Neutrality
Tests of DNA Sequences
Experimental evolution in the lab
Mitochondrial genetics of aging in Drosophila
How do mtDNA haplotypes affect fitness?
Ecological genetics of barnacles
Neutrality
Tests of DNA Sequences 
(click icon to download Microsoft® Powerpoint®
slide)
 We
are generally interested in using DNA sequence surveys of polymorphism
and divergence to study how mutation, selection and drift act on
specific genes. Most of our work has focused on mtDNA where an excess
of amino acid polymorphism indicates that deleterious mutations
govern mtDNA evolution. Our recent studies have focused on regions
of very low recombination at the tip of the X and 4th chromosome
in Drosophila. These data show an “mtDNA-like” pattern
of excess amino acid polymorphism at the tip of the X, and show
how recombination and dominance modulate selection on amino acid
variation.
Relevant publications
| Rand, D. M., M. L. Dorfsman and L. M. Kann
1994 Neutral and non-neutral evolution of Drosophila mitochondrial
DNA. Genetics 138: 741-756. |
| Rand, D. M., 1996 Neutrality tests of molecular
markers and the connection between DNA polymorphism, demography,
and conservation biology. Conservation Biology 10: 665-671. |
| Rand, D. M. and L. M. Kann, 1996 Excess amino
acid polymorphism in mitochondrial DNA: contrasts among genes
from Drosophila, mice, and humans. Molecular Biology and Evolution
13(6):735-748. |
| Rand, D. M. and L. M. Kann. 1998. Mutation
and selection at silent and replacement sites in the evolution
of animal mitochondrial DNA. Genetica 102/103: 393-407. |
| Rand, D. M., D. M. Weinreich, and B. O Cezairliyan.
2000. Neutrality tests of conservative and radical amino acid
changes in nuclear- and mitochondrially-encoded proteins.
Gene 291:115-125. |
| Weinreich, D. M. and D. M. Rand, 2000 Contrasting
patterns of non-neutral evolution in proteins encoded in nuclear
and mitochondrial genomes. Genetics 2000 156: 385-399. |
| Rand, D. M. 2001. Mitochondrial genomics flies
high. Trends in Ecology and Evolution 16:2-4. |
| Rand, D. M. 2001. The units of selection on
mitochondrial DNA. Annual Review of Ecology and Systematics
32: 415-448. |
| Sheldahl LA, Weinreich DM, Rand DM. Recombination,
dominance and selection on amino acid polymorphism in the
Drosophila genome: contrasting patterns on the X and fourth
chromosomes. Genetics. 2003 Nov;165(3):1195-208. [PDF
reprint] |
| Kingan SB, Tatar M, Rand DM. Reduced polymorphism
in the chimpanzee semen coagulating protein, semenogelin I.
J Mol Evol. 2003 Aug;57(2):159-69. [PDF
reprint] |
| Rand, D. M., R. A. Haney, A. J. Fry. 2004.
Cytonuclear coevolution: the genomics of cooperation. Trends
in Ecology and Evolution, 19(12):645-653. [PDF
reprint] |
| Ballard. J. W. O. and D. M. Rand. 2005. The population
biology mitochondrial DNA and its phylogenetic implications. Annual Review
of Ecology, Evolution and Systematics 36:621-642. |
| NOTE: See also the ScienceNOW
web story on this paper. |
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Experimental evolution
in the lab
 We
use Drosophila population cage experiments to study selection on
genes and genomes. We have done several cage experiments focusing
on mtDNA, and these have shown that selection on mtDNA depends on
the nuclear genetic background of the strains studied. We have dissected
these mito-nuclear interactions using chromosome-specific studies
in D. melanogaster. These have indicated that X-chromosome / cytoplasm
fitness interactions are very different from autosome / cytoplasm
interactions, and further show sexually antagonistic fitness interactions.
More recently we have used laboratory natural selection
in Drosophila melanogaster to discover chromosomal factors that
respond to temperature selection. Using microsatellite markers we
have mapped QTL for temperature-specific fitness near the tip of
the X chromosome. We are pursuing the fine scale mapping of this
regions, and microarray analysis of these evolved populations
Relevant publications
| Hutter, C. M. and D. M. Rand, 1995 Competition
between mitochondrial haplotypes in distinct nuclear genetic
environments: Drosophila pseudoobscura versus D. persimilis.
Genetics 140: 537-548. |
| Kilpatrick, S. R. and D. M. Rand, 1995 Conditional
hitchhiking of mitochondrial DNA: frequency shifts of Drosophila
melanogaster mtDNA variants depend on nuclear genetic background.
Genetics 141:1113-1124. |
| Datta, S., M. Kiparsky, D. M. Rand, and J.
Arnold. 1996. A statistical test of a neutral model using
the dynamics of cytonuclear disequilibria. Genetics 144:1985-1992. |
| Rand, D. M., A. G. Clark, and L. M. Kann 2001.
Sexually antagonistic cytonuclear fitness interactions in
Drosophila melanogaster. Genetics 2001 159: 173-187. |
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Mitochondrial
genetics of aging in Drosophila
The mitochondrial free radical theory of aging posiits that physiological
decline is due to accumulated effects of free radical damage stemming
from mitochondrial respiration. We are testing this hypothesis using
Drosophila carrying different mtDNA haplotyes. Our data
so far show a correlation between the degree of divergence between
mtDNNAs and the amount of effect they have on altering longevity.
Relevant publications
| Kann, L. M., E. R. Rosenblum, and D. M. Rand.
1998. Aging, mating, and the evolution of heteroplasmy for
mtDNA length variants in Drosophila melanogaster. Proc. Natl.
Acad. Sci. 95:2372-2377. |
| Fry, A. and Rand D.M. 2002. Wolbachia interactions
that determine Drosophila melanogaster survival. Evolution
56(10):1976-81. |
| Tatar, M. and D. M. Rand. 2002. Aging: Dietary
advice on Q. Science 295:54-55. |
| Rand, D.M. 2005. Mitochondrial genetics of
aging: problems in inter-genomic conflict resolutions. Science
Sci. Aging Knowl. Environ., Vol. 2005, Issue 45, pp. re5,
9 November 2005[DOI:10.1126/sageke.2005.45.re5]. |
Rand, D. M., A. J. Fry, and L. A. Sheldahl.
2006. Nuclear-mitochondrial epistasis and Drosophila
aging: Introgression of D. simulans mtDNA alters
longevity in D. melanogaster nuclear backgrounds.
Genetics 172: January in press (e-pub ahead of
print. doi:10.1534/genetics.105.046698) |
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How do mtDNA haplotypes
affect fitness?
 We
have used a number of different fitness assays to determine the
funtional significance of mtDNA In natural populations. Typical
experiments involve population cage experiments, and these have
shown that the fitness of mtDNA haplotyes varies in different nuclear
genetic backgrounds. More recently we Have explored X-chromosome
x mtDNA interactions and shown that these chromosomes have unique
Sex-specific fitness dynamics. We are attempting to dissect the
genetic architecture of nuclear-mtDNA Interactions through enzyme
assays of mitochondrial enzyme complexes, and comparative sequence
Analysis.
Relevant publications
| Fry, A.F., M. R. Palmer, and D. M. Rand. 2004.
Variable fitness effects of Wolbachia infection in Drosophila
melanogaster. Heredity 93(4):379-389. [PDF
reprint] |
| Rand, D. M. 2001. The units of selection on
mitochondrial DNA. Annual Review of Ecology and Systematics
32: 415-448. |
Rand, D. M., A. G. Clark, and L. M. Kann 2001.
Sexually antagonistic cytonuclear fitness interactions in
Drosophila melanogaster. Genetics 2001 159:
173-187. |
| Sackton TB, Haney RA, Rand DM. Cytonuclear
coadaptation in Drosophila: disruption of cytochrome
c oxidase activity in backcross genotypes. Evolution . 2003
Oct;57(10):2315-25. [PDF reprint] |
| Townsend JP, Rand DM. Mitochondrial genome
size variation in New World and Old World populations of Drosophila
melanogaster. Heredity. 2004 Jul;93(1):98-103. [PDF
reprint] |
| (and see Experimental Evolution, above) |
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Ecological genetics of
barnacles
Barnacles that settle at different tidal heights
and with different exposure to the sun can experience extremely
different physical environments. We are interested in how these
abiotic factors, in association with patterns of larval supply,
can influence genetic variation in barnacles. Notably, the mannose
phosphate isomerase locus (Mpi) shows repeatable zonation in genotype
frequencies between high and low tidal levels in thermally stressed
habitats. In these same samples, neutral markers show no zonation,
suggesting that selection is acting at or near the Mpi locus.
We have extended these studies on a biogeographic scale and found
that the Mpi and Gpi allozyme loci show significant differences
in tidal-height zonation between Maine and Rhode Island. We are
testing the hypothesis that differences in plankton composition,
and hence carbohydrate supply, are the basis for neutral vs. non-neutral
variation at these two loci. Future studies will involve extensive
nucleotide sequence surveys of the Mpi and Gpi loci, analyses
of enzyme activities of the allozyme alleles, and field experiments
examining the functional significance of specific nucleotide variants.
Relevant publications
| Schmidt, P. S. and D. M. Rand. 1999. Intertidal
microhabitat and selection at MPI: Interlocus contrasts
in the northern acorn barnacle. Evolution 53:135-146. |
Schmidt, P. S. M. D. Bertness, and D. M Rand 2000. Environmental
heterogeneity and balancing selection in the northern acorn
barnacle. Proc. Roy. Soc. London, B 267:379-384. |
| Brown, A. F. L. M. Kann and D. M. Rand, 2001.
Gene flow versus local adaptation in the northern acorn
barnacle, Semibalanus balanoides: insights from mtDNA control
region polymorphisms. Evolution 55: 1972–1979. |
| Schmidt, P. S., and D. M. Rand. 2001 Adaptive
maintenance of genetic polymorphism in an intertidal barnacle:
Habitat and life history stage-specific survivorship of
Mpi genotypes. Evolution 55(7):1336-44. |
| Rand, D. M., Spaeth, P. S., Sackton, T, Schmidt,
P. S. 2002. Ecological genetics of the Mpi and Gpi polymorphisms
in the northern acorn barnacle and the spatial scale of
neutral and non-neutral variation. Integrative and Comparative
Biology 42:825-836. |
We gratefully acknowledge research
support from the
Population Biology Panel at the National
Science Foundation, and the National
Institute of Aging.
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