Evidence that strong positive selection drives neofunctionalization in the tandemly duplicated polyhomeotic genes in Drosophila
Edited by Tomoko Ohta, National Institute of Genetics, Mishima, Japan, and approved February 6, 2008
Abstract
The polyhomeotic (ph) locus in Drosophila melanogaster consists of the two tandemly duplicated genes ph-d (distal) and ph-p (proximal). They code for transcriptional repressors belonging to the Polycomb group proteins, which regulate homeotic genes and hundreds of other loci. Although the duplication of ph occurred at least 25 million to 30 million years ago, both copies are very similar to each other at both the DNA and the protein levels, probably because of the action of frequent gene conversion. Despite this homogenizing force, differential regulation of both transcriptional units suggests that the functions of the duplicates have begun to diverge. Here, we provide evidence that this functional divergence is driven by positive selection. Based on resequencing of an ≈30-kb region around the ph locus in an African sample of D. melanogaster X chromosomes, we identified a selective sweep, estimated its age and the strength of selection, and mapped the target of selection to a narrow interval of the ph-p gene. This noncoding region contains a large intron with several regulatory elements that are absent in the ph-d duplicate. Our results suggest that neofunctionalization has been achieved in the Drosophila ph genes through the action of strong positive selection and the inactivation of gene conversion in part of the gene.
Data Availability
Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. AM943662–AM943805).
Acknowledgments.
We thank Anne Wilken and Simone Lange for excellent technical assistance; David De Lorenzo, Hideki Innan, Pleuni Pennings, and Molly Przeworski for valuable suggestions; Tim Sackton for help with the Drosophila assemblies; and Neel Randsholt for introducing us to polyhomeotic. This work was supported by the Deutsche Forschungsgemeinschaft Grant STE 325/7.
References
1
S Ohno Evolution by Gene Duplication (Springer, Berlin, 1970).
2
T Ohta Evolution and Variation of Multigene Families: Lecture Notes in Biomathematics 37 (Springer, Berlin, 1980).
3
AG Clark, Invasion and maintenance of a gene duplication. Proc Natl Acad Sci USA 91, 2950–2954 (1994).
4
M Lynch, A Force, The probability of duplicate gene preservation by subfunctionalization. Genetics 154, 459–473 (2000).
5
JB Walsh, Population-genetic models of the fates of duplicate genes. Genetica 118, 279–294 (2003).
6
JB Walsh, How often do duplicated genes evolve new functions. Genetics 139, 421–428 (1995).
7
H Innan, A two-locus gene conversion model with selection and its application to the human RHCE and RHD genes. Proc Natl Acad Sci USA 100, 8793–8798 (2003).
8
J Maynard Smith, J Haigh, The hitch-hiking effect of a favourable gene. Genet Res 23, 23–35 (1974).
9
H Innan, Y Kim, Pattern of polymorphism after strong artificial selection in a domestication event. Proc Natl Acad Sci USA 101, 10667–10672 (2004).
10
Y Kim, W Stephan, Detecting a local signature of genetic hitchhiking along a recombining chromosome. Genetics 160, 765–777 (2002).
11
M Przeworski, Estimating the time since the fixation of a beneficial allele. Genetics 164, 1667–1676 (2003).
12
R Nielsen, et al., Genomic scans for selective sweeps using SNP data. Genome Res 15, 1566–1575 (2005).
13
H Li, W Stephan, Inferring the demographic history and rate of adaptive substitution in Drosophila. PLoS Genet 13, e166 (2006).
14
DI Nurminsky, D De Aguiar, CD Bustamante, DL Hartl, Chromosomal effects of rapid gene evolution in Drosophila melanogaster. Science 291, 128–130 (2001).
15
TA Schlenke, DJ Begun, Strong selective sweep associated with a transposon insertion in Drosophila simulans. Proc Natl Acad Sci USA 101, 1626–1631 (2004).
16
DJ Orengo, M Aguadé, Genome scans of variation and adaptive change: Extended analysis of a candidate locus close to the phantom gene region in Drosophila melanogaster. Mol Biol Evol 24, 1122–1129 (2007).
17
S Beisswanger, W Stephan, D De Lorenzo, Evidence for a selective sweep in the wapl region of Drosophila melanogaster. Genetics 172, 265–274 (2006).
18
YB Schwartz, V Pirrotta, Polycomb silencing mechanisms and the management of genomic programs. Nat Rev Gen 8, 9–22 (2007).
19
J Deatrick, M Daly, NB Randsholt, HW Brock, The complex genetic locus polyhomeotic in Drosophila melanogaster potentially encodes two homologous zinc-finger proteins. Gene 105, 185–195 (1991).
20
JW Hodgson, et al., The polyhomeotic locus of Drosophila melanogaster is transcriptionally and posttranscriptionally regulated during embryogenesis. Mech Dev 66, 69–81 (1997).
21
G Grumbling, V Strelets, FlyBase: Anatomical data, images and queries. Nucleic Acids Res 34, D484–D488 (2006).
22
J-M Dura, et al., A complex genetic locus, polyhomeotic, is required for segmental specification and epidermal development in D. melanogaster. Cell 51, 829–839 (1987).
23
L Ometto, S Glinka, D De Lorenzo, W Stephan, Inferring the impact of demography and selection on Drosophila melanogaster from a chromosome-wide DNA polymorphism study. Mol Biol Evol 22, 2119–2130 (2005).
24
JK Kelly, A test of neutrality based on interlocus associations. Genetics 146, 1197–1206 (1997).
25
WG Hill, A Robertson, Linkage disequilibrium in finite populations. Theor Appl Genet 38, 226–231 (1968).
26
W Stephan, YS Song, CH Langley, The hitchhiking effect on linkage disequilibrium between linked neutral loci. Genetics 172, 2647–2663 (2006).
27
F Tajima, Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics 123, 585–595 (1989).
28
Y-X Fu, W-H Li, Statistical tests of neutrality of mutations. Genetics 133, 693–709 (1993).
29
RR Hudson, M Kreitman, M Aguadé, A test of neutral molecular evolution based on nucleotide data. Genetics 116, 153–159 (1987).
30
H Innan, The coalescent and infinite-site model of a small multigene family. Genetics 163, 803–810 (2003).
31
JD Jensen, et al., Distinguishing between selective sweeps and demography using DNA polymorphism data. Genetics 170, 1401–1410 (2005).
32
M Slatkin, RR Hudson, Pairwise comparisons of mitochondrial DNA sequences in stable and exponentially growing populations. Genetics 129, 555–562 (1991).
33
FJ Ayala, ES Balakirev, AG Saez, Genetic polymorphism at two linked loci, Sod and Est-6, in Drosophila melanogaster. Gene 300, 19–29 (2002).
34
S Glinka, L Ometto, S Mousset, W Stephan, D De Lorenzo, Demography and natural selection have shaped genetic variation in Drosophila melanogaster: A multilocus approach. Genetics 165, 1269–1278 (2003).
35
W Stephan, H Li, The recent demographic and adaptive history of Drosophila melanogaster. Heredity 98, 65–68 (2007).
36
J Majewski, J Ott, Distribution and characterization of regulatory elements in the human genome. Genome Res 12, 1827–1836 (2002).
37
PR Haddrill, B Charlesworth, DL Halligan, P Andolfatto, Patterns of intron evolution in Drosophila are dependent upon length and GC content. Genome Biol 6, R67 (2005).
38
DL Halligan, PD Keightley, Ubiquitous selective constraints in the Drosophila genome revealed by a genome-wide interspecies comparison. Genome Res 16, 875–884 (2006).
39
S Casillas, A Barbadilla, CM Bergman, Purifying selection maintains highly conserved noncoding sequences in Drosophila. Mol Biol Evol 24, 2222–2234 (2007).
40
, Evolution of genes and genomes on the Drosophila phylogeny. Nature 450, 203–218 (2007).
41
CAM Russo, N Takezsaki, M Nei, Molecular phylogeny and divergence times of Drosophilid species. Mol Biol Evol 12, 391–404 (1995).
42
H Innan, A method for estimating the mutation, gene conversion, and recombination parameters in small multigene families. Genetics 161, 865–872 (2002).
43
KM Teshima, H Innan, Neofunctionalization of duplicated genes under the pressure of gene conversion. Genetics, 2008).
44
DJ Begun, CF Aquadro, African and North American populations of Drosophila melanogaster are very different at the DNA level. Nature 365, 548–550 (1993).
45
J Rozas, JC Sánchez-Del Barrio, X Messeguer, R Rozas, DnaSP, DNA polymorphism analyses by the coalescent and other methods. Bioinformatics 19, 2496–2497 (2003).
46
GA Watterson, On the number of segregating sites in genetical models without recombination. Theor Pop Biol 7, 256–276 (1975).
47
F Tajima, Evolutionary relationship of DNA sequences in finite populations. Genetics 105, 437–460 (1983).
48
M Nei Molecular Evolutionary Genetics (Columbia Univ Press, New York), pp. 177–178 (1987).
49
G McVean, P Awadalla, P Fearnhead, A coalescent-based method for detecting and estimating recombination rates from gene sequences. Genetics 160, 1231–1241 (2002).
50
K Cartharius, et al., MatInspector and beyond: Promoter analysis based on transcription factor binding sites. Bioinformatics 21, 2933–2942 (2005).
51
Y-J Li, Y Satta, N Takahata, Paleo-demography of the Drosophila melanogaster subgroup: Application of the maximum-likelihood method. Genes Genet Syst 74, 117–127 (1999).
Information & Authors
Information
Published in
Cover image: Nanobacteria-like particles from human blood. Structures resembling nanoscale bacteria, possessing peculiar characteristics, have been proposed as the cause of a number of diseases. But new results show that inert nanostructures formed of amorphous calcium carbonate meet existing criteria for identification as living nanobacteria. See the article by Martel and Young on pages 5549–5554. Image courtesy of Jan Martel and John Ding-E Young.
Classifications
Copyright
© 2008 by The National Academy of Sciences of the USA.
Data Availability
Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. AM943662–AM943805).
Submission history
Received: November 16, 2007
Published online: April 8, 2008
Published in issue: April 8, 2008
Keywords
Acknowledgments
We thank Anne Wilken and Simone Lange for excellent technical assistance; David De Lorenzo, Hideki Innan, Pleuni Pennings, and Molly Przeworski for valuable suggestions; Tim Sackton for help with the Drosophila assemblies; and Neel Randsholt for introducing us to polyhomeotic. This work was supported by the Deutsche Forschungsgemeinschaft Grant STE 325/7.
Notes
This article is a PNAS Direct Submission.
Authors
Competing Interests
The authors declare no conflict of interest.
Metrics & Citations
Metrics
Citation statements
Altmetrics
Citations
Cite this article
105 (14) 5447-5452,
Export the article citation data by selecting a format from the list below and clicking Export.
Cited by
Loading...
View Options
View options
PDF format
Download this article as a PDF file
DOWNLOAD PDFLogin options
Check if you have access through your login credentials or your institution to get full access on this article.
Personal login Institutional LoginRecommend to a librarian
Recommend PNAS to a LibrarianPurchase options
Purchase this article to access the full text.