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. 1997 Mar;145(3):759–769. doi: 10.1093/genetics/145.3.759

Structural and Functional Differences in the Promoter and 5' Flanking Region of Ldh-B within and between Populations of the Teleost Fundulus Heteroclitus

P M Schulte 1, M Gomez-Chiarri 1, D A Powers 1
PMCID: PMC1207860  PMID: 9055085

Abstract

We have investigated the mechanisms underlying differences in the transcriptional regulation of lactate dehydrogenase-B (Ldh-B) between northern and southern populations of a teleost fish, Fundulus heteroclitus. A 1-kb region immediately 5' of the gene was sequenced from populations throughout the species range. There were two major allele classes in the sample, one containing alleles from Maine and another containing those from Florida. Populations from intermediate localities contained both allele classes. Some individuals from Georgia had sequences intermediate between the two classes, representing either ancestral alleles or recombinants. Tests of neutrality were applied to determine whether observed variation was consistent with neutral expectations. Significant deviations from neutral expectations were detected for the 5' flanking region, but not for other loci. The functional consequences of flanking sequence variation were assessed by transfection of reporter gene constructs into cultured cells and injection into living fish. Consistent with observed variation in Ldh-B transcription rate between populations, significant differences in reporter gene activity were driven by flanking regions from northern and southern populations both in cell culture and in vivo. This functional differentiation, coupled with departures from neutral expectations, suggests that selection may have acted on the regulation of Ldh-B in F. heteroclitus.

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Selected References

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  1. Ballard J. W., Kreitman M. Unraveling selection in the mitochondrial genome of Drosophila. Genetics. 1994 Nov;138(3):757–772. doi: 10.1093/genetics/138.3.757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Begun D. J., Aquadro C. F. Molecular population genetics of the distal portion of the X chromosome in Drosophila: evidence for genetic hitchhiking of the yellow-achaete region. Genetics. 1991 Dec;129(4):1147–1158. doi: 10.1093/genetics/129.4.1147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bernardi G., Sordino P., Powers D. A. Concordant mitochondrial and nuclear DNA phylogenies for populations of the teleost fish Fundulus heteroclitus. Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9271–9274. doi: 10.1073/pnas.90.20.9271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Berry A. J., Ajioka J. W., Kreitman M. Lack of polymorphism on the Drosophila fourth chromosome resulting from selection. Genetics. 1991 Dec;129(4):1111–1117. doi: 10.1093/genetics/129.4.1111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cashon R. E., Van Beneden R. J., Powers D. A. Biochemical genetics of Fundulus heteroclitus (L.). IV. Spatial variation in gene frequencies of Idh-A, Idh-B, 6-Pgdh-A, and Est-S. Biochem Genet. 1981 Aug;19(7-8):715–728. doi: 10.1007/BF00484004. [DOI] [PubMed] [Google Scholar]
  6. Charlesworth B., Morgan M. T., Charlesworth D. The effect of deleterious mutations on neutral molecular variation. Genetics. 1993 Aug;134(4):1289–1303. doi: 10.1093/genetics/134.4.1289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Crawford D. L., Powers D. A. Molecular basis of evolutionary adaptation at the lactate dehydrogenase-B locus in the fish Fundulus heteroclitus. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9365–9369. doi: 10.1073/pnas.86.23.9365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. DiMichele L., Paynter K. T., Powers D. A. Evidence of lactate dehydrogenase-B allozyme effects in the teleost, Fundulus heteroclitus. Science. 1991 Aug 23;253(5022):898–900. doi: 10.1126/science.1876847. [DOI] [PubMed] [Google Scholar]
  9. DiMichele L., Powers D. A. LDH-B genotype-specific hatching times of Fundulus heteroclitus embryos. Nature. 1982 Apr 8;296(5857):563–564. doi: 10.1038/296563a0. [DOI] [PubMed] [Google Scholar]
  10. DiMichele L., Powers D. A. Physiological basis for swimming endurance differences between LDH-B genotypes of Fundulus heteroclitus. Science. 1982 May 28;216(4549):1014–1016. doi: 10.1126/science.7079747. [DOI] [PubMed] [Google Scholar]
  11. Dynan W. S., Tjian R. The promoter-specific transcription factor Sp1 binds to upstream sequences in the SV40 early promoter. Cell. 1983 Nov;35(1):79–87. doi: 10.1016/0092-8674(83)90210-6. [DOI] [PubMed] [Google Scholar]
  12. Fu Y. X., Li W. H. Statistical tests of neutrality of mutations. Genetics. 1993 Mar;133(3):693–709. doi: 10.1093/genetics/133.3.693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Holstege F. C., van der Vliet P. C., Timmers H. T. Instability of human TATA-binding protein CAG triplet repeats during amplification by PCR. Biochim Biophys Acta. 1994 Sep 13;1219(1):157–159. doi: 10.1016/0167-4781(94)90260-7. [DOI] [PubMed] [Google Scholar]
  14. Hudson R. R. Estimating the recombination parameter of a finite population model without selection. Genet Res. 1987 Dec;50(3):245–250. doi: 10.1017/s0016672300023776. [DOI] [PubMed] [Google Scholar]
  15. Hudson R. R., Kaplan N. L. The coalescent process in models with selection and recombination. Genetics. 1988 Nov;120(3):831–840. doi: 10.1093/genetics/120.3.831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hudson R. R., Kreitman M., Aguadé M. A test of neutral molecular evolution based on nucleotide data. Genetics. 1987 May;116(1):153–159. doi: 10.1093/genetics/116.1.153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kreitman M., Hudson R. R. Inferring the evolutionary histories of the Adh and Adh-dup loci in Drosophila melanogaster from patterns of polymorphism and divergence. Genetics. 1991 Mar;127(3):565–582. doi: 10.1093/genetics/127.3.565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Langer S. J., Ostrowski M. C. Negative regulation of transcription in vitro by a glucocorticoid response element is mediated by a trans-acting factor. Mol Cell Biol. 1988 Sep;8(9):3872–3881. doi: 10.1128/mcb.8.9.3872. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Leach G. J., Taylor M. H. Seasonal measurements of serum glucose and serum cortisol in a natural population of Fundulus heteroclitus L. Comp Biochem Physiol A Comp Physiol. 1977;56(2):217–223. doi: 10.1016/0300-9629(77)90188-8. [DOI] [PubMed] [Google Scholar]
  20. Odgers W. A., Healy M. J., Oakeshott J. G. Nucleotide polymorphism in the 5' promoter region of esterase 6 in Drosophila melanogaster and its relationship to enzyme activity variation. Genetics. 1995 Sep;141(1):215–222. doi: 10.1093/genetics/141.1.215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Roeder R. G. The complexities of eukaryotic transcription initiation: regulation of preinitiation complex assembly. Trends Biochem Sci. 1991 Nov;16(11):402–408. doi: 10.1016/0968-0004(91)90164-q. [DOI] [PubMed] [Google Scholar]
  22. Segal J. A., Crawford D. L. LDH-B enzyme expression: the mechanisms of altered gene expression in acclimation and evolutionary adaptation. Am J Physiol. 1994 Oct;267(4 Pt 2):R1150–R1153. doi: 10.1152/ajpregu.1994.267.4.R1150. [DOI] [PubMed] [Google Scholar]
  23. Simonsen K. L., Churchill G. A., Aquadro C. F. Properties of statistical tests of neutrality for DNA polymorphism data. Genetics. 1995 Sep;141(1):413–429. doi: 10.1093/genetics/141.1.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Tajima F. Evolutionary relationship of DNA sequences in finite populations. Genetics. 1983 Oct;105(2):437–460. doi: 10.1093/genetics/105.2.437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Tajima F. Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics. 1989 Nov;123(3):585–595. doi: 10.1093/genetics/123.3.585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Takeno T., Li S. S. Structure of the human lactate dehydrogenase B gene. Biochem J. 1989 Feb 1;257(3):921–924. doi: 10.1042/bj2570921. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Wolff J. A., Malone R. W., Williams P., Chong W., Acsadi G., Jani A., Felgner P. L. Direct gene transfer into mouse muscle in vivo. Science. 1990 Mar 23;247(4949 Pt 1):1465–1468. doi: 10.1126/science.1690918. [DOI] [PubMed] [Google Scholar]
  28. von Harsdorf R., Schott R. J., Shen Y. T., Vatner S. F., Mahdavi V., Nadal-Ginard B. Gene injection into canine myocardium as a useful model for studying gene expression in the heart of large mammals. Circ Res. 1993 Mar;72(3):688–695. doi: 10.1161/01.res.72.3.688. [DOI] [PubMed] [Google Scholar]

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