Quantifying the mechanisms for segmental duplications in mammalian genomes by statistical analysis and modeling.
A large number of the segmental duplications in mammalian genomes have been cataloged by genome-wide sequence analyses. The molecular mechanisms involved in these duplications mostly remain a matter of speculation. To uncover, test, and further quantify the hypotheses on the mechanisms for the recent duplications in the mammalian genomes, we have performed a series of statistical analyses on the sequences flanking the duplicated segments and proposed a dynamic model for the duplication process. The model, when applied to the human duplication data, indicates that approximately 30% of the recent human segmental duplications were caused by a recombination-like mechanism, among which 12% were mediated by the most recently active repeat, Alu. But a significant proportion of the duplications are caused by some mechanism independent of the repeat distribution. A less sure but similar picture is found in the rodent genomes. A further analysis on the physical features of the flanking sequences suggests that one of the uncharacterized duplication mechanisms shared by the mammalian genomes is surprisingly well correlated with the physical instability in the DNA sequences.
Zhou
Yi
Y
Department of Biology, New York University, New York, NY 10003, USA.
Mishra
Bud
B
D000818:Animals; D003627:Data Interpretation, Statistical; D019143:Evolution, Molecular; D020440:Gene Duplication; D023281:Genomics; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D051381:Rats; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA
Biochemistry. 1989 Sep 19;28(19):7842-9
2611216
Hum Mol Genet. 2003 Jun 1;12(11):1321-8
12761047
Proc Natl Acad Sci U S A. 1986 Jun;83(11):3746-50
3459152
Genome Biol. 2003;4(4):R25
12702206
Genome Res. 2004 Apr;14(4):493-506
15059990
Genes Chromosomes Cancer. 2002 Oct;35(2):97-112
12203773
Nature. 1998 Dec 17;396(6712):643-9
9872311
J Mol Evol. 1996 Jan;42(1):59-65
8576965
Genome Res. 2000 Nov;10(11):1726-36
11076858
Cancer Genet Cytogenet. 2002 Oct 15;138(2):149-52
12505261
Hum Mol Genet. 1997 Sep;6(9):1513-7
9285788
Genome Biol. 2003;4(8):R47
12914656
Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):8141-6
9653154
Nature. 2004 Oct 21;431(7011):927-30
15496912
Science. 2002 Aug 9;297(5583):1003-7
12169732
Hum Mol Genet. 2003 Sep 1;12(17):2201-8
12915466
J Mol Biol. 1995 Feb 24;246(3):401-417
7877164
Genome Res. 2004 May;14(5):789-801
15123579
Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2999-3003
8385354
EMBO J. 2004 Jan 14;23(1):234-43
14685272
Nat Rev Genet. 2002 May;3(5):370-9
11988762
Nature. 2004 Apr 1;428(6982):493-521
15057822
Genome Res. 2003 Mar;13(3):358-68
12618366
Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):14988-93
14630947
Genome Biol. 2004;5(4):R23
15059256
Genes Chromosomes Cancer. 2003 Nov;38(3):215-25
14506695
Nat Genet. 1999 Sep;23(1):41-6
10471496
Genome Res. 2003 Dec;13(12):2519-32
14656960
Am J Hum Genet. 2003 Oct;73(4):823-34
14505274
Virology. 2004 Oct 25;328(2):282-91
15464848
Mol Biol Evol. 2005 Jan;22(1):135-41
15371527
Nature. 2002 Dec 5;420(6915):520-62
12466850