Genetic variation, which is generated by mutation, recombination and gene flow, can reduce the mean fitness of a population, both now and in the future. This ‘genetic load’ has been estimated in a wide range of animal taxa using various approaches. Advances in genome sequencing and computational techniques now enable us to estimate the genetic load in populations and individuals without direct fitness estimates. Here, we review the classic and contemporary literature of genetic load. We describe approaches to quantify the genetic load in whole-genome sequence data based on evolutionary conservation and annotations. We show that splitting the load into its two components — the realized load (or expressed load) and the masked load (or inbreeding load) — can improve our understanding of the population genetics of deleterious mutations.
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The authors thank D. Charlesworth and A. Caballero for helpful comments on a previous version of the manuscript. C.v.O. was supported by the Royal Society International Collaborations Award (ICA\R1\201194) and the Earth and Life Systems Alliance (ELSA). G.B. and F.R. were supported by the University of Ferrara (Italy). G.B., F.R., A.I. and E.T. were funded by the MIUR PRIN 2017 grant 201794ZXTL to G.B. M.B. was financially supported by the Dutch NWO Veni grant n. 016.Veni.181.050. H.E.M. was funded by an EMBO long-term fellowship (grant 1111-2018) and the European Union’s Horizon 2020 research and innovation programme under a Marie Sklodowska-Curie grant (840519). C.B. is funded by the Wellcome grant WT207492.
The authors declare no competing interests.
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A measure of the capability of an individual or genotype to survive and reproduce.
- Deleterious mutations
Poorly adapted genetic variants that reduce fitness relative to the wild-type variant, thereby contributing to the genetic load. The mutations that remain deleterious across alternative environments are called ‘unconditionally deleterious’.
- Inbreeding depression
The reduction of fitness due to breeding between relatives.
- Effective population size
(Ne). The number of individuals in an idealized population that shows the same amount of genetic drift (that is, random fluctuation of allele frequencies and loss of gene diversity) as the actual population.
(Also known as population bottlenecks). Sharp reductions in the effective population size (Ne) over one or multiple generations.
- Genetic rescue
Artificial (re)introduction of new (or rare) genetic variants into a population with the aims of reducing inbreeding depression, increasing genetic variation and population viability.
- Anchor species
A species that is added to the genome alignment between two evolutionarily distantly related taxa to help connect them and facilitate the identification of conserved elements.
- Mutational spectrum
The rate of different types of DNA mutations in different sequence contexts.
- DNA sequence context
Nucleotide composition around the focal mutation.
- Ultraconserved elements
Highly conserved genomic regions with (near) identical nucleotide sequences in evolutionarily distant taxa.
- Runs of homozygosity
Long and contiguous regions of a diploid genome where all nucleotide sites are homozygous.
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Bertorelle, G., Raffini, F., Bosse, M. et al. Genetic load: genomic estimates and applications in non-model animals. Nat Rev Genet 23, 492–503 (2022). https://doi.org/10.1038/s41576-022-00448-x
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