the most variable-sized mammalian species on Earth, displaying a 40-fold size difference between breeds.¹ Although dogs of variable size are found in the archeological record,^2-4 the most dramatic shifts in body size are the result of selection over the last two centuries, as dog breeders selected and propagated phenotypic extremes within closed breeding populations.⁵ Analyses of over 200 domestic breeds have identified approximately 20 body size genes regulating insulin processing, fatty acid metabolism, TGFβ signaling, and skeletal formation.^6-10 Of these, insulin-like growth factor 1 (IGF1) predominates, controlling approximately 15% of body size variation between breeds.⁸ The identification of a functional mutation associated with IGF1 has thus far proven elusive.⁶^,¹⁰^,¹¹ Here, to identify and elucidate the role of an ancestral IGF1 allele in the propagation of modern canids, we analyzed 1,431 genome sequences from 13 species, including both ancient and modern canids, thus allowing us to define the evolutionary history of both ancestral and derived alleles at this locus. We identified a single variant in an antisense long non-coding RNA (IGF1-AS) that interacts with the IGF1 gene, creating a duplex. While the derived mutation predominates in both modern gray wolves and large domestic breeds, the ancestral allele, which predisposes to small size, was common in small-sized breeds and smaller wild canids. Our analyses demonstrate that this major regulator of canid body size nearly vanished in Pleistocene wolves, before its recent resurgence resulting from human-imposed selection for small-sized breed dogs.

SUBMITTER: Plassais J

PROVIDER: S-EPMC8891063 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Natural and human-driven selection of a single non-coding body size variant in ancient and modern canids.

Plassais Jocelyn J vonHoldt Bridgett M BM Parker Heidi G HG Carmagnini Alberto A Dubos Nicolas N Papa Ilenia I Bevant Kevin K Derrien Thomas T Hennelly Lauren M LM Whitaker D Thad DT Harris Alex C AC Hogan Andrew N AN Huson Heather J HJ Zaibert Victor F VF Linderholm Anna A Haile James J Fest Thierry T Habib Bilal B Sacks Benjamin N BN Benecke Norbert N Outram Alan K AK Sablin Mikhail V MV Germonpré Mietje M Larson Greger G Frantz Laurent L Ostrander Elaine A EA

Current biology : CB 20220131 4

Domestic dogs (Canis lupus familiaris) are the most variable-sized mammalian species on Earth, displaying a 40-fold size difference between breeds.1 Although dogs of variable size are found in the archeological record,2-4 the most dramatic shifts in body size are the result of selection over the last two centuries, as dog breeders selected and propagated phenotypic extremes within closed breeding populations.5 Analyses of over 200 domestic breeds have identified ...[more]

PMID: 35090588

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Project description:BackgroundAntimicrobial resistance presents a formidable challenge, yet its existence predates the introduction of antibiotics. Our study delves into the presence of antimicrobial resistance genes (ARGs) in ancient permafrost microbiomes, comparing them with contemporary soil and pristine environments. Majority of the samples are from regions around Beringia, encompassing parts of Russia and Alaska, with only one sample originating from the Tien Shan Mountain range in Kyrgyzstan.ResultsFrom over 2.3 tera basepairs of raw metagenomic data, retrieved from samples ranging in age from approximately 7,000 years to 1.1 million years, we assembled about 1.3 billion metagenomic contigs and explored the prevalence of ARGs within them. Our findings reveal a diverse array of ARGs in ancient microbiomes, akin to contemporary counterparts. On average, we identified 2 ARGs per rRNA gene in ancient samples. Actinomycetota, Bacillota, and several thermophiles were prominent carriers of ARGs in Chukochi and Kamchatkan samples. Conversely, ancient permafrost from the Tien Shan Mountain range exhibited no Thermophiles or Actinomycetota carrying ARGs. Both ancient and contemporary microbiomes showcased numerous divergent ARGs, majority of which have identity between 40 and 60% to genes in antibiotic resistance gene databases. To study the selection pressure on ARGs, we performed dN/dS analysis specifically on antibiotic inactivation-type ARGs, which exhibited purifying selection compared to contemporary genes.ConclusionAntibiotic resistance has existed throughout microbial evolution and will likely persist, as microbes have the capacity to develop and retain resistance genes through evolutionary processes. The classes of antimicrobial resistance genes profiled and the function of antibiotic-inactivating enzymes from ancient permafrost microbiomes do not seem to be very different from the genes found in the antibiotic era. Additionally, we retrieved 359 putative complete viruses from ancient microbiomes and none of them harboured any ARGs.

Project description:Levels of sex differences for human body size and shape phenotypes are hypothesized to have adaptively reduced following the agricultural transition as part of an evolutionary response to relatively more equal divisions of labor and new technology adoption. In this study, we tested this hypothesis by studying genetic variants associated with five sexually differentiated human phenotypes: height, body mass, hip circumference, body fat percentage, and waist circumference. We first analyzed genome-wide association (GWAS) results for UK Biobank individuals (~194,000 females and ~167,000 males) to identify a total of 114,199 single nucleotide polymorphisms (SNPs) significantly associated with at least one of the studied phenotypes in females, males, or both sexes (P<5x10-8). From these loci we then identified 3,016 SNPs (2.6%) with significant differences in the strength of association between the female- and male-specific GWAS results at a low false-discovery rate (FDR<0.001). Genes with known roles in sexual differentiation are significantly enriched for co-localization with one or more of these SNPs versus SNPs associated with the phenotypes generally but not with sex differences (2.73-fold enrichment; permutation test; P = 0.0041). We also confirmed that the identified variants are disproportionately associated with greater phenotype effect sizes in the sex with the stronger association value. We then used the singleton density score statistic, which quantifies recent (within the last ~3,000 years; post-agriculture adoption in Britain) changes in the frequencies of alleles underlying polygenic traits, to identify a signature of recent positive selection on alleles associated with greater body fat percentage in females (permutation test; P = 0.0038; FDR = 0.0380), directionally opposite to that predicted by the sex differences reduction hypothesis. Otherwise, we found no evidence of positive selection for sex difference-associated alleles for any other trait. Overall, our results challenge the longstanding hypothesis that sex differences adaptively decreased following subsistence transitions from hunting and gathering to agriculture.

Dataset Information

Natural and human-driven selection of a single non-coding body size variant in ancient and modern canids.

Publications

Natural and human-driven selection of a single non-coding body size variant in ancient and modern canids.

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