title: Strong mutational bias toward deletions in the Drosophila melanogaster genome is compensated by selection.
abstract: Insertions and deletions (collectively indels) obviously have a major impact on genome evolution. However, before large-scale data on indel polymorphism became available, it was difficult to estimate the strength of selection acting on indel mutations. Here, we analyze indel polymorphism and divergence in different compartments of the Drosophila melanogaster genome: exons, introns of different lengths, and intergenic regions. Data on low-frequency polymorphisms indicate that 0.036-0.039 short (1-30 nt) insertion mutations and 0.085-0.092 short deletion mutations, with mean lengths 3.23 and 4.78, respectively, occur per single-nucleotide substitution. The excess of short deletion over short insertion mutations implies that indel mutations of these lengths should lead to a loss of approximately 0.30 nt per single-nucleotide replacement. However, polymorphism and divergence data show that this deletion bias is almost completely compensated by selection: Negative selection is stronger against deletions, whereas insertions are more likely to be favored by positive selection. Among the inframe low-frequency polymorphic mutations in exons, long introns, and intergenic regions, selection prevents a larger fraction of deletions (80-87%, depending on the type of the compartment) than of insertions (70-82%) or single-nucleotide substitutions (49-73%), from reaching high frequencies. The corresponding fractions were the lowest in short introns: 66%, 47%, and 15%, respectively, consistent with the weakest selective constraint in them. The McDonald-Kreitman test shows that 32-46% of the deletions and 60-73% of the insertions that were fixed in the recent evolution of D. melanogaster are adaptive, whereas this fraction is only 0-29% for single-nucleotide substitutions.
authors: Department of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia. leushkin@gmail.com
authors: Evgeny V
authors: EV
authors: Leushkin
authors: Georgii A
authors: GA
authors: Bazykin
authors: Alexey S
authors: AS
authors: Kondrashov
mesh_terms: D000818:Animals; D004331:Drosophila melanogaster / Q000235:genetics*; D019143:Evolution, Molecular; D005091:Exons; D049750:Genome, Insect; D054643:INDEL Mutation; D007438:Introns; D008957:Models, Genetic; D059645:Mutation Rate; D011110:Polymorphism, Genetic; D012641:Selection, Genetic
references: Nature. 1996 Nov 28;384(6607):346-9
references: 8934517
references: Nature. 2007 Jan 4;445(7123):82-5
references: 17203060
references: Mol Biol Evol. 2010 Jun;27(6):1226-34
references: 20150340
references: Nature. 2012 Feb 08;482(7384):173-8
references: 22318601
references: Genetics. 2007 Dec;177(4):2251-61
references: 18073430
references: Genome Biol Evol. 2009 Oct 20;1:415-9
references: 20333210
references: Genetics. 2005 Mar;169(3):1521-7
references: 15654088
references: Nature. 2005 Oct 20;437(7062):1149-52
references: 16237443
references: Genetics. 2009 Aug;182(4):1219-32
references: 19528323
references: Genetics. 1994 Sep;138(1):227-34
references: 8001789
references: J Mol Evol. 2012 Feb;74(1-2):61-8
references: 22327123
references: Mol Biol Evol. 2008 Jun;25(6):1007-15
references: 18195052
references: Nature. 1991 Jun 20;351(6328):652-4
references: 1904993
references: Annu Rev Genet. 2008;42:287-99
references: 18983258
references: Mol Biol Evol. 2005 Sep;22(9):1845-52
references: 15930155
references: Genetics. 2000 Nov;156(3):1175-90
references: 11063693
references: Mol Biol Evol. 2007 Oct;24(10):2222-34
references: 17646256
references: Genome Res. 2010 Sep;20(9):1297-303
references: 20644199
references: J Mol Evol. 2003;57 Suppl 1:S154-64
references: 15008412
references: Mol Biol Evol. 2002 Dec;19(12):2211-25
references: 12446812
references: PLoS One. 2011 Mar 17;6(3):e17945
references: 21437290
references: PLoS Biol. 2007 Nov 6;5(11):e310
references: 17988176
references: Genome Biol. 2007;8(2):R18
references: 17284312
references: BMC Genomics. 2011 May 19;12:245
references: 21592414
references: Genome Res. 2006 Jul;16(7):875-84
references: 16751341
references: Nature. 2007 Nov 8;450(7167):203-18
references: 17994087
references: Genome Biol. 2007;8(7):R143
references: 17659080
references: Genome Res. 2007 Dec;17(12):1837-49
references: 17989258
references: Mol Biol Evol. 1998 Mar;15(3):293-302
references: 9501496
references: Mol Biol Evol. 2007 May;24(5):1190-7
references: 17322553
references: Nature. 2002 Feb 28;415(6875):1022-4
references: 11875568
references: Genetics. 2009 Oct;183(2):651-62, 1SI-23SI
references: 19620398
references: Nat Biotechnol. 2011 Jan;29(1):24-6
references: 21221095
references: Mol Biol Evol. 2009 Sep;26(9):2097-108
references: 19535738
references: J Evol Biol. 2012 Oct;25(10):1975-1990
references: 22901008
references: Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2271-6
references: 17284599
references: Nature. 2002 Feb 28;415(6875):1024-6
references: 11875569
references: Mol Biol Evol. 2006 Nov;23(11):2203-13
references: 16923822
references: Bioinformatics. 2009 Aug 15;25(16):2078-9
references: 19505943
references: J Mol Evol. 2006 Jun;62(6):793-802
references: 16752217
references: BMC Evol Biol. 2007 Nov 15;7:226
references: 18005411
references: Genetics. 2003 Dec;165(4):1843-51
references: 14704170
references: Genetica. 2002 May;115(1):81-91
references: 12188050
references: Nucleic Acids Res. 2007 Jan;35(Database issue):D486-91
references: 17099233
references: Mol Biol Evol. 2004 Jul;21(7):1350-60
references: 15044594
references: Nucleic Acids Res. 2004 Mar 19;32(5):1792-7
references: 15034147