High-throughput sequencing reveals inbreeding depression in a natural population

• Published in: Proceedings of the National Academy of Sciences
• Main Authors: Hoffman, Joseph I., Simpson, Fraser, David, Patrice, Rijks, Jolianne M., Kuiken, Thijs, Thorne, Michael A.S., Lacy, Robert C., Dasmahapatra, Kanchon K.
• Format: Article in Journal/Newspaper
• Language: unknown
• Published: 2014
• Subjects: Oldfield; Phoca vitulina
• Online Access: http://nora.nerc.ac.uk/id/eprint/505236/; https://doi.org/10.1073/pnas.1318945111

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