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References
Auton A, Abecasis GR, Altshuler DM, Durbin RM, Bentley DR, Chakravarti A et al. (2015) A global reference for human genetic variation. Nature 526:68–74
Beissinger SR, Westphal MI (1998) On the use of demographic models of population viability in endangered species management. J Wildl Manage 62:821–841
Bittles AH, Neel JV (1994) The costs of human inbreeding and their implications for variations at the DNA level. Nat Genet 8:117–121
Boyko AR, Williamson SH, Indap AR, Degenhardt JD, Hernandez RD, Lohmueller KE et al. (2008). Assessing the evolutionary impact of amino acid mutations in the human genome. PLoS Genet 4:e1000083
Boyle EA, Li YI, Pritchard JK (2017) An expanded view of complex traits: from polygenic to omnigenic. Cell 169:1177–1186
Charlesworth D, Willis JH (2009) The genetics of inbreeding depression. Nat Rev Genet 10:783–796
Chen J, Glémin S, Lascoux M (2017) Genetic diversity and the efficacy of purifying selection across plant and animal species. Mol Biol Evol 34:1417–1428
Davies EK, Peters AD, Keightley PD (1999) High frequency of cryptic deleterious mutations in Caenorhabditis elegans. Science 285:1748–1751
Dukler N, Mughal MR, Ramani R, Huang Y-F, Siepel A (2022) Extreme purifying selection against point mutations in the human genome. Nat Commun 13:1–12
Eyre-Walker A, Keightley PD (2007) The distribution of fitness effects of new mutations. Nat Rev Genet 8:610–618
Eyre-Walker A, Woolfit M, Phelps T (2006) The distribution of fitness effects of new deleterious amino acid mutations in humans. Genetics 173:891–900
Fredrickson RJ, Siminski P, Woolf M, Hedrick PW (2007) Genetic rescue and inbreeding depression in Mexican wolves. Proc R Soc B Biol Sci 274:2365–2371
Gao Z, Waggoner D, Stephens M, Ober C, Przeworski M (2015) An estimate of the average number of recessive lethal mutations carried by humans. Genetics 199:1243–1254
Garcia-Dorado A, Hedrick P (2022). Some hope and many concerns on the future of the vaquita. Heredity (Edinb). https://www.nature.com/articles/s41437-022-00573-7
Gravel S, Henn BM, Gutenkunst RN, Indap AR, Marth GT, Clark AG et al. (2011) Demographic history and rare allele sharing among human populations. Proc Natl Acad Sci 108:11983–11988
Gutenkunst RN, Hernandez RD, Williamson SH, Bustamante CD (2009) Inferring the joint demographic history of multiple populations from multidimensional SNP frequency data. PLoS Genet 5:1–11
Halligan DL, Keightley PD (2009) Spontaneous mutation accumulation studies in evolutionary genetics. Annu Rev Ecol Evol Syst 40:151–172
Hedrick PW, Garcia-Dorado A (2016) Understanding inbreeding depression, purging, and genetic rescue. Trends Ecol Evol 31:940–952
Huang X, Fortier AL, Coffman AJ, Struck TJ, Irby MN, James JE et al. (2021) Inferring genome-wide correlations of mutation fitness effects between populations. Mol Biol Evol 38:4588–4602
Huber CD, Durvasula A, Hancock AM (2018) Gene expression drives the evolution of dominance. Nat Commun 9:1–11
Huber CD, Kim BY, Marsden CD, Lohmueller KE (2017) Determining the factors driving selective effects of new nonsynonymous mutations. Proc Natl Acad Sci 114:4465–4470
Kardos M, Armstrong E, Fitzpatrick S, Hauser S, Hedrick P, Miller J et al. (2021) The crucial role of genome-wide genetic variation in conservation. Proc Natl Acad Sci 118:2021.07.05.451163
Keightley PD (2012) Rates and fitness consequences of new mutations in humans. Genetics 190:295–304
Kim BY, Huber CD, Lohmueller KE (2017) Inference of the distribution of selection coefficients for new nonsynonymous mutations using large samples. Genetics 206:345–361
Koch EM, Schweizer RM, Schweizer TM, Stahler DR, Smith DW, Wayne RK et al. (2019) De novo mutation rate estimation in wolves of known pedigree. Mol Biol Evol 36:2536–2547
Kyriazis CC, Robinson JA, Lohmueller KE (2022). Using computational simulations to quantify genetic load and predict extinction risk. bioRxiv: 1–29. https://doi.org/10.1101/2022.08.12.503792
Kyriazis CC, Wayne RK, Lohmueller KE (2021) Strongly deleterious mutations are a primary determinant of extinction risk due to inbreeding depression. Evol Lett 5:33–47
Li H, Durbin R (2011) Inference of human population history from individual whole-genome sequences. Nature 475:493–496
Lynch M, Blanchard J, Houle D, Kibota T, Schultz S, Vassilieva L et al. (1999) Perspective: Spontaneous deleterious mutation. Evolution (N Y) 53:645–663
Ma X, Kelley JL, Eilertson K, Musharoff S, Degenhardt JD, Martins AL et al. (2013). Population Genomic Analysis Reveals a Rich Speciation and Demographic History of Orang-utans (Pongo pygmaeus and Pongo abelii). PLoS One 8:e77175
MacArthur DG, Tyler-Smith C (2010) Loss-of-function variants in the genomes of healthy humans. Hum Mol Genet 19:125–130
Morin PA, Archer FI, Avila CD, Balacco JR, Bukhman YV, Chow W et al. (2021) Reference genome and demographic history of the most endangered marine mammal, the vaquita. Mol Ecol Resour 21:1008–1020
Murphy D, Elyashiv E, Amster G, Sella G (2021). Broad-scale variation in human genetic diversity levels is predicted by purifying selection on coding and non-coding elements. bioRxiv: 1–18. https://doi.org/10.1101/2021.07.02.450762
Nietlisbach P, Muff S, Reid JM, Whitlock MC, Keller LF (2019) Nonequivalent lethal equivalents: Models and inbreeding metrics for unbiased estimation of inbreeding load. Evol Appl 12:266–279
O’Grady JJ, Brook BW, Reed DH, Ballou JD, Tonkyn DW, Frankham R (2006) Realistic levels of inbreeding depression strongly affect extinction risk in wild populations. Biol Conserv 133:42–51
Pérez-Pereira N, Caballero A, García-Dorado A (2022) Reviewing the consequences of genetic purging on the success of rescue programs. Conserv Genet 23:1–17
Pérez-Pereira N, Pouso R, Rus A, Vilas A, López-Cortegano E, García-Dorado A et al. (2021). Long-term exhaustion of the inbreeding load in Drosophila melanogaster. Heredity (Edinb) 127:373–383
Pickrell JK, Berisa T, Liu JZ, Ségurel L, Tung JY, Hinds DA (2016) Detection and interpretation of shared genetic influences on 42 human traits. Nat Genet 48:709–717
Räikkönen J, Vucetich JA, Peterson RO, Nelson MP (2009) Congenital bone deformities and the inbred wolves (Canis lupus) of Isle Royale. Biol Conserv 142:1025–1031
Robinson JA, Brown C, Kim BY, Lohmueller KE, Wayne RK (2018) Purging of strongly deleterious mutations explains long-term persistence and absence of inbreeding depression in island foxes. Curr Biol 28:3487–3494.e4
Robinson JA, Kyriazis CC, Nigenda-Morales SF, Beichman AC, Rojas-Bracho L, Robertson KM et al. (2022) The critically endangered vaquita is not doomed to extinction by inbreeding depression. Science 639:635–639
Robinson JA, Räikkönen J, Vucetich LM, Vucetich JA, Peterson RO, Lohmueller KE et al. (2019) Genomic signatures of extensive inbreeding in Isle Royale wolves, a population on the threshold of extinction. Sci Adv 5:1–13
Rojas-Bracho L, Taylor BL, Booth C, Thomas L, Jaramillo-Legorreta AM, Nieto-Garcia E et al. (2022) More vaquita porpoises survive than expected. Endanger Species Res 48:225–234
Simmons MJ, Crow JF (1977) Mutations affecting fitness in Drosophila populations. Ann Rev Genet 11:49–78
Tataru P, Mollion M, Glémin S, Bataillon T (2017) Inference of distribution of fitness effects and proportion of adaptive substitutions from polymorphism data. Genetics 207:1103–1119
Tennessen JA, Bigham AW, O’Connor TD, Fu W, Kenny EE, Gravel S et al. (2012) Evolution and functional impact of rare coding variation from deep sequencing of human exomes. Science 337:64–69
Torgerson DG, Boyko AR, Hernandez RD, Indap A, Hu X, White TJ et al. (2009). Evolutionary processes acting on candidate cis-regulatory regions in humans inferred from patterns of polymorphism and divergence. PLoS Genet 5:e1000592
Wade EE, Kyriazis CC, Cavassim MIA, Lohmueller KE (2022). Quantifying the fraction of new mutations that are recessive lethal. bioRxiv: 1–24. https://doi.org/10.1101/2022.04.22.489225
Wiedenfeld DA, Alberts AC, Angulo A, Bennett EL, Byers O, Contreras-MacBeath T et al. (2021) Conservation resource allocation, small population resiliency, and the fallacy of conservation triage. Conserv Biol 35:1388–1395
Acknowledgements
We are grateful to three anonymous reviewers for constructive comments on this manuscript. CCK and KEL were supported by National Institutes of Health (NIH) grant R35GM119856 (to KEL). ACB was supported by the Biological Mechanisms of Healthy Aging Training Program, NIH T32AG066574. SFN-M was supported by the Mexican National Council for Science and Technology (CONACYT) postdoctoral fellowship 724094 and the Mexican Secretariat of Agriculture and Rural Development postdoctoral fellowship. We dedicate this work to our mentor, colleague, and friend Bob Wayne, who passed away in December 2022.
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Kyriazis, C.C., Robinson, J.A., Nigenda-Morales, S.F. et al. Models based on best-available information support a low inbreeding load and potential for recovery in the vaquita. Heredity 130, 183–187 (2023). https://doi.org/10.1038/s41437-023-00608-7
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DOI: https://doi.org/10.1038/s41437-023-00608-7