Detecting inbreeding depression in structured populations.

Measuring inbreeding and its consequences on fitness is central for many areas in biology including human genetics and the conservation of endangered species. However, there is no consensus on the best method, neither for quantification of inbreeding itself nor for the model to estimate its effect on specific traits. We simulated traits based on simulated genomes from a large pedigree and empirical whole-genome sequences of human data from populations with various sizes and structures (from the 1,000 Genomes project). We compare the ability of various inbreeding coefficients ([Formula: see text]) to quantify the strength of inbreeding depression: allele-sharing, two versions of the correlation of uniting gametes which differ in the weight they attribute to each locus and two identical-by-descent segments-based estimators. We also compare two models: the standard linear model and a linear mixed model (LMM) including a genetic relatedness matrix (GRM) as random effect to account for the nonindependence of observations. We find LMMs give better results in scenarios with population or family structure. Within the LMM, we compare three different GRMs and show that in homogeneous populations, there is little difference among the different [Formula: see text] and GRM for inbreeding depression quantification. However, as soon as a strong population or family structure is present, the strength of inbreeding depression can be most efficiently estimated only if i) the phenotypes are regressed on [Formula: see text] based on a weighted version of the correlation of uniting gametes, giving more weight to common alleles and ii) with the GRM obtained from an allele-sharing relatedness estimator.

Effect of reduced genomic representation on using runs of homozygosity for inbreeding characterization.

Genomic measures of inbreeding based on identical-by-descent (IBD) segments are increasingly used to measure inbreeding and mostly estimated on SNP arrays and whole-genome sequencing (WGS) data. However, some softwares recurrently used for their estimation assume that genomic positions which have not been genotyped are nonvariant. This might be true for WGS data, but not for reduced genomic representations and can lead to spurious IBD segments estimation. In this project, we simulated the outputs of WGS, two SNP arrays of different sizes and RAD-sequencing for three populations with different sizes and histories. We compare the results of IBD segments estimation with two softwares: runs of homozygosity (ROHs) estimated with PLINK and homozygous-by-descent (HBD) segments estimated with RZooRoH. We demonstrate that to obtain meaningful estimates of inbreeding, RZooRoH requires a SNPs density 11 times smaller compared to PLINK: ranks of inbreeding coefficients were conserved among individuals above 22 SNPs/Mb for PLINK and 2 SNPs/Mb for RZooRoH. We also show that in populations with simple demographic histories, distribution of ROHs and HBD segments are correctly estimated with both SNP arrays and WGS. PLINK correctly estimated distribution of ROHs with SNP densities above 22 SNPs/Mb, while RZooRoH correctly estimated distribution of HBD segments with SNPs densities above 11 SNPs/Mb. However, in a population with a more complex demographic history, RZooRoH resulted in better distribution of IBD segments estimation compared to PLINK even with WGS data. Consequently, we advise researchers to use either methods relying on excess homozygosity averaged across SNPs or model-based HBD segments calling methods for inbreeding estimations.

Genomic consequences of colonisation, migration and genetic drift in barn owl insular populations of the eastern Mediterranean.

The study of insular populations was key in the development of evolutionary theory. The successful colonisation of an island depends on the geographic context, and specific characteristics of the organism and the island, but also on stochastic processes. As a result, apparently identical islands may harbour populations with contrasting histories. Here, we use whole genome sequences of 65 barn owls to investigate the patterns of inbreeding and genetic diversity of insular populations in the eastern Mediterranean Sea. We focus on Crete and Cyprus, islands with similar size, climate and distance to mainland, that provide natural replicates for a comparative analysis of the impacts of microevolutionary processes on isolated populations. We show that barn owl populations from each island have a separate origin, Crete being genetically more similar to other Greek islands and mainland Greece, and Cyprus more similar to the Levant. Further, our data show that their respective demographic histories following colonisation were also distinct. On the one hand, Crete harbours a small population and maintains very low levels of gene flow with neighbouring populations. This has resulted in low genetic diversity, strong genetic drift, increased relatedness in the population and remote inbreeding. Cyprus, on the other hand, appears to maintain enough gene flow with the mainland to avoid such an outcome. Our study provides a comparative population genomic analysis of the effects of neutral processes on a classical island-mainland model system. It provides empirical evidence for the role of stochastic processes in determining the fate of diverging isolated populations.