title: Purifying Selection Maintains Dosage-Sensitive Genes during Degeneration of the Threespine Stickleback Y Chromosome.
abstract: Sex chromosomes are subject to unique evolutionary forces that cause suppression of recombination, leading to sequence degeneration and the formation of heteromorphic chromosome pairs (i.e., XY or ZW). Although progress has been made in characterizing the outcomes of these evolutionary processes on vertebrate sex chromosomes, it is still unclear how recombination suppression and sequence divergence typically occur and how gene dosage imbalances are resolved in the heterogametic sex. The threespine stickleback fish (Gasterosteus aculeatus) is a powerful model system to explore vertebrate sex chromosome evolution, as it possesses an XY sex chromosome pair at relatively early stages of differentiation. Using a combination of whole-genome and transcriptome sequencing, we characterized sequence evolution and gene expression across the sex chromosomes. We uncovered two distinct evolutionary strata that correspond with known structural rearrangements on the Y chromosome. In the oldest stratum, only a handful of genes remain, and these genes are under strong purifying selection. By comparing sex-linked gene expression with expression of autosomal orthologs in an outgroup, we show that dosage compensation has not evolved in threespine sticklebacks through upregulation of the X chromosome in males. Instead, in the oldest stratum, the genes that still possess a Y chromosome allele are enriched for genes predicted to be dosage sensitive in mammals and yeast. Our results suggest that dosage imbalances may have been avoided at haploinsufficient genes by retaining function of the Y chromosome allele through strong purifying selection.
authors.affiliation: Divisions of Human Biology and Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA mawhite@fhcrc.org.
authors.forename: Michael A
authors.initials: MA
authors.lastname: White
authors.affiliation: Ecological Genetics Laboratory, National Institute of Genetics, Shizuoka, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kitano
authors.affiliation: Divisions of Human Biology and Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Peichel
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D018628:Gene Dosage; D008297:Male; D010473:Perciformes / Q000235:genetics*; D012641:Selection, Genetic; D014998:Y Chromosome / Q000235:genetics*
keywords: dosage compensation; sex chromosome evolution; threespine stickleback
references.citation: Science. 1999 Oct 29;286(5441):964-7
references.pmid: 10542153
references.citation: Philos Trans R Soc Lond B Biol Sci. 2000 Nov 29;355(1403):1563-72
references.pmid: 11127901
references.citation: Mol Biol Evol. 2002 Jun;19(6):898-907
references.pmid: 12032246
references.citation: Curr Opin Genet Dev. 2002 Dec;12(6):650-6
references.pmid: 12433577
references.citation: Nature. 2003 Jun 19;423(6942):825-37
references.pmid: 12815422
references.citation: Nature. 2003 Jul 10;424(6945):194-7
references.pmid: 12853957
references.citation: Curr Biol. 2004 Aug 24;14(16):1416-24
references.pmid: 15324658
references.citation: Nature. 2005 Mar 17;434(7031):325-37
references.pmid: 15772651
references.citation: Genetics. 2005 Jun;170(2):975-9
references.pmid: 15834147
references.citation: Heredity (Edinb). 2005 Aug;95(2):118-28
references.pmid: 15931241
references.citation: Nat Rev Genet. 2006 Aug;7(8):645-53
references.pmid: 16847464
references.citation: Curr Opin Genet Dev. 2006 Dec;16(6):578-85
references.pmid: 17055249
references.citation: Evolution. 2006 Sep;60(9):1793-800
references.pmid: 17089964
references.citation: Proc Biol Sci. 2007 Jan 7;274(1606):1-10
references.pmid: 17134994
references.citation: Genetics. 2007 Apr;175(4):1911-21
references.pmid: 17287527
references.citation: Nat Genet. 2007 Mar;39(3):403-8
references.pmid: 17293863
references.citation: Genome Res. 2007 May;17(5):618-24
references.pmid: 17416747
references.citation: Mol Biol Evol. 2007 Aug;24(8):1586-91
references.pmid: 17483113
references.citation: PLoS Comput Biol. 2007 Sep;3(9):1772-82
references.pmid: 17941704
references.citation: Genetics. 2008 Apr;178(4):2045-53
references.pmid: 18245827
references.citation: Nucleic Acids Res. 2008 Jun;36(10):3420-35
references.pmid: 18445632
references.citation: Mol Biol Evol. 2008 Aug;25(8):1639-50
references.pmid: 18477586
references.citation: Nucleic Acids Res. 2008 Sep;36(16):e105
references.pmid: 18660515
references.citation: Genetics. 2008 Aug;179(4):2173-82
references.pmid: 18689886
references.citation: Heredity (Edinb). 2009 Mar;102(3):312-20
references.pmid: 18985062
references.citation: Mol Phylogenet Evol. 2009 Feb;50(2):401-4
references.pmid: 19027080
references.citation: PLoS Genet. 2009 Feb;5(2):e1000391
references.pmid: 19229325
references.citation: Development. 2009 May;136(9):1399-410
references.pmid: 19363150
references.citation: Curr Biol. 2009 Jul 14;19(13):1140-5
references.pmid: 19500990
references.citation: Genome Res. 2009 Jul;19(7):1153-64
references.pmid: 19502380
references.citation: Nature. 2009 Oct 22;461(7267):1079-83
references.pmid: 19783981
references.citation: Evolution. 2010 Mar 1;64(3):663-74
references.pmid: 19796145
references.citation: Bioinformatics. 2010 Jan 1;26(1):139-40
references.pmid: 19910308
references.citation: Trends Genet. 2010 Jan;26(1):15-20
references.pmid: 19963300
references.citation: Science. 1991 Mar 1;251(4997):1030-3
references.pmid: 1998119
references.citation: Nature. 2010 Jan 28;463(7280):536-9
references.pmid: 20072128
references.citation: Mol Biol Evol. 2010 Jul;27(7):1495-503
references.pmid: 20142438
references.citation: BMC Bioinformatics. 2010 Feb 18;11:94
references.pmid: 20167110
references.citation: Genome Biol Evol. 2009 Apr 30;1:56-66
references.pmid: 20333177
references.citation: Genome Res. 2010 Sep;20(9):1297-303
references.pmid: 20644199
references.citation: Mol Phylogenet Evol. 2010 Dec;57(3):978-91
references.pmid: 20723610
references.citation: Mol Ecol. 2010 Sep;19(18):4061-76
references.pmid: 20854276
references.citation: Nat Rev Genet. 2011 Mar;12(3):157-66
references.pmid: 21301475
references.citation: Cytogenet Genome Res. 2011;132(4):219-26
references.pmid: 21307635
references.citation: Nature. 2011 Mar 3;471(7336):115-8
references.pmid: 21368835
references.citation: Nat Genet. 2011 May;43(5):491-8
references.pmid: 21478889
references.citation: Bioinformatics. 2011 Sep 1;27(17):2325-9
references.pmid: 21697122
references.citation: Curr Biol. 2011 Sep 13;21(17):1475-9
references.pmid: 21889890
references.citation: Cytogenet Genome Res. 2011;135(2):150-9
references.pmid: 21921583
references.citation: Trends Genet. 2011 Sep;27(9):358-67
references.pmid: 21962971
references.citation: Bioessays. 2011 Dec;33(12):938-45
references.pmid: 22006834
references.citation: Nature. 2012 Feb 22;483(7387):82-6
references.pmid: 22367542
references.citation: Nat Methods. 2012 Mar 04;9(4):357-9
references.pmid: 22388286
references.citation: Proc Natl Acad Sci U S A. 2012 Apr 3;109(14):5346-51
references.pmid: 22392987
references.citation: Nature. 2012 Apr 04;484(7392):55-61
references.pmid: 22481358
references.citation: PLoS Biol. 2012;10(4):e1001308
references.pmid: 22529744
references.citation: PLoS Biol. 2012;10(5):e1001328
references.pmid: 22615540
references.citation: Proc Natl Acad Sci U S A. 2012 Jul 17;109(29):11752-7
references.pmid: 22753487
references.citation: Proc Natl Acad Sci U S A. 2012 Aug 21;109(34):13710-5
references.pmid: 22869747
references.citation: Mol Ecol. 2013 Feb;22(3):565-82
references.pmid: 22943747
references.citation: Genome Res. 2013 Feb;23(2):300-11
references.pmid: 23275495
references.citation: Nat Rev Genet. 2013 Feb;14(2):113-24
references.pmid: 23329112
references.citation: Proc Natl Acad Sci U S A. 2013 Apr 16;110(16):6453-8
references.pmid: 23547111
references.citation: Mol Ecol. 2013 Jun;22(11):3014-27
references.pmid: 23601112
references.citation: Genome Biol. 2013 Apr 25;14(4):R36
references.pmid: 23618408
references.citation: Genomics. 2013 Oct;102(4):257-64
references.pmid: 23643616
references.citation: J Evol Biol. 2013 Jul;26(7):1417-30
references.pmid: 23663028
references.citation: Genetics. 2013 Jul;194(3):673-86
references.pmid: 23733786
references.citation: Trends Genet. 2013 Sep;29(9):537-44
references.pmid: 23790324
references.citation: Trends Genet. 2013 Dec;29(12):677-83
references.pmid: 23953923
references.citation: PLoS Biol. 2013;11(8):e1001643
references.pmid: 24015111
references.citation: PLoS Genet. 2014 Mar 13;10(3):e1004223
references.pmid: 24625862
references.citation: Nature. 2014 Apr 24;508(7497):488-93
references.pmid: 24759410
references.citation: Nature. 2014 Apr 24;508(7497):494-9
references.pmid: 24759411
references.citation: PLoS Biol. 2014 Jul 01;12(7):e1001899
references.pmid: 24983465
references.citation: Evolution. 2014 Nov;68(11):3281-95
references.pmid: 25066800
references.citation: J Evol Biol. 2014 Jul;27(7):1443-53
references.pmid: 25105198
references.citation: Genome Biol Evol. 2015 Jan 23;7(2):581-90
references.pmid: 25618140
references.citation: Proc Natl Acad Sci U S A. 1978 Nov;75(11):5618-22
references.pmid: 281711
references.citation: Evolution. 1984 Jul;38(4):735-742
references.pmid: 28555827
references.citation: Evolution. 1987 Jul;41(4):911-914
references.pmid: 28564364
references.citation: Genetics. 1987 May;116(1):161-7
references.pmid: 3596229
references.citation: Cytogenetics. 1970;9(5):321-32
references.pmid: 5501390
references.citation: Nature. 1993 Apr 22;362(6422):745-7
references.pmid: 8469284
references.citation: Curr Biol. 1996 Feb 1;6(2):149-62
references.pmid: 8673462