High-throughput sequencing reveals inbreeding depression in a natural population

Abstract

Proxy measures of genome-wide heterozygosity based on approximately 10 microsatellites have been used to uncover heterozygosity fitness correlations (HFCs) for a wealth of important fitness traits in natural populations. However, effect sizes are typically very small and the underlying mechanisms remain contentious, as a handful of markers usually provides little power to detect inbreeding. We therefore used restriction site associated DNA (RAD) sequencing to accurately estimate genome-wide heterozygosity, an approach transferrable to any organism. As a proof of concept, we first RAD sequenced oldfield mice (Peromyscus polionotus) from a known pedigree, finding strong concordance between the inbreeding coefficient and heterozygosity measured at 13,198 single-nucleotide polymorphisms (SNPs). When applied to a natural population of harbor seals (Phoca vitulina), a weak HFC for parasite infection based on 27 microsatellites strengthened considerably with 14,585 SNPs, the deviance explained by heterozygosity increasing almost fivefold to a remarkable 49%. These findings arguably provide the strongest evidence to date of an HFC being due to inbreeding depression in a natural population lacking a pedigree. They also suggest that under some circumstances heterozygosity may explain far more variation in fitness than previously envisaged.inbreeding | genetic variability | heterozygosity fitness correlation | single nucleotide polymorphism | RAD sequencing

Measuring individual inbreeding in the age of genomics: marker-based measures are better than pedigrees

“…Our results are consistent with two recent studies that used different approaches to evaluate the precision of marker-versus pedigree-based measures of individual inbreeding when using thousands of SNPs. Hoffman et al (2014) found a moderately high correlation between heterozygosity estimated at 413 000 SNPs and F P (r 2 = 0.74) in oldfield mice (Peromyscus polionotus). However, the predicted r 2 between heterozygosity and IBD G (based on estimated identity disequilibrium in their oldfield mice) was ≈1; thus, IBD G was likely more precisely predicted by heterozygosity than by F P in their study population.…”

“…Physical genome maps are currently available for few taxa (Ellegren, 2014). Therefore, our results are encouraging for studies on organisms lacking genome maps and have no choice but to measure individual inbreeding with unmapped loci (for example, Hoffman et al, 2014).…”

“…Keller et al (2011) found that the number of homozygous rare alleles within an individual was more strongly correlated with marker-based estimates of inbreeding than with F P in large simulated populations with short genetic maps (220 cM) and two chromosomes. We expanded on previous work (Keller et al, 2011;Hoffman et al, 2014) by evaluating the performance of marker-and pedigree-based measures of IBD G using simulations where IBD G was known for each individual without error. Additionally, we accounted for variation in the genetic map length, population demography, heterozygosity of the genetic markers and pedigree depth.…”

“…The increasing availability of large-scale molecular genetic data might make it possible to more precisely estimate IBD G with genetic markers than with pedigrees (Keller et al, 2011;Hoffman et al, 2014). For example, IBD G can be estimated as the increase in individual homozygosity relative to Hardy-Weinberg expected homozygosity (F H ) (Purcell et al, 2007).…”

Meiotic recombination shapes precision of pedigree- and marker-based estimates of inbreeding

“…We suggest that it is generally advantageous to use molecular markers in heterozygosity-fitness studies, especially if (1) large numbers (⩾10 000) of SNPs can be genotyped (see, for example, Hoffman et al, 2014;Kardos et al, 2015;Huisman et al, 2016;Wang, 2016), (2) if moderate numbers (∼30-100) of microsatellites can be genotyped and (3) the pedigree covers only few generations or pedigree founders are related.…”