Advances in Quantitative Trait Analysis in Yeast
Understanding the genetic mechanisms underlying complex traits is one of the next frontiers in biology. The budding yeast Saccharomyces cerevisiae has become an important model for elucidating the mechanisms that govern natural genetic and phenotypic variation. This success is partially due to its intrinsic biological features, such as the short sexual generation time, high meiotic recombination rate, and small genome size. Precise reverse genetics technologies allow the high throughput manipulation of genetic information with exquisite precision, offering the unique opportunity to experimentally measure the phenotypic effect of genetic variants. Population genomic and phenomic studies have revealed widespread variation between diverged populations, characteristic of man-made environments, as well as geographic clusters of wild strains along with naturally occurring recombinant strains (mosaics). Here, we review these recent studies and provide a perspective on how these previously unappreciated levels of variation can help to bridge our understanding of the genotype-phenotype gap, keeping budding yeast at the forefront of genetic studies. Not only are quantitative trait loci (QTL) being mapped with high resolution down to the nucleotide, for the first time QTLs of modest effect and complex interactions between these QTLs and between QTLs and the environment are being determined experimentally at unprecedented levels using next generation techniques of deep sequencing selected pools of individuals as well as multi-generational crosses.
Vyšlo v časopise:
Advances in Quantitative Trait Analysis in Yeast. PLoS Genet 8(8): e32767. doi:10.1371/journal.pgen.1002912
Kategorie:
Review
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1002912
Souhrn
Understanding the genetic mechanisms underlying complex traits is one of the next frontiers in biology. The budding yeast Saccharomyces cerevisiae has become an important model for elucidating the mechanisms that govern natural genetic and phenotypic variation. This success is partially due to its intrinsic biological features, such as the short sexual generation time, high meiotic recombination rate, and small genome size. Precise reverse genetics technologies allow the high throughput manipulation of genetic information with exquisite precision, offering the unique opportunity to experimentally measure the phenotypic effect of genetic variants. Population genomic and phenomic studies have revealed widespread variation between diverged populations, characteristic of man-made environments, as well as geographic clusters of wild strains along with naturally occurring recombinant strains (mosaics). Here, we review these recent studies and provide a perspective on how these previously unappreciated levels of variation can help to bridge our understanding of the genotype-phenotype gap, keeping budding yeast at the forefront of genetic studies. Not only are quantitative trait loci (QTL) being mapped with high resolution down to the nucleotide, for the first time QTLs of modest effect and complex interactions between these QTLs and between QTLs and the environment are being determined experimentally at unprecedented levels using next generation techniques of deep sequencing selected pools of individuals as well as multi-generational crosses.
Zdroje
1. BarnettJA (2007) A history of research on yeasts 10: foundations of yeast genetics. Yeast 24: 799–845.
2. MackayTF, StoneEA, AyrolesJF (2009) The genetics of quantitative traits: challenges and prospects. Nat Rev Genet 10: 565–577.
3. NieduszynskiCA, LitiG (2011) From sequence to function: insights from natural variation in budding yeasts. Biochim Biophys Acta 1810: 959–966.
4. BremRB, YvertG, ClintonR, KruglyakL (2002) Genetic dissection of transcriptional regulation in budding yeast. Science 296: 752–755.
5. SteinmetzLM, SinhaH, RichardsDR, SpiegelmanJI, OefnerPJ, et al. (2002) Dissecting the architecture of a quantitative trait locus in yeast. Nature 416: 326–330.
6. YvertG, BremRB, WhittleJ, AkeyJM, FossE, et al. (2003) Trans-acting regulatory variation in Saccharomyces cerevisiae and the role of transcription factors. Nat Genet 35: 57–64.
7. BlandinSA, Wang-SattlerR, LamacchiaM, GagneurJ, LycettG, et al. (2009) Dissecting the genetic basis of resistance to malaria parasites in Anopheles gambiae. Science 326: 147–150.
8. GerkeJ, LorenzK, CohenB (2009) Genetic interactions between transcription factors cause natural variation in yeast. Science 323: 498–501.
9. FayJC, BenavidesJA (2005) Evidence for domesticated and wild populations of Saccharomyces cerevisiae. PLoS Genet 1: e5 doi:10.1371/journal.pgen.0010005.
10. LegrasJL, MerdinogluD, CornuetJM, KarstF (2007) Bread, beer and wine: Saccharomyces cerevisiae diversity reflects human history. Mol Ecol 16: 2091–2102.
11. SampaioJP, GoncalvesP (2008) Natural populations of Saccharomyces kudriavzevii in Portugal are associated with oak bark and are sympatric with S. cerevisiae and S. paradoxus. Appl Environ Microbiol 74: 2144–2152.
12. SniegowskiPD, DombrowskiPG, FingermanE (2002) Saccharomyces cerevisiae and Saccharomyces paradoxus coexist in a natural woodland site in North America and display different levels of reproductive isolation from European conspecifics. FEMS Yeast Res 1: 299–306.
13. LitiG, CarterDM, MosesAM, WarringerJ, PartsL, et al. (2009) Population genomics of domestic and wild yeasts. Nature 458: 337–341.
14. CubillosFA, BilliE, ZorgoE, PartsL, FargierP, et al. (2011) Assessing the complex architecture of polygenic traits in diverged yeast populations. Mol Ecol 20: 1401–1413.
15. KimHS, FayJC (2007) Genetic variation in the cysteine biosynthesis pathway causes sensitivity to pharmacological compounds. Proc Natl Acad Sci U S A 104: 19387–19391.
16. LitiG, HaricharanS, CubillosFA, TierneyAL, SharpS, et al. (2009) Segregating YKU80 and TLC1 alleles underlying natural variation in telomere properties in wild yeast. PLoS Genet 5: e1000659 doi:10.1371/journal.pgen.1000659.
17. SeidelHS, RockmanMV, KruglyakL (2008) Widespread genetic incompatibility in C. elegans maintained by balancing selection. Science 319: 589–594.
18. LehnerB (2011) Molecular mechanisms of epistasis within and between genes. Trends Genet 27: 323–331.
19. SinhaH, NicholsonBP, SteinmetzLM, McCuskerJH (2006) Complex genetic interactions in a quantitative trait locus. PLoS Genet 2: e13 doi:10.1371/journal.pgen.0020013.
20. LibudaDE, WinstonF (2006) Amplification of histone genes by circular chromosome formation in Saccharomyces cerevisiae. Nature 443: 1003–1007.
21. DowellRD, RyanO, JansenA, CheungD, AgarwalaS, et al. (2010) Genotype to phenotype: a complex problem. Science 328: 469.
22. GranekJA, MagwenePM (2010) Environmental and genetic determinants of colony morphology in yeast. PLoS Genet 6: e1000823 doi:10.1371/journal.pgen.1000823.
23. SmithJJ, MillerLR, KreisbergR, VazquezL, WanY, et al. (2011) Environment-responsive transcription factors bind subtelomeric elements and regulate gene silencing. Mol Syst Biol 7: 455.
24. JaroszDF, LindquistS (2010) Hsp90 and environmental stress transform the adaptive value of natural genetic variation. Science 330: 1820–1824.
25. NagarajanM, VeyrierasJB, de DieuleveultM, BottinH, FehrmannS, et al. (2010) Natural single-nucleosome epi-polymorphisms in yeast. PLoS Genet 6: e1000913 doi:10.1371/journal.pgen.1000913.
26. Ben-AriG, ZenvirthD, ShermanA, DavidL, KlutsteinM, et al. (2006) Four linked genes participate in controlling sporulation efficiency in budding yeast. PLoS Genet 2: e195 doi:10.1371/journal.pgen.0020195.
27. DeutschbauerAM, DavisRW (2005) Quantitative trait loci mapped to single-nucleotide resolution in yeast. Nat Genet 37: 1333–1340.
28. SwinnenS, SchaerlaekensK, PaisT, ClaesenJ, HubmannG, et al. (2012) Identification of novel causative genes determining the complex trait of high ethanol tolerance in yeast using pooled-segregant whole-genome sequence analysis. Genome Research 22: 975–984.
29. KroymannJ, Mitchell-OldsT (2005) Epistasis and balanced polymorphism influencing complex trait variation. Nature 435: 95–98.
30. JoronM, FrezalL, JonesRT, ChamberlainNL, LeeSF, et al. (2011) Chromosomal rearrangements maintain a polymorphic supergene controlling butterfly mimicry. Nature 477: 203–206.
31. ZiaA, MosesAM (2011) Ranking insertion, deletion and nonsense mutations based on their effect on genetic information. BMC Bioinformatics 12: 299.
32. WarringerJ, ZorgoE, CubillosFA, ZiaA, GjuvslandA, et al. (2011) Trait variation in yeast is defined by population history. PLoS Genet 7: e1002111 doi:10.1371/journal.pgen.1002111.
33. BrachiB, MorrisGP, BorevitzJO (2011) Genome-wide association studies in plants: the missing heritability is in the field. Genome Biology 12: 232.
34. SchachererJ, ShapiroJA, RuderferDM, KruglyakL (2009) Comprehensive polymorphism survey elucidates population structure of Saccharomyces cerevisiae. Nature 458: 342–345.
35. AmbrosetC, PetitM, BrionC, SanchezI, DelobelP, et al. (2011) Deciphering the molecular basis of wine yeast fermentation traits using a combined genetic and genomic approach. G3 1: 263–281.
36. AnselJ, BottinH, Rodriguez-BeltranC, DamonC, NagarajanM, et al. (2008) Cell-to-cell stochastic variation in gene expression is a complex genetic trait. PLoS Genet 4: e1000049 doi:10.1371/journal.pgen.1000049.
37. DemoginesA, SmithE, KruglyakL, AlaniE (2008) Identification and dissection of a complex DNA repair sensitivity phenotype in Baker's yeast. PLoS Genet 4: e1000123 doi:10.1371/journal.pgen.1000123.
38. MarulloP, AigleM, BelyM, Masneuf-PomaredeI, DurrensP, et al. (2007) Single QTL mapping and nucleotide-level resolution of a physiologic trait in wine Saccharomyces cerevisiae strains. FEMS Yeast Research 7: 941–952.
39. NogamiS, OhyaY, YvertG (2007) Genetic complexity and quantitative trait loci mapping of yeast morphological traits. PLoS Genet 3: e31 doi:10.1371/journal.pgen.0030031.
40. RomanoGH, GurvichY, LaviO, UlitskyI, ShamirR, et al. (2010) Different sets of QTLs influence fitness variation in yeast. Mol Syst Biol 6: 346.
41. SinhaH, DavidL, PasconRC, Clauder-MunsterS, KrishnakumarS, et al. (2008) Sequential elimination of major-effect contributors identifies additional quantitative trait loci conditioning high-temperature growth in yeast. Genetics 180: 1661–1670.
42. EhrenreichIM, BloomJ, TorabiN, WangX, JiaY, et al. (2012) Genetic architecture of highly complex chemical resistance traits across four yeast strains. PLoS Genet 8: e1002570 doi:10.1371/journal.pgen.1002570.
43. EhrenreichIM, TorabiN, JiaY, KentJ, MartisS, et al. (2010) Dissection of genetically complex traits with extremely large pools of yeast segregants. Nature 464: 1039–1042.
44. PartsL, CubillosFA, WarringerJ, JainK, SalinasF, et al. (2011) Revealing the genetic structure of a trait by sequencing a population under selection. Genome Res 21: 1131–1138.
45. SegreAV, MurrayAW, LeuJY (2006) High-resolution mutation mapping reveals parallel experimental evolution in yeast. PLoS Biol 4: e256 doi:10.1371/journal.pbio.0040256.
46. WengerJW, SchwartzK, SherlockG (2010) Bulk segregant analysis by high-throughput sequencing reveals a novel xylose utilization gene from Saccharomyces cerevisiae. PLoS Genet 6: e1000942 doi:10.1371/journal.pgen.1000942.
47. DymondJS, RichardsonSM, CoombesCE, BabatzT, MullerH, et al. (2011) Synthetic chromosome arms function in yeast and generate phenotypic diversity by design. Nature 477: 471–476.
48. JelierR, SempleJI, Garcia-VerdugoR, LehnerB (2011) Predicting phenotypic variation in yeast from individual genome sequences. Nat Genet 43: 1270–1274.
49. TimberlakeWE, FrizzellMA, RichardsKD, GardnerRC (2011) A new yeast genetic resource for analysis and breeding. Yeast 28: 63–80.
50. ZorgoE, GjuvslandA, CubillosFA, LouisEJ, LitiG, et al. (2012) Life history shapes trait heredity by promoting accumulation of loss-of-function alleles in yeast. Mol Biol Evol
51. MagwenePM, KayikciO, GranekJA, ReiningaJM, SchollZ, et al. (2011) Outcrossing, mitotic recombination, and life-history trade-offs shape genome evolution in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 108: 1987–1992.
52. TurnerTL, StewartAD, FieldsAT, RiceWR, TaroneAM (2011) Population-based resequencing of experimentally evolved populations reveals the genetic basis of body size variation in Drosophila melanogaster. PLoS Genet 7: e1001336 doi:10.1371/journal.pgen.1001336.
53. CookRK, ChristensenSJ, DealJA, CoburnRA, DealME, et al. (2012) The generation of chromosomal deletions to provide extensive coverage and subdivision of the Drosophila melanogaster genome. Genome Biology 13: R21.
54. ManolioTA, CollinsFS, CoxNJ, GoldsteinDB, HindorffLA, et al. (2009) Finding the missing heritability of complex diseases. Nature 461: 747–753.
55. HietpasRT, JensenJD, BolonDN (2011) Experimental illumination of a fitness landscape. Proc Natl Acad Sci U S A 108: 7896–7901.
56. IllingworthCJ, PartsL, SchiffelsS, LitiG, MustonenV (2011) Quantifying selection acting on a complex trait using allele frequency time-series data. Mol Biol Evol 29: 1187–1197.
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2012 Číslo 8
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
Najčítanejšie v tomto čísle
- Dissecting the Gene Network of Dietary Restriction to Identify Evolutionarily Conserved Pathways and New Functional Genes
- It's All in the Timing: Too Much E2F Is a Bad Thing
- Variation of Contributes to Dog Breed Skull Diversity
- The PARN Deadenylase Targets a Discrete Set of mRNAs for Decay and Regulates Cell Motility in Mouse Myoblasts