| Application: | 43626, Quantifying genomic differentiation between the sexes: implications for sex-specific health and infertility |
| Title: | Evaluating human autosomal loci for sexually antagonistic viability selection in two large biobanks |
| Size: | 1299 B |
| Archived: | 17 Sep 2021 |
| Stability: | Complete |
| Personal: | No individual-level data |
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Notes
Sex and sexual differentiation are pervasive across the tree of life. Because females and males often have substantially different functional requirements, we expect selection to differ between the sexes. Recent studies in diverse species, including humans, suggest that sexually antagonistic viability selection creates allele frequency differences between the sexes at many different loci. However, theory and population-level simulations indicate that sex-specific differences in viability would need to be very large to produce and maintain reported levels of between-sex allelic differentiation. We address this contradiction between theoretical predictions and empirical observations by evaluating evidence for sexually antagonistic viability selection on autosomal loci in humans using the largest cohort to date (UK Biobank, n = 487,999) along with a second large, independent cohort (BioVU, n = 93,864). We performed association tests between genetically ascertained sex and autosomal loci. Although we found dozens of genome-wide significant associations, none replicated across cohorts. Moreover, closer inspection revealed that all associations are likely due to cross-hybridization with sex chromosome regions during genotyping. We report loci with potential for mis-hybridization found on commonly used genotyping platforms that should be carefully considered in future genetic studies of sex-specific differences. Despite being well powered to detect allele frequency differences of up to 0.8% between the sexes, we do not detect clear evidence for this signature of sexually antagonistic viability selection on autosomal variation. These findings suggest a lack of strong ongoing sexually antagonistic viability selection acting on single locus autosomal variation in humans.Application 43626
Quantifying genomic differentiation between the sexes: implications for sex-specific health and infertility
Males and females of a given species have the same genomic sequence. Yet, the sexes have distinct physical characters and behaviors. Some of these differences - such as primary sexual characteristics ¬- result from sex-specific genes, namely genes expressed in one sex but not the other. However, most of the phenotypic variation between the sexes - from size to coloration to mating patterns - results from genes expressed in both sexes but in different ways. Since the sexes share the same genomic information, this differentiation in expression, and therefore phenotype, creates a tug-of-war between the sexes over the optimal version of the trait. This genomic tug-of-war between the sexes has the potential to generate differences among the sexes within a generation, potentially leading to important changes within populations over the longer term. However, the extent of this pattern is largely unknown. Importantly, the genomic regions experiencing antagonistic interaction between the sexes are often involved in fertilization and early zygote development, and so understanding the genomic basis of sexual antagonism, may assist in identifying practical solutions for sex-specific health issues, including infertility. The aims of this project are to: i) determine how many genomic regions show a significant difference between the sexes, ii) estimate the strength of selection within these regions, and iii) link sexually differentiated genomic regions with potential associated phenotypes. We hypothesize that genomic regions on the sex chromosomes will have the highest degree of differentiation between the sexes and contribute the most to defective fertility phenotypes. To accomplish these aims, we will adapt classic population genetics statistics to consider males and females as separate populations and measure the divergence between them. The anticipated length of this project is one year.
| Lead investigator: | Dr Patrick Phillips |
| Lead institution: | University of Oregon |
1 Publication
| Pub ID | Title | Author(s) | Year | Journal |
|---|---|---|---|---|
| 3845 | Evaluating human autosomal loci for sexually antagonistic viability selection in two large biobanks | Katja R Kasimatis (+5) | 2020 | Genetics |
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