High-throughput sequencing reveals inbreeding depression in a natural population

• Published in: Proceedings of the National Academy of Sciences
• Main Authors: Hoffman, Joseph, Simpson, Fraser, Patrice, David, Rijks, Jolianne, Kuiken, Thijs, Thorne, Michael, Lacy, Robert, Dasmahapatra, Kanchon
• Format: Article in Journal/Newspaper
• Language: English
• Published: Proceedings of the National Academy of Sciences 2014
• Subjects: single nucleotide polymorphism; RAD sequencing; heterozygosity fitness correlation; genetic variability; inbreeding; Oldfield; Phoca vitulina
• Online Access: https://pub.uni-bielefeld.de/record/2663373

Hoffman J, Simpson F, Patrice D, et al. High-throughput sequencing reveals inbreeding depression in a natural population. Proceedings of the National Academy of Sciences of the United States of America . 2014;111(10):3775-3780. 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.