TY - JOUR
T1 - Copy number variation in TAS2R bitter taste receptor genes
T2 - Structure, origin, and population genetics
AU - Roudnitzky, Natacha
AU - Risso, Davide
AU - Drayna, Dennis
AU - Behrens, Maik
AU - Meyerhof, Wolfgang
AU - Wooding, Stephen P.
N1 - Publisher Copyright:
© The Author 2016. Published by Oxford University Press. All rights reserved.
PY - 2016/10/1
Y1 - 2016/10/1
N2 - Bitter taste receptor genes (TAS2Rs) harbor extensive diversity, which is broadly distributed across human populations and strongly associated with taste response phenotypes. The majority of TAS2R variation is composed of single-nucleotide polymorphisms. However, 2 closely positioned loci at 12p13, TAS2R43 and -45, harbor high-frequency deletion (Δ) alleles in which genomic segments are absent, resulting in copy number variation (CNV). To resolve their chromosomal structure and organization, we generated maps using long-range contig alignments and local sequencing across the TAS2R43-45 region. These revealed that the deletion alleles (43Δ and 45Δ) are 37.8 and 32.2kb in length, respectively and span the complete coding region of each gene (~1kb) along with extensive up- and downstream flanking sequence, producing separate CNVs at the 2 loci. Comparisons with a chimpanzee genome, which contained intact homologs of TAS2R43, -45, and nearby TAS2Rs, indicated that the deletions evolved recently, through unequal recombination in a cluster of closely related loci. Population genetic analyses in 946 subjects from 52 worldwide populations revealed that copy number ranged from 0 to 2 at both TAS2R43 and TAS2R45, with 43Δ and 45Δ occurring at high global frequencies (0.33 and 0.18). Estimated recombination rates between the loci were low (ρ = 2.7×10-4; r = 6.6×10-9) and linkage disequilibrium was high (D' = 1.0), consistent with their adjacent genomic positioning and recent origin. Geographic variation pointed to an African origin for the deletions. However, no signatures of natural selection were found in population structure or integrated haplotype scores spanning the region, suggesting that patterns of diversity at TAS2R43 and -45 are primarily due to genetic drift.
AB - Bitter taste receptor genes (TAS2Rs) harbor extensive diversity, which is broadly distributed across human populations and strongly associated with taste response phenotypes. The majority of TAS2R variation is composed of single-nucleotide polymorphisms. However, 2 closely positioned loci at 12p13, TAS2R43 and -45, harbor high-frequency deletion (Δ) alleles in which genomic segments are absent, resulting in copy number variation (CNV). To resolve their chromosomal structure and organization, we generated maps using long-range contig alignments and local sequencing across the TAS2R43-45 region. These revealed that the deletion alleles (43Δ and 45Δ) are 37.8 and 32.2kb in length, respectively and span the complete coding region of each gene (~1kb) along with extensive up- and downstream flanking sequence, producing separate CNVs at the 2 loci. Comparisons with a chimpanzee genome, which contained intact homologs of TAS2R43, -45, and nearby TAS2Rs, indicated that the deletions evolved recently, through unequal recombination in a cluster of closely related loci. Population genetic analyses in 946 subjects from 52 worldwide populations revealed that copy number ranged from 0 to 2 at both TAS2R43 and TAS2R45, with 43Δ and 45Δ occurring at high global frequencies (0.33 and 0.18). Estimated recombination rates between the loci were low (ρ = 2.7×10-4; r = 6.6×10-9) and linkage disequilibrium was high (D' = 1.0), consistent with their adjacent genomic positioning and recent origin. Geographic variation pointed to an African origin for the deletions. However, no signatures of natural selection were found in population structure or integrated haplotype scores spanning the region, suggesting that patterns of diversity at TAS2R43 and -45 are primarily due to genetic drift.
KW - Bitter
KW - Evolution
KW - Genetic
KW - Genomic
KW - Natural selection
KW - Taste receptor
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U2 - 10.1093/chemse/bjw067
DO - 10.1093/chemse/bjw067
M3 - Article
C2 - 27340135
AN - SCOPUS:84991039884
SN - 0379-864X
VL - 41
SP - 649
EP - 659
JO - Chemical Senses
JF - Chemical Senses
IS - 8
ER -