Anthony D LongAssociate Professor, Ecology & Evolutionary Biology |
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Research Interests |
quantitative and population genetics | |
| URL | My Home Page | |
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Research Abstract |
What is the Nature of Quantitative Variation? The inheritance of many traits of evolutionary, medical, and agricultural importance is polygenic in nature. The observation that quantitative traits have ample standing genetic variation, despite apparent stabilizing selection which should erode this variation over time, is a paradox in evolutionary biology. A number of theoretical models address the question what maintains quantitative genetic variation, yet all models rely on assumptions regarding underlying genetic parameters. This is problematic, as despite great recent advances in our understanding of 'Mendelian' traits, we still know little about the molecular genetic basis of quantitative traits. My research uses the powerful genetic and molecular tools of Drosophila melanogaster to elucidate the molecular genetic basis of polygenic characters. The information obtained from this model system can be used to address the basis of polygenic variation in other organisms. Some of the questions I am currently attempting to answer are: What is the distribution of allelic effects for quantitative traits? Early studies focused on mapping the locations and estimating the effects of genetic factors (Quantitative Trait Loci or QTLs) causing differences in abdominal bristle number between high and low selection lines of D. melanogaster. Results of this work suggest that, although quantitative traits may be affected by a large number of loci, a few loci may account for much of the variation present in a trait at any given time. Many of the factors had large sex specific allelic effects, and there was evidence for strong epistasis between the mapped factors. The observed biological properties of the mapped factors of this experiment are currently not incorporated into the standard models dealing with the maintenance of quantitative variation and selection response which generally assume loci of equal effect, additivity over loci, and equal allelic effects in males and females. Are mapped factors variants at candidate loci? It is important to determine if loci mutable to alleles of large effect (i.e., classic laboratory mutants) are also loci which harbour naturally occurring alleles of relatively small effect, and thus contribute to standing variation in morphological traits. If this is indeed the case, it will be relatively easy to move from mapped QTLs to actual genetic loci affecting a character. The development of the Drosophila peripheral nervous system (i.e., bristles are actually sensilla), has received a great deal of attention from developmental biologists, and has resulted in the identification and characterization of many of the genes involved in bristle patterning and formation. These loci are likely candidates for harbouring naturally occurring variants which contribute to bristle variation. Mapped factors coincide with the positions of a number of likely candidate loci (e.g., ASC, bb, emc, h, Dl, E(spl)), which suggests the candidate gene approach is promising. By adapting complementation testing and deficiency mapping to quantitative traits it is possible to show that in many cases mapped factors of the selection experiment are either allelic to or acting close in the same genetic pathways as these candidate loci. How much standing genetic variation in natural populations is attributable to loci of large effect? A problem with QTL mapping studies is that it is impossible to know the frequency of alleles at a mapped QTL in a natural population (by virtue of mapping being between a pair of lines). An alternative approach for characterizing a QTL is to associate DNA sequence variation at a candidate locus with phenotypic variation using a set of naturally occurring alleles at a candidate locus. This 'bottom up' approach eliminates the need to speculate about the distribution of allelic effects in natural populations based on data obtained from a cross, as the alleles examined are a random sample from a natural population. A number of experiments I have been involved in have found associations between polymorphisms at candidate loci and variation in bristle number. Similar studies for other candidate loci are also nearing completion (e.g., emc, h, H, E(spl), the ASC, and N). In addition to the above empirical aspects of associations studies, I am also interested in developing statistical techniques appropriate for the data this work generates. These methods may result in more accurate estimates of the frequency, effect, and location of factors that contribute to continuous variation than are currently available. What is the molecular genetic basis underlying alleles at QTLs? It is of interest to determine the nature of DNA sequence variants which give rise to alleles of quantitative effect, and eventually understand phenotypic evolution at the level of the individual loci that developmentally create a character. Properties (e.g., likelihood of fixation, mutation rates, and effects which are tissue specific) of different types of variants at QTLs (e.g., transposable element insertions, amino acid substitutions, and variation in DNA binding motifs) will have important evolutionary implications. For example, if mapped QTL allelic variants are due to transposable element insertions they are likely to have taxa specific evolutionary dynamics. Whereas, if variants are due to length variation of simple repeats in regulatory regions, then QTLs may have high intrinsic mutation rates which would have bearing on models of mutation selection balance. Experiments that address the molecular basis of continuous variation may provide useful new insights into long term phenotypic evolution which would not be obtainable by analyzing the problem at an organismic level. Future Directions: For some evolutionary questions estimates of the frequencies and effects associated with QTLs will suffice, for others knowing the actual molecular nature of polymorphisms that give rise to quantitative variation will be important. If the mutation-selection balance hypothesis is not sufficient to explain the maintenance of bristle variation, there are a number of competing models of natural selection which purport to explain balanced polymorphisms (e.g., negative pleiotropy, heterosis, genotype by environment interaction, and genotype by sex interaction). Experiments can be carried out which will refute or support each of these hypotheses given knowledge of the molecular nature of quantitative variation. Thus, an important goal of future work is the eventual molecular characterization of variants at neurogenic candidate genes which potentially cause naturally occurring variation in bristle number. The identification of the molecular variants responsible for quantitative genetic variation will allow the frequency of these variants to be estimated in different populations and species, and will also allow tests of hypotheses concerning the selective forces responsible for maintaining phenotypic differences within and between populations. It will also be important in the future to examine the generality of any conclusions that emerge from the work on Drosophila bristles in a number of other characters and organisms. Thus, although Drosophila will be a tool central to my research program in the foreseeable future, I am also interested in studying quantitative genetics in other organisms, especially those in which phenotypic variation has potentially measurable ecological consequence. |
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| Publications |
Long, A.D., R.F. Lyman, C.H. Langley and T.F.C. Mackay. 1997. Two sites in the Delta gene region contribute to naturally occurring variation in bristle number in Drosophila melanogaster. Submitted. |
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Long, A.D., M.N. Grote, and C.H. Langley. 1997. Genetic analysis of complex diseases (Technical Comment). Science 275: 1328. |
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Long, A.D., S.L. Mullaney, T.F.C Mackay, and C.H. Langley. 1996. Genetic interactions between naturally occurring alleles at quantitative trait loci and mutant alleles at candidate loci affecting bristle number in Drosophila melanogaster. Genetics 144: 1497-1510. |
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Long, A.D., S.L. Mullaney, L.A. Reid, J.D. Fry, C.H. Langley, and T.F.C. Mackay. 1995. High resolution mapping of genetic factors affecting abdominal bristle number in Drosophila melanogaster. Genetics 139: 1273-1291. |
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Long, A.D. and R.S. Singh. 1995. Molecules vs. morphology: The detection of selection acting on morphological characters along a cline in Drosophila melanogaster. Heredity 74: 569-595. |
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Lai, C., R.F. Lyman, A.D. Long, C.H. Langley, and T.F.C. Mackay. 1994. Naturally occurring variation in bristle number associated with molecular variation at the scabrous locus in Drosophila melanogaster. Science 266: 1697-1702. |
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| Link to this profile | http://www.faculty.uci.edu/profile.cfm?faculty_id=4563 | |
| Last updated | 08/23/2005 | |