• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of geneticsGeneticsCurrent IssueInformation for AuthorsEditorial BoardSubscribeSubmit a Manuscript
Genetics. Nov 2000; 156(3): 1175–1190.
PMCID: PMC1461334

The correlation between intron length and recombination in drosophila. Dynamic equilibrium between mutational and selective forces.

Abstract

Intron length is negatively correlated with recombination in both Drosophila melanogaster and humans. This correlation is not likely to be the result of mutational processes alone: evolutionary analysis of intron length polymorphism in D. melanogaster reveals equivalent ratios of deletion to insertion in regions of high and low recombination. The polymorphism data do reveal, however, an excess of deletions relative to insertions (i.e., a deletion bias), with an overall deletion-to-insertion events ratio of 1.35. We propose two types of selection favoring longer intron lengths. First, the natural mutational bias toward deletion must be opposed by strong selection in very short introns to maintain the minimum intron length needed for the intron splicing reaction. Second, selection will favor insertions in introns that increase recombination between mutations under the influence of selection in adjacent exons. Mutations that increase recombination, even slightly, will be selectively favored because they reduce interference among selected mutations. Interference selection acting on intron length mutations must be very weak, as indicated by frequency spectrum analysis of Drosophila intron length polymorphism, making the equilibrium for intron length sensitive to changes in the recombinational environment and population size. One consequence of this sensitivity is that the advantage of longer introns is expected to decrease inversely with the rate of recombination, thus leading to a negative correlation between intron length and recombination rate. Also in accord with this model, intron length differs between closely related Drosophila species, with the longest variant present more often in D. melanogaster than in D. simulans. We suggest that the study of the proposed dynamic model, taking into account interference among selected sites, might shed light on many aspects of the comparative biology of genome sizes including the C value paradox.

Full Text

The Full Text of this article is available as a PDF (295K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Akashi H. Inferring weak selection from patterns of polymorphism and divergence at "silent" sites in Drosophila DNA. Genetics. 1995 Feb;139(2):1067–1076. [PMC free article] [PubMed]
  • Akashi H. Molecular evolution between Drosophila melanogaster and D. simulans: reduced codon bias, faster rates of amino acid substitution, and larger proteins in D. melanogaster. Genetics. 1996 Nov;144(3):1297–1307. [PMC free article] [PubMed]
  • Akashi H. Inferring the fitness effects of DNA mutations from polymorphism and divergence data: statistical power to detect directional selection under stationarity and free recombination. Genetics. 1999 Jan;151(1):221–238. [PMC free article] [PubMed]
  • Akashi H, Schaeffer SW. Natural selection and the frequency distributions of "silent" DNA polymorphism in Drosophila. Genetics. 1997 May;146(1):295–307. [PMC free article] [PubMed]
  • Aquadro CF, Lado KM, Noon WA. The rosy region of Drosophila melanogaster and Drosophila simulans. I. Contrasting levels of naturally occurring DNA restriction map variation and divergence. Genetics. 1988 Aug;119(4):875–888. [PMC free article] [PubMed]
  • Barton NH. Linkage and the limits to natural selection. Genetics. 1995 Jun;140(2):821–841. [PMC free article] [PubMed]
  • Begun DJ, Aquadro CF. Levels of naturally occurring DNA polymorphism correlate with recombination rates in D. melanogaster. Nature. 1992 Apr 9;356(6369):519–520. [PubMed]
  • Berget SM, Moore C, Sharp PA. Spliced segments at the 5' terminus of adenovirus 2 late mRNA. Proc Natl Acad Sci U S A. 1977 Aug;74(8):3171–3175. [PMC free article] [PubMed]
  • Berry AJ, Ajioka JW, Kreitman M. Lack of polymorphism on the Drosophila fourth chromosome resulting from selection. Genetics. 1991 Dec;129(4):1111–1117. [PMC free article] [PubMed]
  • Bishop DK, Andersen J, Kolodner RD. Specificity of mismatch repair following transformation of Saccharomyces cerevisiae with heteroduplex plasmid DNA. Proc Natl Acad Sci U S A. 1989 May;86(10):3713–3717. [PMC free article] [PubMed]
  • Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, et al. Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231–238. [PubMed]
  • Carvalho AB, Clark AG. Intron size and natural selection. Nature. 1999 Sep 23;401(6751):344–344. [PubMed]
  • Charlesworth B. The effect of background selection against deleterious mutations on weakly selected, linked variants. Genet Res. 1994 Jun;63(3):213–227. [PubMed]
  • Charlesworth B. The changing sizes of genes. Nature. 1996 Nov 28;384(6607):315–316. [PubMed]
  • Kaplan NL, Hudson RR, Langley CH. The "hitchhiking effect" revisited. Genetics. 1989 Dec;123(4):887–899. [PMC free article] [PubMed]
  • Kersanach R, Brinkmann H, Liaud MF, Zhang DX, Martin W, Cerff R. Five identical intron positions in ancient duplicated genes of eubacterial origin. Nature. 1994 Jan 27;367(6461):387–389. [PubMed]
  • Kirby DA, Muse SV, Stephan W. Maintenance of pre-mRNA secondary structure by epistatic selection. Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9047–9051. [PMC free article] [PubMed]
  • Charlesworth B, Morgan MT, Charlesworth D. The effect of deleterious mutations on neutral molecular variation. Genetics. 1993 Aug;134(4):1289–1303. [PMC free article] [PubMed]
  • Kirkpatrick DT, Petes TD. Repair of DNA loops involves DNA-mismatch and nucleotide-excision repair proteins. Nature. 1997 Jun 26;387(6636):929–931. [PubMed]
  • Kliman RM. Recent selection on synonymous codon usage in Drosophila. J Mol Evol. 1999 Sep;49(3):343–351. [PubMed]
  • Comeron JM. K-Estimator: calculation of the number of nucleotide substitutions per site and the confidence intervals. Bioinformatics. 1999 Sep;15(9):763–764. [PubMed]
  • Kliman RM, Hey J. Reduced natural selection associated with low recombination in Drosophila melanogaster. Mol Biol Evol. 1993 Nov;10(6):1239–1258. [PubMed]
  • Comeron JM, Kreitman M, Aguadé M. Natural selection on synonymous sites is correlated with gene length and recombination in Drosophila. Genetics. 1999 Jan;151(1):239–249. [PMC free article] [PubMed]
  • Kramer B, Kramer W, Williamson MS, Fogel S. Heteroduplex DNA correction in Saccharomyces cerevisiae is mismatch specific and requires functional PMS genes. Mol Cell Biol. 1989 Oct;9(10):4432–4440. [PMC free article] [PubMed]
  • Corrette-Bennett SE, Parker BO, Mohlman NL, Lahue RS. Correction of large mispaired DNA loops by extracts of Saccharomyces cerevisiae. J Biol Chem. 1999 Jun 18;274(25):17605–17611. [PubMed]
  • Kreitman M, Aguadé M. Genetic uniformity in two populations of Drosophila melanogaster as revealed by filter hybridization of four-nucleotide-recognizing restriction enzyme digests. Proc Natl Acad Sci U S A. 1986 May;83(10):3562–3566. [PMC free article] [PubMed]
  • Deloukas P, Schuler GD, Gyapay G, Beasley EM, Soderlund C, Rodriguez-Tomé P, Hui L, Matise TC, McKusick KB, Beckmann JS, et al. A physical map of 30,000 human genes. Science. 1998 Oct 23;282(5389):744–746. [PubMed]
  • de Souza SJ, Long M, Gilbert W. Introns and gene evolution. Genes Cells. 1996 Jun;1(6):493–505. [PubMed]
  • Langley CH, Montgomery E, Hudson R, Kaplan N, Charlesworth B. On the role of unequal exchange in the containment of transposable element copy number. Genet Res. 1988 Dec;52(3):223–235. [PubMed]
  • Detloff P, Sieber J, Petes TD. Repair of specific base pair mismatches formed during meiotic recombination in the yeast Saccharomyces cerevisiae. Mol Cell Biol. 1991 Feb;11(2):737–745. [PMC free article] [PubMed]
  • Leicht BG, Muse SV, Hanczyc M, Clark AG. Constraints on intron evolution in the gene encoding the myosin alkali light chain in Drosophila. Genetics. 1995 Jan;139(1):299–308. [PMC free article] [PubMed]
  • Deutsch M, Long M. Intron-exon structures of eukaryotic model organisms. Nucleic Acids Res. 1999 Aug 1;27(15):3219–3228. [PMC free article] [PubMed]
  • Duret L, Mouchiroud D, Gautier C. Statistical analysis of vertebrate sequences reveals that long genes are scarce in GC-rich isochores. J Mol Evol. 1995 Mar;40(3):308–317. [PubMed]
  • Eanes WF, Kirchner M, Yoon J, Biermann CH, Wang IN, McCartney MA, Verrelli BC. Historical selection, amino acid polymorphism and lineage-specific divergence at the G6pd locus in Drosophila melanogaster and D. simulans. Genetics. 1996 Nov;144(3):1027–1041. [PMC free article] [PubMed]
  • Eyre-Walker A. Recombination and mammalian genome evolution. Proc Biol Sci. 1993 Jun 22;252(1335):237–243. [PubMed]
  • Li WH, Sadler LA. Low nucleotide diversity in man. Genetics. 1991 Oct;129(2):513–523. [PMC free article] [PubMed]
  • Eyre-Walker A. Evidence of selection on silent site base composition in mammals: potential implications for the evolution of isochores and junk DNA. Genetics. 1999 Jun;152(2):675–683. [PMC free article] [PubMed]
  • Llopart A, Aguadé M. Nucleotide polymorphism at the RpII215 gene in Drosophila subobscura. Weak selection on synonymous mutations. Genetics. 2000 Jul;155(3):1245–1252. [PMC free article] [PubMed]
  • Felsenstein J. The evolutionary advantage of recombination. Genetics. 1974 Oct;78(2):737–756. [PMC free article] [PubMed]
  • Ludwig MZ, Kreitman M. Evolutionary dynamics of the enhancer region of even-skipped in Drosophila. Mol Biol Evol. 1995 Nov;12(6):1002–1011. [PubMed]
  • Graur D, Shuali Y, Li WH. Deletions in processed pseudogenes accumulate faster in rodents than in humans. J Mol Evol. 1989 Apr;28(4):279–285. [PubMed]
  • Marchionni M, Gilbert W. The triosephosphate isomerase gene from maize: introns antedate the plant-animal divergence. Cell. 1986 Jul 4;46(1):133–141. [PubMed]
  • Hey J. Selfish genes, pleiotropy and the origin of recombination. Genetics. 1998 Aug;149(4):2089–2097. [PMC free article] [PubMed]
  • Smith JM, Haigh J. The hitch-hiking effect of a favourable gene. Genet Res. 1974 Feb;23(1):23–35. [PubMed]
  • Hill WG, Robertson A. The effect of linkage on limits to artificial selection. Genet Res. 1966 Dec;8(3):269–294. [PubMed]
  • Moriyama EN, Hartl DL. Codon usage bias and base composition of nuclear genes in Drosophila. Genetics. 1993 Jul;134(3):847–858. [PMC free article] [PubMed]
  • Hudson RR. How can the low levels of DNA sequence variation in regions of the drosophila genome with low recombination rates be explained? Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):6815–6818. [PMC free article] [PubMed]
  • Moriyama EN, Powell JR. Intraspecific nuclear DNA variation in Drosophila. Mol Biol Evol. 1996 Jan;13(1):261–277. [PubMed]
  • Moriyama EN, Petrov DA, Hartl DL. Genome size and intron size in Drosophila. Mol Biol Evol. 1998 Jun;15(6):770–773. [PubMed]
  • Mouchiroud D, Gautier C, Bernardi G. Frequencies of synonymous substitutions in mammals are gene-specific and correlated with frequencies of nonsynonymous substitutions. J Mol Evol. 1995 Jan;40(1):107–113. [PubMed]
  • Hughes AL, Yeager M. Comparative evolutionary rates of introns and exons in murine rodents. J Mol Evol. 1997 Aug;45(2):125–130. [PubMed]
  • Mount SM, Burks C, Hertz G, Stormo GD, White O, Fields C. Splicing signals in Drosophila: intron size, information content, and consensus sequences. Nucleic Acids Res. 1992 Aug 25;20(16):4255–4262. [PMC free article] [PubMed]
  • Izban MG, Luse DS. Factor-stimulated RNA polymerase II transcribes at physiological elongation rates on naked DNA but very poorly on chromatin templates. J Biol Chem. 1992 Jul 5;267(19):13647–13655. [PubMed]
  • Nag DK, White MA, Petes TD. Palindromic sequences in heteroduplex DNA inhibit mismatch repair in yeast. Nature. 1989 Jul 27;340(6231):318–320. [PubMed]
  • Ogata H, Fujibuchi W, Kanehisa M. The size differences among mammalian introns are due to the accumulation of small deletions. FEBS Lett. 1996 Jul 15;390(1):99–103. [PubMed]
  • Stephan W, Kirby DA. RNA folding in Drosophila shows a distance effect for compensatory fitness interactions. Genetics. 1993 Sep;135(1):97–103. [PMC free article] [PubMed]
  • Ohta T. Synonymous and nonsynonymous substitutions in mammalian genes and the nearly neutral theory. J Mol Evol. 1995 Jan;40(1):56–63. [PubMed]
  • Ophir R, Graur D. Patterns and rates of indel evolution in processed pseudogenes from humans and murids. Gene. 1997 Dec 31;205(1-2):191–202. [PubMed]
  • Stephan W, Rodriguez VS, Zhou B, Parsch J. Molecular evolution of the metallothionein gene Mtn in the melanogaster species group: results from Drosophila ananassae. Genetics. 1994 Sep;138(1):135–143. [PMC free article] [PubMed]
  • Otto SP, Barton NH. The evolution of recombination: removing the limits to natural selection. Genetics. 1997 Oct;147(2):879–906. [PMC free article] [PubMed]
  • Tachida H. Molecular evolution in a multisite nearly neutral mutation model. J Mol Evol. 2000 Jan;50(1):69–81. [PubMed]
  • Petrov DA, Hartl DL. High rate of DNA loss in the Drosophila melanogaster and Drosophila virilis species groups. Mol Biol Evol. 1998 Mar;15(3):293–302. [PubMed]
  • Tajima F. Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics. 1989 Nov;123(3):585–595. [PMC free article] [PubMed]
  • Takano TS. Rate variation of DNA sequence evolution in the Drosophila lineages. Genetics. 1998 Jun;149(2):959–970. [PMC free article] [PubMed]
  • Tatusova TA, Madden TL. BLAST 2 Sequences, a new tool for comparing protein and nucleotide sequences. FEMS Microbiol Lett. 1999 May 15;174(2):247–250. [PubMed]
  • Petrov DA, Lozovskaya ER, Hartl DL. High intrinsic rate of DNA loss in Drosophila. Nature. 1996 Nov 28;384(6607):346–349. [PubMed]
  • Thompson JD, Gibson TJ, Plewniak F, Jeanmougin F, Higgins DG. The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res. 1997 Dec 15;25(24):4876–4882. [PMC free article] [PubMed]
  • Saitou N, Ueda S. Evolutionary rates of insertion and deletion in noncoding nucleotide sequences of primates. Mol Biol Evol. 1994 May;11(3):504–512. [PubMed]
  • True JR, Mercer JM, Laurie CC. Differences in crossover frequency and distribution among three sibling species of Drosophila. Genetics. 1996 Feb;142(2):507–523. [PMC free article] [PubMed]
  • Sambrook J. Adenovirus amazes at Cold Spring Harbor. Nature. 1977 Jul 14;268(5616):101–104. [PubMed]
  • Tsurushita N, Korn LJ. Effects of intron length on differential processing of mouse mu heavy-chain mRNA. Mol Cell Biol. 1987 Jul;7(7):2602–2605. [PMC free article] [PubMed]
  • Upholt WB, Sandell LJ. Exon/intron organization of the chicken type II procollagen gene: intron size distribution suggests a minimal intron size. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2325–2329. [PMC free article] [PubMed]
  • Schmid KJ, Nigro L, Aquadro CF, Tautz D. Large number of replacement polymorphisms in rapidly evolving genes of Drosophila. Implications for genome-wide surveys of DNA polymorphism. Genetics. 1999 Dec;153(4):1717–1729. [PMC free article] [PubMed]
  • Vincent A, Petes TD. Mitotic and meiotic gene conversion of Ty elements and other insertions in Saccharomyces cerevisiae. Genetics. 1989 Aug;122(4):759–772. [PMC free article] [PubMed]
  • Shah DM, Hightower RC, Meagher RB. Genes encoding actin in higher plants: intron positions are highly conserved but the coding sequences are not. J Mol Appl Genet. 1983;2(1):111–126. [PubMed]
  • Vinogradov AE. Intron-genome size relationship on a large evolutionary scale. J Mol Evol. 1999 Sep;49(3):376–384. [PubMed]
  • Zeng LW, Comeron JM, Chen B, Kreitman M. The molecular clock revisited: the rate of synonymous vs. replacement change in Drosophila. Genetica. 1998;102-103(1-6):369–382. [PubMed]
  • Shields DC, Sharp PM, Higgins DG, Wright F. "Silent" sites in Drosophila genes are not neutral: evidence of selection among synonymous codons. Mol Biol Evol. 1988 Nov;5(6):704–716. [PubMed]

Articles from Genetics are provided here courtesy of Genetics Society of America

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...