High-throughput sequencing reveals inbreeding depression in a natural population

Proc Natl Acad Sci U S A. 2014 Mar 11;111(10):3775-80. doi: 10.1073/pnas.1318945111. Epub 2014 Feb 28.


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.

Keywords: RAD sequencing; genetic variability; heterozygosity fitness correlation; inbreeding; single nucleotide polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Genetic Fitness / genetics*
  • Genetic Variation*
  • Genetics, Population
  • Heterozygote*
  • High-Throughput Nucleotide Sequencing
  • Illinois
  • Inbreeding*
  • North Sea
  • Peromyscus / genetics*
  • Phoca / genetics*
  • Phoca / parasitology
  • Polymorphism, Single Nucleotide / genetics
  • Restriction Mapping

Associated data

  • SRA/PRJEB5164