Advertisement

Conservation Genetics

, Volume 19, Issue 6, pp 1295–1307 | Cite as

Runs of homozygosity have utility in mammalian conservation and evolutionary studies

  • Anna Brüniche-OlsenEmail author
  • Kenneth F. Kellner
  • Chase J. Anderson
  • J. Andrew DeWoody
Research Article

Abstract

Runs of homozygosity (ROHs) arise due the transmission from parents to offspring of segments that are either identical by decent (IBD) or identical by state (IBS). The former is due to consanguineous matings whereas the latter is due to demographic processes. ROHs reduce individual nucleotide diversity (θ) as a function of homozygosity, and thus ROH distributions and θ are expected to vary among species because inbreeding levels, recombination rates, and demographic histories vary widely. To help interpret genetic diversity within and among species, we utilized genome sequence data from 78 mammalian species to compare θ and ROH burden (i.e., number and length of ROHs in the genome) among groups of mammals to assess genomic signatures of inbreeding. We compared θ and ROHs: (i) among threatened and non-threatened mammals to determine the significance of contemporary conservation status; (ii) among carnivorous and non-carnivorous mammals to determine the relevance of trophic effects; (iii) relative to body size because mutation rates generally vary with body mass; and (iv) across mammals from different latitudes to test for gradients in genomic diversity (e.g., due to effects of historic climatic regimes). Our results illustrate the considerable variance in genomic diversity across mammals, and that trophic level, body mass, and latitude have significant effects on θ and ROH burden. However, conservation status was not a reliable indicator of genomic diversity. We argue that genetic or genomic diversity should be an explicit component of conservation status, as such diversity is critical to the long-term sustainability of populations, and anticipate that ROHs will become more commonly used to estimate inbreeding in wild animals.

Keywords

Genomic diversity Inbreeding Nucleotide diversity Autozygosity Demographic history Effective population size 

Notes

Acknowledgements

We thank Anders Albrechtsen for helpful comments and suggestions to the SNV calling pipeline, and members of the DeWoody lab group for constructive criticism on an earlier version of the manuscript. This work was conducted as a part of the “Next generation genetic monitoring” Working Group at the National Institute for Mathematical and Biological Synthesis, sponsored by the National Science Foundation through NSF Award #DBI-1300426, with additional support from The University of Tennessee, Knoxville.

Supplementary material

10592_2018_1099_MOESM1_ESM.docx (1.3 mb)
Supplementary material 1 (DOCX 1377 KB)

References

  1. Adams RI, Hadly EA (2013) Genetic diversity within vertebrate species is greater at lower latitudes. Evol Ecol 27:133–143CrossRefGoogle Scholar
  2. Ashton KG, Tracy MC, Queiroz Ad (2000) Is Bergmann’s rule valid for mammals? Am Nat 156:390–415PubMedGoogle Scholar
  3. Auwera GA, Carneiro MO, Hartl C, Poplin R, del Angel G, Levy-Moonshine A, Jordan T, Shakir K, Roazen D, Thibault J (2013) From FastQ data to high-confidence variant calls: the genome analysis toolkit best practices pipeline. Curr Protoc Bioinform 43:11.10.1−11.10.33Google Scholar
  4. Bentley DR, Balasubramanian S, Swerdlow HP, Smith GP, Milton J, Brown CG, Hall KP, Evers DJ, Barnes CL, Bignell HR, Boutell JM, Bryant J, Carter RJ, Keira Cheetham R, Cox AJ, Ellis DJ, Flatbush MR, Gormley NA, Humphray SJ, Irving LJ, Karbelashvili MS, Kirk SM, Li H, Liu X, Maisinger KS, Murray LJ, Obradovic B, Ost T, Parkinson ML, Pratt MR, Rasolonjatovo IMJ, Reed MT, Rigatti R, Rodighiero C, Ross MT, Sabot A, Sankar SV, Scally A, Schroth GP, Smith ME, Smith VP, Spiridou A, Torrance PE, Tzonev SS, Vermaas EH, Walter K, Wu X, Zhang L, Alam MD, Anastasi C, Aniebo IC, Bailey DMD, Bancarz IR, Banerjee S, Barbour SG, Baybayan PA, Benoit VA, Benson KF, Bevis C, Black PJ, Boodhun A, Brennan JS, Bridgham JA, Brown RC, Brown AA, Buermann DH, Bundu AA, Burrows JC, Carter NP, Castillo N, Catenazzi M, Chang S, Neil Cooley R, Crake NR, Dada OO, Diakoumakos KD, Dominguez-Fernandez B, Earnshaw DJ, Egbujor UC, Elmore DW, Etchin SS, Ewan MR, Fedurco M, Fraser LJ, Fuentes Fajardo KV, Scott Furey W, George D, Gietzen KJ, Goddard CP, Golda GS, Granieri PA, Green DE, Gustafson DL, Hansen NF, Harnish K, Haudenschild CD, Heyer NI, Hims MM, Ho JT, Horgan AM, Hoschler K, Hurwitz S, Ivanov DV, Johnson MQ, James T, Huw Jones TA, Kang G-D, Kerelska TH, Kersey AD, Khrebtukova I, Kindwall AP, Kingsbury Z, Kokko-Gonzales PI, Kumar A, Laurent MA, Lawley CT, Lee SE, Lee X, Liao AK, Loch JA, Lok M, Luo S, Mammen RM, Martin JW, McCauley PG, McNitt P, Mehta P, Moon KW, Mullens JW, Newington T, Ning Z, Ling Ng B, Novo SM, O/‘Neill MJ, Osborne MA, Osnowski A, Ostadan O, Paraschos LL, Pickering L, Pike AC, Pike AC, Chris Pinkard D, Pliskin DP, Podhasky J, Quijano VJ, Raczy C, Rae VH, Rawlings SR, Chiva Rodriguez A, Roe PM, Rogers J, Rogert Bacigalupo MC, Romanov N, Romieu A, Roth RK, Rourke NJ, Ruediger ST, Rusman E, Sanches-Kuiper RM, Schenker MR, Seoane JM, Shaw RJ, Shiver MK, Short SW, Sizto NL, Sluis JP, Smith MA, Ernest SSJ, Spence EJ, Stevens K, Sutton N, Szajkowski L, Tregidgo CL, Turcatti G, vande Vondele S, Verhovsky Y, Virk SM, Wakelin S, Walcott GC, Wang J, Worsley GJ, Yan J, Yau L, Zuerlein M, Rogers J, Mullikin JC, Hurles ME, McCooke NJ, West JS, Oaks FL, Lundberg PL, Klenerman D, Durbin R, Smith AJ (2008) Accurate whole human genome sequencing using reversible terminator chemistry. Nature 456:53–59CrossRefGoogle Scholar
  5. Bosse M, Megens H-J, Madsen O, Paudel Y, Frantz LAF, Schook LB, Crooijmans RPMA, Groenen MAM (2012) Regions of homozygosity in the porcine genome: consequence of demography and the recombination landscape. PLoS Genet, 8, e1003100CrossRefGoogle Scholar
  6. Bromham L (2011) The genome as a life-history character: why rate of molecular evolution varies between mammal species. Philos Trans R Soc Lond B Biol Sci 366:2503–2513CrossRefGoogle Scholar
  7. Bromham L, Rambaut A, Harvey PH (1996) Determinants of rate variation in mammalian DNA sequence evolution. J Mol Evol 43:610–621CrossRefGoogle Scholar
  8. Cardillo M, Mace GM, Jones KE, Bielby J, Bininda-Emonds ORP, Sechrest W, Orme CDL, Purvis A (2005) Multiple causes of high extinction risk in large mammal species. Science 309:1239–1241CrossRefGoogle Scholar
  9. Ceballos G, Ehrlich PR, Barnosky AD, García A, Pringle RM, Palmer TM (2015) Accelerated modern human–induced species losses: entering the sixth mass extinction. Sci Adv 1:e1400253CrossRefGoogle Scholar
  10. Chao L, Carr DE (1993) The molecular clock and the relationship between population size and generation time. Evolution 47:688–690CrossRefGoogle Scholar
  11. Corbett-Detig RB, Hartl DL, Sackton TB (2015) Natural selection constrains neutral diversity across a wide range of species. PLoS Biol 13:e1002112CrossRefGoogle Scholar
  12. Creel S, Spong G, Creel N (2001) Interspecific competition and the population biology of extinction-prone carnivores. Wayne RK, Funk SM, Gittleman J, Macdonald D (eds) Carnivore conservation, Conservation Biology Series. Cambridge University Press, Cambridge, pp 35–60Google Scholar
  13. DePristo MA, Banks E, Poplin R, Garimella KV, Maguire JR, Hartl C, Philippakis AA, Del Angel G, Rivas MA, Hanna M (2011) A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat Genet 43:491–498CrossRefGoogle Scholar
  14. DeWoody J, Avise J (2000) Microsatellite variation in marine, freshwater and anadromous fishes compared with other animals. J Fish Biol 56:461–473CrossRefGoogle Scholar
  15. DeWoody YD, DeWoody JA (2005) On the estimation of genome-wide heterozygosity using molecular markers. J Hered 96:85–88CrossRefGoogle Scholar
  16. Dowle E, Morgan-Richards M, Trewick S (2013) Molecular evolution and the latitudinal biodiversity gradient. Heredity 110:501CrossRefGoogle Scholar
  17. Doyle JM, Hacking CC, Willoughby JR, Sundaram M, DeWoody JA (2015) Mammalian genetic diversity as a function of habitat, body size, trophic class, and conservation status. J Mammal 96:564–572CrossRefGoogle Scholar
  18. Ellegren H (2004) Microsatellites: simple sequences with complex evolution. Nat Rev Genet 5:435–445CrossRefGoogle Scholar
  19. Ellegren H (2014) Genome sequencing and population genomics in non-model organisms. Trends Ecol Evol 29:51–63CrossRefGoogle Scholar
  20. Fan Z, Silva P, Gronau I, Wang S, Armero AS, Schweizer RM, Ramirez O, Pollinger J, Galaverni M, Ortega Del-Vecchyo D, Du L, Zhang W, Zhang Z, Xing J, Vilà C, Marques-Bonet T, Godinho R, Yue B, Wayne RK (2016) Worldwide patterns of genomic variation and admixture in gray wolves. Genome Res 26:163–173CrossRefGoogle Scholar
  21. Ferenčaković M, Sölkner J, Curik I (2013) Estimating autozygosity from high-throughput information: effects of SNP density and genotyping errors. Genet Sel Evol 45:42CrossRefGoogle Scholar
  22. Fischer MC, Rellstab C, Leuzinger M, Roumet M, Gugerli F, Shimizu KK, Holderegger R, Widmer A (2017) Estimating genomic diversity and population differentiation—an empirical comparison of microsatellite and SNP variation in Arabidopsis halleri. BMC Genom 18:69CrossRefGoogle Scholar
  23. Frankham R (1995) Effective population size adult population size ratios in wildlife—a review. Genet Res 66:95–107CrossRefGoogle Scholar
  24. Frankham R (1996) Relationship of genetic variation to population size in wildlife. Conserv Biol 10:1500–1508CrossRefGoogle Scholar
  25. Frankham R (2005) Genetics and extinction. Biol Conserv 126:131–140CrossRefGoogle Scholar
  26. Fraser CI, Nikula R, Ruzzante DE, Waters JM (2012) Poleward bound: biological impacts of Southern Hemisphere glaciation. Trends Ecol Evol 27:462–471CrossRefGoogle Scholar
  27. Garza JC, Williamson EG (2001) Detection of reduction in population size using data from microsatellite loci. Mol Ecol 10:305–318CrossRefGoogle Scholar
  28. Haasl RJ, Payseur BA (2013) Microsatellites as targets of natural selection. Mol Biol Evol 30:285–298CrossRefGoogle Scholar
  29. Hewitt GM (2004) Genetic consequences of climatic oscillations in the Quaternary. Philos Trans R Soc Lond B 359:183–195CrossRefGoogle Scholar
  30. Howrigan DP, Simonson MA, Keller MC (2011) Detecting autozygosity through runs of homozygosity: a comparison of three autozygosity detection algorithms. BMC Genom 12:460–460CrossRefGoogle Scholar
  31. IUCN (2017) The IUCN red list of threatened species. http://www.iucnredlist.org/apps/redlist/details/40540/0. Accessed 01 July 2017
  32. Kardos M, Luikart G, Allendorf FW (2015) Measuring individual inbreeding in the age of genomics: marker-based measures are better than pedigrees. Heredity 115:63–72CrossRefGoogle Scholar
  33. Kardos M, Qvarnström A, Ellegren H (2017) Inferring individual inbreeding and demographic history from segments of identity by descent in Ficedula flycatcher genome sequences. Genetics.  https://doi.org/10.1534/genetics.116.198861 CrossRefPubMedPubMedCentralGoogle Scholar
  34. Keller LF, Waller DM (2002) Inbreeding effects in wild populations. Trends Ecol Evol 17:230–241CrossRefGoogle Scholar
  35. Kimura M (1984) The neutral theory of molecular evolution. Cambridge University Press, CambridgeGoogle Scholar
  36. Kirin M, McQuillan R, Franklin CS, Campbell H, McKeigue PM, Wilson JF (2010) Genomic runs of homozygosity record population history and consanguinity. PLoS ONE 5:e13996CrossRefGoogle Scholar
  37. Levinsky I, Araújo Miguel B, Nogués-Bravo D, Haywood Alan M, Valdes Paul J, Rahbek C (2013) Climate envelope models suggest spatio-temporal co-occurrence of refugia of African birds and mammals. Global Ecol Biogeogr 22:351–363CrossRefGoogle Scholar
  38. Li H, Durbin R (2010) Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics 26:589–595CrossRefGoogle Scholar
  39. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R (2009) The sequence alignment/map format and SAMtools. Bioinformatics 25:2078–2079CrossRefGoogle Scholar
  40. Li H, Xiang-Yu J, Dai G, Gu Z, Ming C, Yang Z, Ryder OA, Li W-H, Fu Y-X, Zhang Y-P (2016) Large numbers of vertebrates began rapid population decline in the late 19th century. PNAS 113:14079–14084CrossRefGoogle Scholar
  41. Malécot G (1948) Mathematics of heredity. Freeman, San FranciscoGoogle Scholar
  42. Martin AP, Palumbi SR (1993) Body size, metabolic rate, generation time, and the molecular clock. PNAS 90:4087–4091CrossRefGoogle Scholar
  43. McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, Garimella K, Altshuler D, Gabriel S, Daly M (2010) The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res 20:1297–1303CrossRefGoogle Scholar
  44. McQuillan R, Leutenegger A-L, Abdel-Rahman R, Franklin CS, Pericic M, Barac-Lauc L, Smolej-Narancic N, Janicijevic B, Polasek O, Tenesa A (2008) Runs of homozygosity in European populations. Am J Hum Genet 83:359–372CrossRefGoogle Scholar
  45. Meynert AM, Ansari M, FitzPatrick DR, Taylor MS (2014) Variant detection sensitivity and biases in whole genome and exome sequencing. BMC Bioinform 15:247CrossRefGoogle Scholar
  46. Miraldo A, Li S, Borregaard MK, Flórez-Rodríguez A, Gopalakrishnan S, Rizvanovic M, Wang Z, Rahbek C, Marske KA, Nogués-Bravo D (2016) An Anthropocene map of genetic diversity. Science 353:1532–1535CrossRefGoogle Scholar
  47. Nielsen R, Paul JS, Albrechtsen A, Song YS (2011) Genotype and SNP calling from next-generation sequencing data. Nat Rev Genet 12:443CrossRefGoogle Scholar
  48. Nielsen R, Korneliussen T, Albrechtsen A, Li Y, Wang J (2012) SNP calling, genotype calling, and sample allele frequency estimation from new-generation sequencing data. PLoS ONE, 7:e37558CrossRefGoogle Scholar
  49. Pacifici M, Santini L, Di Marco M, Baisero D, Francucci L, Marasini GG, Visconti P, Rondinini C (2013) Generation length for mammals. Nat Conserv 5:87–94Google Scholar
  50. Palsbøll PJ, Zachariah Peery M, Olsen MT, Beissinger SR, Bérubé M (2012) Inferring recent historic abundance from current genetic diversity. Mol Ecol 22:22–40CrossRefGoogle Scholar
  51. Parmesan C, Yohe G (2003) A globally coherent fingerprint of climate change impacts across natural systems. Nature 421:37CrossRefGoogle Scholar
  52. Peery MZ, Kirby R, Reid BN, Stoelting R, Doucet-BËEr E, Robinson S, VÁSquez-Carrillo C, Pauli JN, Palsbøll PJ (2012) Reliability of genetic bottleneck tests for detecting recent population declines. Mol Ecol 21:3403–3418CrossRefGoogle Scholar
  53. Peters RH, Raelson JV (1984) Relations between individual size and mammalian population density. Am Nat 124:498–517CrossRefGoogle Scholar
  54. Primm SA, Clark TW (1996) Making sense of the policy process for carnivore conservation. Conserv Biol 10:1036–1045CrossRefGoogle Scholar
  55. Provan J, Bennett KD (2008) Phylogeographic insights into cryptic glacial refugia. Trends Ecol Evol 23:564–571CrossRefGoogle Scholar
  56. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira M, Bender D, Maller J, Sklar P, de Bakker P, Daly M, Sham P (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81:559–575CrossRefGoogle Scholar
  57. Pusey A, Wolf M (1996) Inbreeding avoidance in animals. Trends Ecol Evol 11:201–206CrossRefGoogle Scholar
  58. Ralls K, Ballou JD, Dudash MR, Eldridge MD, Fenster CB, Lacy RC, Sunnucks P, Frankham R (2017) Call for a paradigm shift in the genetic management of fragmented populations. Conserv Lett 11(2):e12412CrossRefGoogle Scholar
  59. Robinson JG, Redford KH (1986) Body size, diet, and population density of neotropical forest mammals. Am Nat 128:665–680CrossRefGoogle Scholar
  60. Romiguier J, Gayral P, Ballenghien M, Bernard A, Cahais V, Chenuil A, Chiari Y, Dernat R, Duret L, Faivre N, Loire E, Lourenco JM, Nabholz B, Roux C, Tsagkogeorga G, Weber AAT, Weinert LA, Belkhir K, Bierne N, Glemin S, Galtier N (2014) Comparative population genomics in animals uncovers the determinants of genetic diversity. Nature 515:261–263CrossRefGoogle Scholar
  61. Rondinini C, Di Marco M, Chiozza F, Santulli G, Baisero D, Visconti P, Hoffmann M, Schipper J, Stuart SN, Tognelli MF, Amori G, Falcucci A, Maiorano L, Boitani L (2011) Global habitat suitability models of terrestrial mammals. Philos Trans R Soc Lond B 366:2633–2641CrossRefGoogle Scholar
  62. Schubert M, Lindgreen S, Orlando L (2016) AdapterRemoval v2: rapid adapter trimming, identification, and read merging. BMC Res Notes 9:88CrossRefGoogle Scholar
  63. Spielman D, Brook BW, Frankham R (2004) Most species are not driven to extinction before genetic factors impact them. PNAS 101:15261–15264CrossRefGoogle Scholar
  64. Sterck EH, Willems EP, van Hooff JA, Wich SA (2005) Female dispersal, inbreeding avoidance and mate choice in Thomas langurs (Presbytis thomasi). Behaviour 142:845–868CrossRefGoogle Scholar
  65. Team RDC (2017) R: A language and environment for statistical computing. Team RDC, ViennaGoogle Scholar
  66. Vellend M, Lajoie G, Bourret A, Múrria C, Kembel SW, Garant D (2014) Drawing ecological inferences from coincident patterns of population-and community-level biodiversity. Mol Ecol 23:2890–2901CrossRefGoogle Scholar
  67. Walther G-R, Post E, Convey P, Menzel A, Parmesan C, Beebee TJC, Fromentin J-M, Hoegh-Guldberg O, Bairlein F (2002) Ecological responses to recent climate change. Nature 416:389–395CrossRefGoogle Scholar
  68. Weir B, Cockerham C (1984) Estimating F-statistics for the analysis of population structure. Evolution 38:1358–1370PubMedGoogle Scholar
  69. Weir JT, Schluter D (2011) Are rates of molecular evolution in mammals substantially accelerated in warmer environments? Proc R Soc Lond B Biol Sci 278:1291–1293CrossRefGoogle Scholar
  70. Willoughby JR, Sundaram M, Wijayawardena BK, Kimble SJA, Ji Y, Fernandez NB, Antonides JD, Lamb MC, Marra NJ, DeWoody JA (2015) The reduction of genetic diversity in threatened vertebrates and new recommendations regarding IUCN conservation rankings. Biol Conserv 191:495–503CrossRefGoogle Scholar
  71. Wright S (1922) Coefficients of inbreeding and relationship. Am Nat 56:330–338CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2018
corrected publication September/2018

Authors and Affiliations

  1. 1.Department of Forestry & Natural ResourcesPurdue UniversityWest LafayetteUSA
  2. 2.Department of Biological SciencesPurdue UniversityWest LafayetteUSA

Personalised recommendations