Dietary adaptation of<i>FADS</i>genes in Europe varied across time and geography

Ye, Kaixiong; Gao, Feng; Wang, David; Bar‐Yosef, Ofer; Keinan, Alon

doi:10.1101/111229

Cited by 16 publications

(23 citation statements)

References 104 publications

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“…The first gene, FADS1, is a fatty acid desaturase important for the biosynthesis of omega-3 and omega-6 fatty acids (long-chain polyunsaturated fatty acids, LCPUFA) from plant sources. Recent evidence suggests that the FADS gene family has been an important target of selection in humans during the transition from huntergather to agricultural societies (Ye, Gao, Wang, Bar-Yosef, & Keinan, 2017). Alleles linked to upregulated biosynthesis of LCPUFAs (naturally low in plant-based diets) increased in frequency after the Neolithic Revolution (Ye et al, 2017).…”

Section: Environmental Associations Strengthen Evidence Of Local Admentioning

confidence: 99%

“…Recent evidence suggests that the FADS gene family has been an important target of selection in humans during the transition from huntergather to agricultural societies (Ye, Gao, Wang, Bar-Yosef, & Keinan, 2017). Alleles linked to upregulated biosynthesis of LCPUFAs (naturally low in plant-based diets) increased in frequency after the Neolithic Revolution (Ye et al, 2017). We aligned our homologous FADS1 contig with human transcripts to identify whether P. leucopus had any relevant alleles, but our sequenced populations did not contain SNPs at any relevant loci.…”

Section: Environmental Associations Strengthen Evidence Of Local Admentioning

confidence: 99%

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Signatures of positive selection and local adaptation to urbanization in white‐footed mice (Peromyscus leucopus)

Harris

Munshi‐South

2017

Molecular Ecology

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Urbanization significantly alters natural ecosystems and has accelerated globally. Urban wildlife populations are often highly fragmented by human infrastructure, and isolated populations may adapt in response to local urban pressures. However, relatively few studies have identified genomic signatures of adaptation in urban animals. We used a landscape genomics approach to examine signatures of selection in urban populations of white-footed mice (Peromyscus leucopus) in New York City. We analyzed 154,770 SNPs identified from transcriptome data from 48 P. leucopus individuals from three urban and three rural populations, and used outlier tests to identify evidence of urban adaptation. We accounted for demography by simulating a neutral SNP dataset under an inferred demographic history as a null model for outlier analysis. We also tested whether candidate genes were associated with environmental variables related to urbanization. In total, we detected 381 outlier loci and after stringent filtering, identified and annotated 19 candidate loci. Many of the candidate genes were involved in metabolic processes, and have well-established roles in metabolizing lipids and carbohydrates. Our results indicate that white-footed mice in NYC are adapting at the biomolecular level to local selective pressures in urban habitats. Annotation of outlier loci suggest selection is acting on metabolic pathways in urban populations, likely related to novel diets in cities that differ from diets in less disturbed areas.

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Section: Environmental Associations Strengthen Evidence Of Local Admentioning

confidence: 99%

Section: Environmental Associations Strengthen Evidence Of Local Admentioning

confidence: 99%

Signatures of positive selection and local adaptation to urbanization in white‐footed mice (Peromyscus leucopus)

Harris

Munshi‐South

2017

Molecular Ecology

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“…In particular, another haplotype that is common in, but largely restricted to, the 84 haplotype). This analysis also allows us to prioritize likely causal SNPs, which are currently unknown 85 (Buckley, et al 2017;Ye, et al 2017). If the derived SNP that was selected in modern humans was also 86 selected in Neanderthals, then it must lie in haplotype B, which is defined by just four SNPs (rs174546, 87 rs174547, rs174554 and rs174562).…”

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confidence: 99%

FADS1and the timing of human adaptation to agriculture

Mathieson

2018

Preprint

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1Variation at the FADS1/FADS2 gene cluster is functionally associated with differences in lipid 2 metabolism and is often hypothesized to reflect adaptation to an agricultural diet. Here, we test the 3 evidence for this relationship using both modern and ancient DNA data. We show that almost all the 4 inhabitants of Europe carried the ancestral allele until the derived allele was introduced approximately 5 8,500 years ago by Early Neolithic farming populations. However, we also show that it was not under 6 strong selection in these populations. We find that this allele, and other proposed agricultural adaptations 7 at LCT/MCM6 and SLC22A4, were not strongly selected until much later, perhaps as late as the Bronze 8 Age. Similarly, increased copy number variation at the salivary amylase gene AMY1 is not linked to the 9 development of agriculture although, in this case, the putative adaptation precedes the agricultural 10 transition. Our analysis shows that selection at the FADS locus was not tightly linked to the initial 11 introduction of agriculture and the Neolithic transition. Further, it suggests that the strongest signals of 12 recent human adaptation in Europe did not coincide with the Neolithic transition but with more recent 13 changes in environment, diet or efficiency of selection due to increases in effective population size. 56Greenlandic Inuit population reduces the activity of FADS1, is associated with PUFA levels, and is likely 57 an adaptation to a diet that is extremely high in LC-PUFA from marine sources (Fumagalli, et al. 2015). 58Conversely, a variant that increases expression of FADS2 has been selected in South Asian populations -59 and may be a specific adaptation to a vegetarian diet (Kothapalli, et al. 2016). Reflecting its important 60 role in lipid metabolism, variation at the FADS locus also contributes significantly to variation in lipid 61 levels in present-day populations. As well as directly contributing to variation in PUFA levels, SNPs in 62 haplotype D are among the strongest genome-wide association study (GWAS) signals for triglyceride and 63 cholesterol levels (Teslovich, et al. 2010). Thus, the complex evolutionary history of the region is not 64 only informative about ancient human diets, but also potentially relevant for understanding the 65 distribution of lipid-related disease risk both within and between populations. We therefore aimed to 66 3 characterize the history of the region, by combining inference from ancient and modern DNA data, in 67 order to understand the evolutionary basis of this important functional variation and its relationship with 68 changes in diet. We also compared the evolutionary history of the FADS locus with the histories of other 69 loci involved in dietary adaptation, to see whether we could detect shared patterns of adaptation. 70

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“…This locus (which we refer to 31 as the FADS locus) has been targeted by selection multiple times in human evolution (Ameur, et 32 al. 2012;Mathias, et al 2012;Mathieson, et al 2015;Buckley, et al 2017;Ye, et al 2017;33 Mathieson and Mathieson 2018). There are two LD blocks at the locus, but most studies have 34 focused on the two major haplotypes at LD block 1 (Ameur, et al 2012), which we refer to as 35 the ancestral (A) and derived (D) haplotypes.…”

Section: Introduction 25mentioning

confidence: 99%

“…Haplotype D appears to have been under selection-likely preceding the 38 out-of-Africa bottleneck-in Africa, and is virtually fixed in present-day African populations 39 (Ameur, et al 2012;Mathias, et al 2012). Given this, it is surprising that early Eurasian 40 populations appear to have largely carried the ancestral haplotype, suggesting selection for the 41 ancestral haplotype at some time after the split of present-day African and non-African lineages 42 (Ye, et al 2017;Mathieson and Mathieson 2018). By the Mesolithic-around 10,000 years 43 before present (BP)-the ancestral haplotype was fixed in Europe (Mathieson, et al 2015).…”

Section: Introduction 25mentioning

confidence: 99%

Limited evidence for selection at theFADSlocus in Native American populations

Mathieson

2019

Preprint

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9The FADS locus contains the genes FADS1 and FADS2 that encode enzymes involved in the 10 synthesis of long-chain polyunsaturated fatty acids (LC-PUFA). This locus appears to have been 11 a repeated target of selection in human evolution, likely because dietary input of LC-PUFA 12 varied over time depending on environment and subsistence strategy. Several recent studies 13 have identified selection at the FADS locus in Native American populations, interpreted as 14 evidence for adaptation during or subsequent to the passage through Beringia. Here, we show 15 that these signals of selection are confounded by the presence of parallel adaptation-16 postdating their split from Native Americans-in the European and East Asian populations used 17 in the population branch statistic (PBS) test. This is supported by direct evidence from ancient 18 DNA that one of the putatively selected haplotypes was already common in Northern Eurasia at 19

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Dietary adaptation ofFADSgenes in Europe varied across time and geography

Abstract: Fatty acid desaturase (FADS) genes encode rate-limiting enzymes for the biosynthesis 7 of omega-6 and omega-3 long chain polyunsaturated fatty acids (LCPUFAs). This biosynthesis

Cited by 16 publications

References 104 publications

Signatures of positive selection and local adaptation to urbanization in white‐footed mice (Peromyscus leucopus)

Signatures of positive selection and local adaptation to urbanization in white‐footed mice (Peromyscus leucopus)

FADS1and the timing of human adaptation to agriculture

Limited evidence for selection at theFADSlocus in Native American populations

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