Post by Admin on Aug 26, 2023 22:02:45 GMT
New insights into the phenotypic traits and local ancestry assignments of the Iceman
The high-coverage genome allows us to investigate SNPs of phenotypic significance with sufficient coverage on individual allelic sites. We analyzed 147 SNPs of phenotypic interest, summarized in Table S9, including phenotypic sites examined in the previously published genome.3 We newly reported alleles for phenotypic traits of the Iceman related to reduced hair curliness, black hair color, obesity-related metabolic disorders, reduced freckling, and male-pattern baldness (Tables S9 and S10), in addition to the previously reported phenotype of possibly light skin pigmentation, brown eyes, and blood type O from Keller et al.3 (Table S9).
In particular, five SNPs (rs4988235, rs1050152, rs1495741, rs4751995, rs174546) assumed to be related to the adaptation to an agricultural lifestyle26 suggest that the Iceman was a comparatively slow metabolizer with low concentrations of animal-oriented fatty acids but high concentrations of plant-oriented fatty acids and may have had an intermediate high-density lipoprotein-cholesterol concentration level in general (Tables S9 and S10).
While genetic information cannot yet be used to completely reconstruct the appearance of an individual, genetic models exist for specific phenotypic features. Among those, skin pigmentation is a relatively well-understood trait that can be inferred from genetic data. We examined 170 skin pigmentation-associated SNPs from the UK Biobank genome-wide association study (GWAS) for skin color27,28 and retrieved diploid genotype information from 154 biallelic sites in Iceman. Each phenotype-informative SNP has a different effect size, i.e., the variance in pigmentation explained by individual SNPs is different. Thus, we combined the effect size of each pigmentation-informative SNP together with all examined effective alleles as an indication for the final phenotypic trait. To take effect size impact into consideration, we calculated a weighted genetic score given the individual SNP weight from the UK Biobank GWAS-estimated effect sizes,27,28 which is the weighted proportion of dark pigmentation alleles used as an indicator of skin pigmentation. The weighted genetic score of dark pigmentation in the Iceman is estimated to be 0.591, higher than the score of present-day southern European populations taking Sardinians as an example (Table S11), which the Iceman shares closest genetic affinity to (Figure S1) and which represent the highest level of pigmentation among modern-day European groups,29 although it is lower than the score of ancient LBK farmers and the Luxembourg_Loschbour.DG hunter-gatherer (Table S11).
The high-coverage genome also enables us to explore the ancestral origin of genomic regions along the genome given a set of phased genomes as ancestral references, making it possible to assign SNPs of phenotypic interests to a specific ancestral origin. We assigned local ancestry tracts across 22 autosomes of the Iceman using RFMix30 (Figure 3C), employing an imputed and phased dataset as the reference for WHG and the early Neolithic-farmer-related ancestry (STAR Methods). The WHG ancestry tracts have an average length of 1.174cM on average across 22 autosomes, close to the expected tract length calculated from admixture time and the WHG admixture proportion (1.754cM). In total, genomic tracts of the early Neolithic-farmer-related ancestry account for 91.4% of the genome, with the remaining genomic chunks being assigned to WHG origin (in 8.6%), in line with the global ancestry estimation from qpAdm (90%/10%; Table S4). Based on the assigned local ancestral tract distribution, we inferred two farmer’s diet-related SNPs (rs1495741, rs174546) mentioned above to be of LBK farmer origin, as expected.
The high-coverage genome allows us to investigate SNPs of phenotypic significance with sufficient coverage on individual allelic sites. We analyzed 147 SNPs of phenotypic interest, summarized in Table S9, including phenotypic sites examined in the previously published genome.3 We newly reported alleles for phenotypic traits of the Iceman related to reduced hair curliness, black hair color, obesity-related metabolic disorders, reduced freckling, and male-pattern baldness (Tables S9 and S10), in addition to the previously reported phenotype of possibly light skin pigmentation, brown eyes, and blood type O from Keller et al.3 (Table S9).
In particular, five SNPs (rs4988235, rs1050152, rs1495741, rs4751995, rs174546) assumed to be related to the adaptation to an agricultural lifestyle26 suggest that the Iceman was a comparatively slow metabolizer with low concentrations of animal-oriented fatty acids but high concentrations of plant-oriented fatty acids and may have had an intermediate high-density lipoprotein-cholesterol concentration level in general (Tables S9 and S10).
While genetic information cannot yet be used to completely reconstruct the appearance of an individual, genetic models exist for specific phenotypic features. Among those, skin pigmentation is a relatively well-understood trait that can be inferred from genetic data. We examined 170 skin pigmentation-associated SNPs from the UK Biobank genome-wide association study (GWAS) for skin color27,28 and retrieved diploid genotype information from 154 biallelic sites in Iceman. Each phenotype-informative SNP has a different effect size, i.e., the variance in pigmentation explained by individual SNPs is different. Thus, we combined the effect size of each pigmentation-informative SNP together with all examined effective alleles as an indication for the final phenotypic trait. To take effect size impact into consideration, we calculated a weighted genetic score given the individual SNP weight from the UK Biobank GWAS-estimated effect sizes,27,28 which is the weighted proportion of dark pigmentation alleles used as an indicator of skin pigmentation. The weighted genetic score of dark pigmentation in the Iceman is estimated to be 0.591, higher than the score of present-day southern European populations taking Sardinians as an example (Table S11), which the Iceman shares closest genetic affinity to (Figure S1) and which represent the highest level of pigmentation among modern-day European groups,29 although it is lower than the score of ancient LBK farmers and the Luxembourg_Loschbour.DG hunter-gatherer (Table S11).
The high-coverage genome also enables us to explore the ancestral origin of genomic regions along the genome given a set of phased genomes as ancestral references, making it possible to assign SNPs of phenotypic interests to a specific ancestral origin. We assigned local ancestry tracts across 22 autosomes of the Iceman using RFMix30 (Figure 3C), employing an imputed and phased dataset as the reference for WHG and the early Neolithic-farmer-related ancestry (STAR Methods). The WHG ancestry tracts have an average length of 1.174cM on average across 22 autosomes, close to the expected tract length calculated from admixture time and the WHG admixture proportion (1.754cM). In total, genomic tracts of the early Neolithic-farmer-related ancestry account for 91.4% of the genome, with the remaining genomic chunks being assigned to WHG origin (in 8.6%), in line with the global ancestry estimation from qpAdm (90%/10%; Table S4). Based on the assigned local ancestral tract distribution, we inferred two farmer’s diet-related SNPs (rs1495741, rs174546) mentioned above to be of LBK farmer origin, as expected.