High-throughput sequencing reveals inbreeding depression in a natural population

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 111; no. 10; pp. 3775 - 3780
• 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: Journal Article
• Language: English
• Published: United States National Academy of Sciences 11.03.2014; National Acad Sciences
• Series: From the Cover
• Subjects: Animals; Biological Sciences; Cellular biology; Correlation analysis; Deoxyribonucleic acid; DNA; Genetic Fitness - genetics; Genetic loci; Genetic Variation; Genetics; Genetics, Population; Heterozygote; High-Throughput Nucleotide Sequencing; Illinois; Inbreeding; Inbreeding coefficient; Inbreeding depression; Infections; Mental depression; Mice; Microsatellites; North Sea; Peromyscus - genetics; Peromyscus polionotus; Phoca - genetics; Phoca - parasitology; Phoca vitulina; Polymorphism; Polymorphism, Single Nucleotide - genetics; Restriction Mapping; Seals; Sequencing; Statistical variance; Illinois; North Sea; heterozygosity fitness correlation; inbreeding; single nucleotide polymorphism; RAD sequencing; genetic variability
• ISSN: 0027-8424; 1091-6490
• DOI: 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.