The crucial role of genome-wide genetic variation in conservation

The unprecedented rate of extinction calls for efficient use of genetics to help conserve biodiversity. Several recent genomic and simulation-based studies have argued that the field of conservation biology has placed too much focus on the conservation of genome-wide genetic variation, and that this approach should be replaced with another that focuses instead on managing the subset of functional genetic variation that is thought to affect fitness. Here, we critically evaluate the feasibility and likely benefits of this approach in conservation. We find that population genetics theory and empirical results show that the conserving genome-wide genetic variation is generally the best approach to prevent inbreeding depression and loss of adaptive potential from driving populations towards extinction. Focusing conservation efforts on presumably functional genetic variation will only be feasible occasionally, often misleading, and counterproductive when prioritized over genome-wide genetic variation. Given the increasing rate of habitat loss and other environmental changes, failure to recognize the detrimental effects of lost genome-wide variation on long-term population viability will only worsen the biodiversity crisis.

[1]  U. Ramakrishnan,et al.  Genomic evidence for inbreeding depression and purging of deleterious genetic variation in Indian tigers , 2021, Proceedings of the National Academy of Sciences.

[2]  J. DeWoody,et al.  Genetic load has potential in large populations but is realized in small inbred populations , 2021, Evolutionary applications.

[3]  A. Prasad,et al.  Evaluating the role of reference-genome phylogenetic distance on evolutionary inference , 2021, bioRxiv.

[4]  A. Albrechtsen,et al.  High genetic diversity and low differentiation reflect the ecological versatility of the African leopard , 2021, Current Biology.

[5]  R. Frankham,et al.  Genetic rescue: A critique of the evidence supports maximizing genetic diversity rather than minimizing the introduction of putatively harmful genetic variation , 2020 .

[6]  Voichita D. Marinescu,et al.  A comparative genomics multitool for scientific discovery and conservation , 2020, Nature.

[7]  E. Anderson,et al.  A complex phenotype in salmon controlled by a simple change in migratory timing , 2020, Science.

[8]  G. Luikart,et al.  Evaluating the outcomes of genetic rescue attempts , 2020, Conservation biology : the journal of the Society for Conservation Biology.

[9]  J. C. Teixeira,et al.  The inflated significance of neutral genetic diversity in conservation genetics , 2020, Proceedings of the National Academy of Sciences.

[10]  A. Phillippy,et al.  Reference genome and demographic history of the most endangered marine mammal, the vaquita , 2020, bioRxiv.

[11]  Andrew J. DeWoody,et al.  Genetic load has potential in large populations but is realized in small populations , 2020 .

[12]  A. Whiteley,et al.  The ecological causes and consequences of hard and soft selection. , 2021, Ecology letters.

[13]  M. Hofreiter,et al.  Hyena paleogenomes reveal a complex evolutionary history of cross-continental gene flow between spotted and cave hyena , 2020, Science Advances.

[14]  L. Keller,et al.  Purging of highly deleterious mutations through severe bottlenecks in Alpine ibex , 2020, Nature Communications.

[15]  Gideon S. Bradburd,et al.  Genomic and Fitness Consequences of Genetic Rescue in Wild Populations , 2019, Current Biology.

[16]  A. Ives,et al.  Inbreeding reduces long-term growth of Alpine ibex populations , 2019, Nature Ecology & Evolution.

[17]  Danny E. Miller,et al.  Long live the king: chromosome-level assembly of the lion (Panthera leo) using linked-read, Hi-C, and long-read data , 2019, BMC Biology.

[18]  Christopher C. Kyriazis,et al.  Strongly deleterious mutations are a primary determinant of extinction risk due to inbreeding depression , 2019, bioRxiv.

[19]  G. Luikart,et al.  The genetic architecture of fitness drives population viability during rapid environmental change , 2019, bioRxiv.

[20]  K. Nielsen,et al.  Genomic variation predicts adaptive evolutionary responses better than population bottleneck history , 2019, PLoS genetics.

[21]  J. Mann,et al.  Is MHC diversity a better marker for conservation than neutral genetic diversity? A case study of two contrasting dolphin populations , 2019, Ecology and evolution.

[22]  J. Ewen,et al.  Little Adaptive Potential in a Threatened Passerine Bird , 2019, Current Biology.

[23]  P. Hedrick,et al.  Genetics and extinction and the example of Isle Royale wolves , 2019, Animal Conservation.

[24]  Alvaro G. Hernandez,et al.  Sex-dependent dominance maintains migration supergene in rainbow trout , 2018, Nature Ecology & Evolution.

[25]  Bernard Y. Kim,et al.  Purging of Strongly Deleterious Mutations Explains Long-Term Persistence and Absence of Inbreeding Depression in Island Foxes , 2018, Current Biology.

[26]  M. Kardos,et al.  The Peril of Gene-Targeted Conservation. , 2018, Trends in ecology & evolution.

[27]  R. Wayne,et al.  Genomic signatures of extensive inbreeding in Isle Royale wolves, a population on the threshold of extinction , 2018, Science Advances.

[28]  L. Keller,et al.  Sex-specific additive genetic variances and correlations for fitness in a song sparrow (Melospiza melodia) population subject to natural immigration and inbreeding , 2018, bioRxiv.

[29]  Brenna R. Forester,et al.  Improving conservation policy with genomics: a guide to integrating adaptive potential into U.S. Endangered Species Act decisions for conservation practitioners and geneticists , 2018, Conservation Genetics.

[30]  F. Jiggins,et al.  Adaptive introgression underlies polymorphic seasonal camouflage in snowshoe hares , 2018, Science.

[31]  Michele R. Dudash,et al.  Call for a Paradigm Shift in the Genetic Management of Fragmented Populations , 2018 .

[32]  R. Lacy,et al.  Maintenance of genetic variation in quantitative traits of a woodland rodent during generations of captive breeding , 2018, Conservation Genetics.

[33]  Monika Böhm,et al.  Patterns and biases of climate change threats in the IUCN Red List , 2018, Conservation biology : the journal of the Society for Conservation Biology.

[34]  M. Noor,et al.  Are Lethal Alleles Too Abundant in Humans? , 2017, Trends in genetics : TIG.

[35]  T. Sicheritz-Pontén,et al.  The wolf reference genome sequence (Canis lupus lupus) and its implications for Canis spp. population genomics , 2017, BMC Genomics.

[36]  Yang I Li,et al.  An Expanded View of Complex Traits: From Polygenic to Omnigenic , 2017, Cell.

[37]  Basten L. Snoek,et al.  Contribution of trans regulatory eQTL to cryptic genetic variation in C. elegans , 2017, bioRxiv.

[38]  F. Allendorf Genetics and the conservation of natural populations: allozymes to genomes , 2017, Molecular ecology.

[39]  D. Pearse,et al.  Saving the spandrels? Adaptive genomic variation in conservation and fisheries management. , 2016, Journal of fish biology.

[40]  P. Hedrick,et al.  Understanding Inbreeding Depression, Purging, and Genetic Rescue. , 2016, Trends in ecology & evolution.

[41]  O. Liberg,et al.  Genetic rescue in a severely inbred wolf population , 2016, Molecular ecology.

[42]  Adam Auton,et al.  A Pedigree-Based Map of Recombination in the Domestic Dog Genome , 2016, G3: Genes, Genomes, Genetics.

[43]  Elizabeth P. Murchison,et al.  Rapid evolutionary response to a transmissible cancer in Tasmanian devils , 2016, Nature Communications.

[44]  S. Piertney,et al.  Evidence of the phenotypic expression of a lethal recessive allele under inbreeding in a wild population of conservation concern. , 2016, The Journal of animal ecology.

[45]  Diego Ortega-Del Vecchyo,et al.  Genomic Flatlining in the Endangered Island Fox , 2016, Current Biology.

[46]  H. Ellegren,et al.  Whole‐genome resequencing of extreme phenotypes in collared flycatchers highlights the difficulty of detecting quantitative trait loci in natural populations , 2016, Molecular ecology resources.

[47]  Harry Hemingway,et al.  Health and population effects of rare gene knockouts in adult humans with related parents , 2015, Science.

[48]  S. Lien,et al.  Sex-dependent dominance at a single locus maintains variation in age at maturity in salmon , 2015, Nature.

[49]  J. Wingfield,et al.  A supergene determines highly divergent male reproductive morphs in the ruff , 2015, Nature Genetics.

[50]  J. Hadfield,et al.  Are molecular markers useful predictors of adaptive potential? , 2015, Ecology letters.

[51]  B. Burns,et al.  Ambiguity in guideline definitions introduces assessor bias and influences consistency in IUCN Red List status assessments , 2015, Front. Ecol. Evol..

[52]  R. Frankham Genetic rescue of small inbred populations: meta-analysis reveals large and consistent benefits of gene flow. , 2015, Molecular ecology.

[53]  Peter H. Sudmant,et al.  Mountain gorilla genomes reveal the impact of long-term population decline and inbreeding , 2015, Science.

[54]  G. Luikart,et al.  Measuring individual inbreeding in the age of genomics: marker-based measures are better than pedigrees , 2015, Heredity.

[55]  N. J. Ouborg,et al.  Genomics and the challenging translation into conservation practice. , 2015, Trends in ecology & evolution.

[56]  Vitor R. C. Aguiar,et al.  Mapping Bias Overestimates Reference Allele Frequencies at the HLA Genes in the 1000 Genomes Project Phase I Data , 2014, G3: Genes, Genomes, Genetics.

[57]  Timothy B Sackton,et al.  Natural Selection Constrains Neutral Diversity across A Wide Range of Species , 2014, bioRxiv.

[58]  D. Balding,et al.  Relatedness in the post-genomic era: is it still useful? , 2014, Nature Reviews Genetics.

[59]  M. Stephens,et al.  An Estimate of the Average Number of Recessive Lethal Mutations Carried by Humans , 2014, Genetics.

[60]  G. Luikart,et al.  Evaluating the role of inbreeding depression in heterozygosity‐fitness correlations: how useful are tests for identity disequilibrium? , 2014, Molecular ecology resources.

[61]  P. Hedrick,et al.  Genetic rescue in Isle Royale wolves: genetic analysis and the collapse of the population , 2014, Conservation Genetics.

[62]  S. Piertney,et al.  Selection maintains MHC diversity through a natural population bottleneck. , 2012, Molecular biology and evolution.

[63]  A. García-Dorado Understanding and Predicting the Fitness Decline of Shrunk Populations: Inbreeding, Purging, Mutation, and Standard Selection , 2012, Genetics.

[64]  H. Hoekstra,et al.  Molecular spandrels: tests of adaptation at the genetic level , 2011, Nature Reviews Genetics.

[65]  P. Cardoso,et al.  Adapting the IUCN Red List criteria for invertebrates , 2011 .

[66]  M. Whitlock,et al.  Inferences About the Distribution of Dominance Drawn From Yeast Gene Knockout Data , 2011, Genetics.

[67]  P. Visscher,et al.  Reconciling the analysis of IBD and IBS in complex trait studies , 2010, Nature Reviews Genetics.

[68]  S. O’Brien,et al.  Genetic Restoration of the Florida Panther , 2010, Science.

[69]  P. Visscher,et al.  Common SNPs explain a large proportion of heritability for human height , 2011 .

[70]  A. Agrawal Ecological Determinants of Mutation Load and Inbreeding Depression in Subdivided Populations , 2010, The American Naturalist.

[71]  M. Lynch Rate, molecular spectrum, and consequences of human mutation , 2010, Proceedings of the National Academy of Sciences.

[72]  D. Charlesworth,et al.  The genetics of inbreeding depression , 2009, Nature Reviews Genetics.

[73]  Judy H. Cho,et al.  Finding the missing heritability of complex diseases , 2009, Nature.

[74]  G. Bell,et al.  Evolutionary rescue can prevent extinction following environmental change. , 2009, Ecology letters.

[75]  David J. Hosken,et al.  Inbreeding, inbreeding depression and extinction , 2008, Conservation Genetics.

[76]  H. Ellegren,et al.  Genetic basis of fitness differences in natural populations , 2008, Nature.

[77]  P. Keightley,et al.  A Comparison of Models to Infer the Distribution of Fitness Effects of New Mutations , 2013, Genetics.

[78]  B. Charlesworth,et al.  Direct estimation of per nucleotide and genomic deleterious mutation rates in Drosophila , 2007, Nature.

[79]  Jeffery P. Demuth,et al.  The Evolution of Mammalian Gene Families , 2006, PloS one.

[80]  A. Hoffmann,et al.  Limits to the adaptive potential of small populations , 2006 .

[81]  D. H. Reed,et al.  Realistic levels of inbreeding depression strongly affect extinction risk in wild populations , 2006 .

[82]  H. Resit Akçakaya,et al.  Use and misuse of the IUCN Red List Criteria in projecting climate change impacts on biodiversity , 2006 .

[83]  G. Luikart,et al.  Genetic rescue of an insular population of large mammals , 2006, Proceedings of the Royal Society B: Biological Sciences.

[84]  R. Frankham Genetics and extinction , 2005 .

[85]  R. Frankham,et al.  Most species are not driven to extinction before genetic factors impact them. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[86]  N. Barton,et al.  EFFECTS OF GENETIC DRIFT ON VARIANCE COMPONENTS UNDER A GENERAL MODEL OF EPISTASIS , 2004, Evolution; international journal of organic evolution.

[87]  K. Ralls,et al.  GENETIC STATUS AND MANAGEMENT OF CALIFORNIA CONDORS , 2004 .

[88]  P. Hedrick,et al.  PERSPECTIVE: DETECTING ADAPTIVE MOLECULAR POLYMORPHISM: LESSONS FROM THE MHC , 2003, Evolution; international journal of organic evolution.

[89]  S. Barrett,et al.  PERSPECTIVE: PURGING THE GENETIC LOAD: A REVIEW OF THE EXPERIMENTAL EVIDENCE , 2002, Evolution; international journal of organic evolution.

[90]  R. May,et al.  Taxonomic Bias in Conservation Research , 2002, Science.

[91]  L. Keller,et al.  Inbreeding effects in wild populations. , 2002 .

[92]  M. Whitlock Selection, load and inbreeding depression in a large metapopulation. , 2002, Genetics.

[93]  R. Frankham,et al.  Inbreeding and extinction: Effects of purging , 2001, Conservation Genetics.

[94]  R. Frankham,et al.  HOW CLOSELY CORRELATED ARE MOLECULAR AND QUANTITATIVE MEASURES OF GENETIC VARIATION? A META‐ANALYSIS , 2001, Evolution; international journal of organic evolution.

[95]  R. Frankham,et al.  Genetic management of chondrodystrophy in California condors , 2000 .

[96]  W. Potts,et al.  Male-male competition magnifies inbreeding depression in wild house mice. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[97]  Edwin H. Lowe,et al.  Do population size bottlenecks reduce evolutionary potential? , 1999 .

[98]  Peter D. Keightley,et al.  High genomic deleterious mutation rates in hominids , 1999, Nature.

[99]  J. L. Bouzat,et al.  Tracking the long-term decline and recovery of an isolated population , 1998, Science.

[100]  R. Lacy,et al.  EFFECTIVENESS OF SELECTION IN REDUCING THE GENETIC LOAD IN POPULATIONS OF PEROMYSCUS POLIONOTUS DURING GENERATIONS OF INBREEDING , 1998, Evolution; international journal of organic evolution.

[101]  I. Hanski,et al.  Inbreeding and extinction in a butterfly metapopulation , 1998, Nature.

[102]  R. Frankham,et al.  How large must populations be to retain evolutionary potential? , 1998 .

[103]  Robert C. Lacy,et al.  Importance of Genetic Variation to the Viability of Mammalian Populations , 1997 .

[104]  J. Ballou,et al.  Ancestral inbreeding only minimally affects inbreeding depression in mammalian populations. , 1997, The Journal of heredity.

[105]  R. Lacy,et al.  HIERARCHICAL ANALYSIS OF INBREEDING DEPRESSION IN PEROMYSCUS POLIONOTUS , 1996, Evolution; international journal of organic evolution.

[106]  M. Lynch,et al.  Estimation of deleterious-mutation parameters in natural populations. , 1996, Genetics.

[107]  R. Lande,et al.  THE ROLE OF GENETIC VARIATION IN ADAPTATION AND POPULATION PERSISTENCE IN A CHANGING ENVIRONMENT , 1996, Evolution; international journal of organic evolution.

[108]  M. Lynch,et al.  Mutation Accumulation and the Extinction of Small Populations , 1995, The American Naturalist.

[109]  M. Lynch,et al.  EVOLUTION AND EXTINCTION IN A CHANGING ENVIRONMENT: A QUANTITATIVE‐GENETIC ANALYSIS , 1995, Evolution; international journal of organic evolution.

[110]  R. Gomulkiewicz,et al.  WHEN DOES EVOLUTION BY NATURAL SELECTION PREVENT EXTINCTION? , 1995, Evolution; international journal of organic evolution.

[111]  A. Harcourt,et al.  Population Viability Estimates: Theory and Practice for a Wild Gorilla Population , 1995 .

[112]  R. Lande RISK OF POPULATION EXTINCTION FROM FIXATION OF NEW DELETERIOUS MUTATIONS , 1994, Evolution; international journal of organic evolution.

[113]  L. Scott Mills,et al.  Demographic Consequences of Inbreeding in Remnant Populations , 1994, The American Naturalist.

[114]  T. Caro,et al.  Ecological and genetic factors in conservation: a cautionary tale. , 1994, Science.

[115]  R. Lande NEUTRAL THEORY OF QUANTITATIVE GENETIC VARIANCE IN AN ISLAND MODEL WITH LOCAL EXTINCTION AND COLONIZATION , 1992, Evolution; international journal of organic evolution.

[116]  P. Hedrick,et al.  MHC Polymorphism and the Design of Captive Breeding Programs: Simple Solutions Are Not the Answer , 1991 .

[117]  R. Vrijenhoek,et al.  Let's Not Throw the Baby Out with the Bathwater: A Comment on Management for MHC Diversity in Captive Populations , 1991 .

[118]  A. Hughes MHC Polymorphism and the Design of Captive Breeding Programs , 1991 .

[119]  S. Haig,et al.  Management Options for Preserving Genetic Diversity: Reintroduction of Guam Rails to the Wild , 1990 .

[120]  Jonathan D. Ballou,et al.  Estimates of Lethal Equivalents and the Cost of Inbreeding in Mammals , 1988 .

[121]  C. Goodnight EPISTASIS AND THE EFFECT OF FOUNDER EVENTS ON THE ADDITIVE GENETIC VARIANCE , 1988, Evolution; international journal of organic evolution.

[122]  R. Lande,et al.  Viable Populations for Conservation: Effective population size, genetic variation, and their use in population management , 1987 .

[123]  C. Goodnight ON THE EFFECT OF FOUNDER EVENTS ON EPISTATIC GENETIC VARIANCE , 1987, Evolution; international journal of organic evolution.

[124]  E. H. Bryant,et al.  The Effect of an Experimental Bottleneck upon Quantitative Genetic Variation in the Housefly. , 1986, Genetics.

[125]  S. Gould,et al.  The spandrels of San Marco and the Panglossian paradigm: a critique of the adaptationist programme , 1979, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[126]  A. Jacquard,et al.  Inbreeding: one word, several meanings. , 1975, Theoretical population biology.

[127]  O. Frankel Genetic conservation: our evolutionary responsibility. , 1974, Genetics.

[128]  N. Morton,et al.  AN ESTIMATE OF THE MUTATIONAL DAMAGE IN MAN FROM DATA ON CONSANGUINEOUS MARRIAGES. , 1956, Proceedings of the National Academy of Sciences of the United States of America.

[129]  J. B. S. Haldane,et al.  The Effect of Variation of Fitness , 1937, The American Naturalist.

[130]  Pall I. Olason,et al.  Genomic consequences of intensive inbreeding in an isolated wolf population , 2017, Nature Ecology & Evolution.

[131]  Philipp W. Messer,et al.  SLiM 2: Flexible, Interactive Forward Genetic Simulations , 2017, Molecular biology and evolution.

[132]  D. Tallmon,et al.  Genetic rescue to the rescue. , 2015, Trends in ecology & evolution.

[133]  J. Piedrafita,et al.  Analysis of founder-specific inbreeding depression on birth weight in Ripollesa lambs. , 2009, Journal of animal science.

[134]  R. Lacy Should we select genetic alleles in our conservation breeding programs , 2000 .

[135]  L. Laikre HEREDITARY DEFECTS AND CONSERVATION GENETIC MANAGEMENT OF CAPTIVE POPULATIONS , 1999 .

[136]  Robert C. Lacy,et al.  VORTEX: a computer simulation model for population viability analysis , 1993 .

[137]  R. G. Rogers,et al.  Life expectancies of cigarette smokers and nonsmokers in the United States. , 1991, Social science & medicine.

[138]  Daniel Simberloff,et al.  The Contribution of Population and Community Biology to Conservation Science , 1988 .

[139]  Deborah Charlesworth,et al.  INBREEDING DEPRESSION AND ITS EVOLUTIONARY CONSEQUENCES , 1987 .

[140]  F. Allendorf,et al.  Protein variation, fitness, and captive propagation , 1986 .

[141]  J. Crow,et al.  Mutations affecting fitness in Drosophila populations. , 1977, Annual review of genetics.