Genome-to-phenome research in agriculture aims to improve crops through in silico predictions. Genome-wide association study (GWAS) is potent in identifying genomic loci that underlie important traits. As a statistical method, increasing the sample quantity, data quality, or diversity of the GWAS dataset positively impacts GWAS power. For more precise breeding, concrete candidate genes with exact functional variants must be discovered. Many post-GWAS methods have been developed to narrow down the associated genomic regions and, ideally, to predict candidate genes and causative mutations (CMs). Historical natural selection and breeding-related artificial selection both act to change the frequencies of different alleles of genes that control phenotypes. With higher diversity and more extensive GWAS datasets, there is an increased chance of multiple alleles with independent CMs in a single causal gene. This can be caused by the presence of samples from geographically isolated regions that arose during natural or artificial selection. This simple fact is a complicating factor in GWAS-driven discoveries. Currently, none of the existing association methods address this issue and need to identify multiple alleles and, more specifically, the actual CMs. Therefore, we developed a tool that computes a score for a combination of variant positions in a single candidate gene and, based on the highest score, identifies the best number and combination of CMs. The tool is publicly available as a Python package on GitHub, and we further created a web-based Multiple Alleles discovery (MADis) tool that supports soybean and is hosted in SoyKB (https://soykb.org/SoybeanMADisTool/). We tested and validated the algorithm and presented the utilization of MADis in a pod pigmentation L1 gene case study with multiple CMs from natural or artificial selection. Finally, we identified a candidate gene for the pod color L2 locus and predicted the existence of multiple alleles that potentially cause loss of pod pigmentation. In this work, we show how a genomic analysis can be employed to explore the natural and artificial selection of multiple alleles and, thus, improve and accelerate crop breeding in agriculture.

• Klíčová slova
• GWAS, alleles, breeding, causal gene, causative mutation, genetic variation, soybean,
• Publikační typ
• časopisecké články MeSH

In European and many African, Middle Eastern and southern Asian populations, lactase persistence (LP) is the most strongly selected monogenic trait to have evolved over the past 10,000 years1. Although the selection of LP and the consumption of prehistoric milk must be linked, considerable uncertainty remains concerning their spatiotemporal configuration and specific interactions2,3. Here we provide detailed distributions of milk exploitation across Europe over the past 9,000 years using around 7,000 pottery fat residues from more than 550 archaeological sites. European milk use was widespread from the Neolithic period onwards but varied spatially and temporally in intensity. Notably, LP selection varying with levels of prehistoric milk exploitation is no better at explaining LP allele frequency trajectories than uniform selection since the Neolithic period. In the UK Biobank4,5 cohort of 500,000 contemporary Europeans, LP genotype was only weakly associated with milk consumption and did not show consistent associations with improved fitness or health indicators. This suggests that other reasons for the beneficial effects of LP should be considered for its rapid frequency increase. We propose that lactase non-persistent individuals consumed milk when it became available but, under conditions of famine and/or increased pathogen exposure, this was disadvantageous, driving LP selection in prehistoric Europe. Comparison of model likelihoods indicates that population fluctuations, settlement density and wild animal exploitation-proxies for these drivers-provide better explanations of LP selection than the extent of milk exploitation. These findings offer new perspectives on prehistoric milk exploitation and LP evolution.

• MeSH
• archeologie * MeSH
• banky biologického materiálu MeSH
• dějiny starověku MeSH
• divoká zvířata MeSH
• frekvence genu MeSH
• genotyp MeSH
• hladomor statistika a číselné údaje   MeSH
• keramika dějiny   MeSH
• kohortové studie MeSH
• laktasa * genetika   MeSH
• lidé MeSH
• mlékárenství * dějiny   MeSH
• mléko * metabolismus   MeSH
• nemoc * MeSH
• populační genetika * MeSH
• selekce (genetika) * MeSH
• zvířata MeSH
• Check Tag
• dějiny starověku MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• historické články MeSH
• Geografické názvy
• Evropa epidemiologie   etnologie   MeSH
• Spojené království MeSH
• Názvy látek
• laktasa * MeSH

Relative contributions of pre-existing vs de novo genomic variation to adaptation are poorly understood, especially in polyploid organisms. We assess this in high resolution using autotetraploid Arabidopsis arenosa, which repeatedly adapted to toxic serpentine soils that exhibit skewed elemental profiles. Leveraging a fivefold replicated serpentine invasion, we assess selection on SNPs and structural variants (TEs) in 78 resequenced individuals and discover significant parallelism in candidate genes involved in ion homeostasis. We further model parallel selection and infer repeated sweeps on a shared pool of variants in nearly all these loci, supporting theoretical expectations. A single striking exception is represented by TWO PORE CHANNEL 1, which exhibits convergent evolution from independent de novo mutations at an identical, otherwise conserved site at the calcium channel selectivity gate. Taken together, this suggests that polyploid populations can rapidly adapt to environmental extremes, calling on both pre-existing variation and novel polymorphisms.

• MeSH
• alely * MeSH
• Arabidopsis účinky léků   genetika   MeSH
• fyziologická adaptace účinky léků   genetika   MeSH
• genom rostlinný * MeSH
• jednonukleotidový polymorfismus MeSH
• mutace MeSH
• polyploidie * MeSH
• proteiny huseníčku genetika   metabolismus   MeSH
• půda chemie   MeSH
• sekologanin-tryptaminové alkaloidy metabolismus   MeSH
• vápníkové kanály metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• proteiny huseníčku MeSH
• půda MeSH
• sekologanin-tryptaminové alkaloidy MeSH
• serpentine (alkaloid) MeSH Prohlížeč
• TPC1 protein, Arabidopsis MeSH Prohlížeč
• vápníkové kanály MeSH

BACKGROUND: Human population history in the Holocene was profoundly impacted by changes in lifestyle following the invention and adoption of food-production practices. These changes triggered significant increases in population sizes and expansions over large distances. Here we investigate the population history of the Fulani, a pastoral population extending throughout the African Sahel/Savannah belt. RESULTS: Based on genome-wide analyses we propose that ancestors of the Fulani population experienced admixture between a West African group and a group carrying both European and North African ancestries. This admixture was likely coupled with newly adopted herding practices, as it resulted in signatures of genetic adaptation in contemporary Fulani genomes, including the control element of the LCT gene enabling carriers to digest lactose throughout their lives. The lactase persistence (LP) trait in the Fulani is conferred by the presence of the allele T-13910, which is also present at high frequencies in Europe. We establish that the T-13910 LP allele in Fulani individuals analysed in this study lies on a European haplotype background thus excluding parallel convergent evolution. We furthermore directly link the T-13910 haplotype with the Lactase Persistence phenotype through a Genome Wide Association study (GWAS) and identify another genomic region in the vicinity of the SPRY2 gene associated with glycaemic measurements after lactose intake. CONCLUSIONS: Our findings suggest that Eurasian admixture and the European LP allele was introduced into the Fulani through contact with a North African population/s. We furthermore confirm the link between the lactose digestion phenotype in the Fulani to the MCM6/LCT locus by reporting the first GWAS of the lactase persistence trait. We also explored other signals of recent adaptation in the Fulani and identified additional candidates for selection to adapt to herding life-styles.

• Klíčová slova
• Adaptive gene-flow, Fulani people, GWAS, Lactase persistence, Pastoralism,
• MeSH
• celogenomová asociační studie MeSH
• černoši genetika   MeSH
• laktasa genetika   MeSH
• lidé MeSH
• molekulární evoluce MeSH
• osoby s přechodným pobytem a migranti MeSH
• tok genů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• laktasa MeSH

BACKGROUND: Dietary changes associated to shifts in subsistence strategies during human evolution may have induced new selective pressures on phenotypes, as currently held for lactase persistence. Similar hypotheses exist for arylamine N-acetyltransferase 2 (NAT2) mediated acetylation capacity, a well-known pharmacogenetic trait with wide inter-individual variation explained by polymorphisms in the NAT2 gene. The environmental causative factor (if any) driving its evolution is as yet unknown, but significant differences in prevalence of acetylation phenotypes are found between hunter-gatherer and food-producing populations, both in sub-Saharan Africa and worldwide, and between agriculturalists and pastoralists in Central Asia. These two subsistence strategies also prevail among sympatric populations of the African Sahel, but knowledge on NAT2 variation among African pastoral nomads was up to now very scarce. Here we addressed the hypothesis of different selective pressures associated to the agriculturalist or pastoralist lifestyles having acted on the evolution of NAT2 by sequencing the gene in 287 individuals from five pastoralist and one agriculturalist Sahelian populations. RESULTS: We show that the significant NAT2 genetic structure of African populations is mainly due to frequency differences of three major haplotypes, two of which are categorized as decreased function alleles (NAT2*5B and NAT2*6A), particularly common in populations living in arid environments, and one fast allele (NAT2*12A), more frequently detected in populations living in tropical humid environments. This genetic structure does associate more strongly with a classification of populations according to ecoregions than to subsistence strategies, mainly because most Sahelian and East African populations display little to no genetic differentiation between them, although both regions hold nomadic or semi-nomadic pastoralist and sedentary agriculturalist communities. Furthermore, we found significantly higher predicted proportions of slow acetylators in pastoralists than in agriculturalists, but also among food-producing populations living in the Sahelian and dry savanna zones than in those living in humid environments, irrespective of their mode of subsistence. CONCLUSION: Our results suggest a possible independent influence of both the dietary habits associated with subsistence modes and the chemical environment associated with climatic zones and biomes on the evolution of NAT2 diversity in sub-Saharan African populations.

• MeSH
• acetylace MeSH
• arylamin-N-acetyltransferasa genetika   MeSH
• černoši MeSH
• haplotypy MeSH
• lékařská genetika MeSH
• lidé MeSH
• molekulární biologie * MeSH
• polymorfismus genetický MeSH
• populační genetika * MeSH
• potraviny MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• subsaharská Afrika MeSH
• Názvy látek
• arylamin-N-acetyltransferasa MeSH
• NAT2 protein, human MeSH Prohlížeč