Evolution; Genetics; Biometry
Work in our lab focuses in two areas: evolutionary genetics and applied biostatistics. All of our genetic work uses Drosophila melanogaster as a model system. Our earlier genetic work centered on the process of speciation. Experiments demonstrate that speciation (i.e. the evolution of complete reproductive isolation) can rapidly be induced in the laboratory without allopatry, and that this process can feasibly operate in nature.
More recent work centered on the evolution of dimorphic sex chromosomes, especially the Y chromosome. Recent experiment in our lab have recapitulated the early stages in the evolution of the Y chromosome and indicate that sexually antagonist alleles (i.e. those favored in one sex while disfavored in the other) have played an important role in causing both the suppressed recombination and degeneration of the Y.
Our most recent work focused on coevolution between the sexes. Comparative studies and theory indicate that, in non-monogamous species, antagonistic coevolution between the sexes may frequently occur. The opportunity for such sexually antagonistic coevolution is particularly high in species that have internal fertilization, since males and females are in direct chemical communication owing to the fact that males place many seminal fluid proteins into the female along with the sperm. Studies in other labs have demonstrated that, in Drosophila melanogaster, seminal proteins benefit males by reducing his mate's propensity to remate with another male and by increasing her egg-laying rate. When females do remate, the seminal fluid proteins also play a key role in sperm competition. These benefits to males are in sharp contrast to a deleterious impact on females; seminal fluid acts, as a byproduct of their other functions in females, as a low-level toxin. Males and females can become locked in an evolutionary "arms race" as males evolve anatomy, behavior and seminal proteins that advance their reproductive advantage at the expense of their mates. Females can respond by evolutionary modifying their behavior, physiology, and anatomy to ameliorate such changes in the male. In a recent experiment we stopped females from evolving and let males continue to evolve in response to a static female phenotype. The males rapidly evolved increased reproductive success but this male advantage resulted in reduced female survival, due to males remating with females more frequently and, in one replicate, due to the males seminal fluid becoming more toxic to females. Our new experiments focus on sperm competition and sexual selection.
Besides our current work on male/female coevolution, we are experimentally looking at the adaptive significance of sexual recombination. In a previous study we used the X (recombining) and Y (non-recombining) sex chromosome as a model system to study the adaptive significance of sex. By constructing synthetic Y chromosomes, with a Drosophila melanogaster model system, we were able to show that the clonally propagated Y chromosome deteriorates as a direct result of its lack of recombination (in large part via the Muller's ratchet process). Experiments now in progress center on the whole genome and contrast the relative rates of adaptation in sexual and asexual laboratory populations.
Summary of research by W. R. Rice (see CV for references)
My research career began in the area of applied statistics and wildlife biology during my Master's research at Ohio State University (Rice 1977). Although I did not continue research in wildlife biology, I have continued to do research in the area of applied biostatistics. During my Ph.D. research I specialized in the general area of behavior ecology and specifically on the sensory ecology and foraging behavior of the Northern Harrier (Rice 1982; 1983c). It was not until my postdoctoral studies at UC-Davis that I began research in evolutionary genetics, which has continued to the present. My research has focused on 8 major areas which are briefly described below.
My research on speciation began in the early 1980's and it focused initially on the question of whether the evolution of reproductive isolation required allopatry (the separation of populations in space or time, which causes gene flow to be absent). I first used multilocus simulation modeling to show that the evolution of reproductive isolation without allopatry was more genetically plausible when reproductive isolation evolved indirectly as a correlated trait rather than directly due to selection for positive assortative mating (Rice 1984a). I next tested the feasibility of this speciation mechanism with a pair of laboratory experiments using a D. melanogaster model system (Rice 1985a). The experiments demonstrated that strong reproductive isolation could rapidly evolve as a correlated character in response to divergent selection on habitat preference when organisms mated locally in their preferred habitats. I next synthesized the past theory and experiments on non-allopatric speciation in a review (Rice 1987c) and used this synthesis to design a new set of experiments in which complete reproductive isolation (i.e., speciation) was predicted to evolve in response to divergent selection on habitat preference. The second set of experiments was carried out and, as predicted by theory, complete reproduction isolation was observed to evolve in response to divergent selection on habitat preference (Rice & Salt 1988a; 1990a). These experiments were important because no other laboratory experiment, besides the non-repeatable experiments of Today & Gibson (1964), had completely recapitulated the speciation process without allopatry. I next wrote, in collaboration with my graduate student Ellen Hostert, an extensive review and synthesis of past experiments attempting to duplicate the speciation process under controlled laboratory conditions, and integrated these results into the body of theory that had developed concerning speciation (Rice & Hostert 1993b). The next stage of my work on speciation concerned the process of allopatric speciation. I specifically sought to identify the processes that were responsible for causing the genetic divergence that leads to the evolution of reproductive isolation. I first carried out a set of experiments that indicated that males and females can continually coevolve due to a self-reinforcing evolutionary arms race (Rice 1996a). I next surveyed the literature and found extensive empirical evidence that perpetual antagonistic coevolution between the sexes is likely to be widespread in both plants and animals and that it contributes importantly to the evolution of reproductive isolation among allopatric populations (Rice 1998b; Rice & Holland 1997a; 1999b; Holland and Rice 1998d).
Interspecific antagonistic coevolution (Red Queen process)
My research on antagonistic coevolution between species began with an extensive review and synthesis of data from agricultural and medical studies (Rice 1983b). These studies collectively indicated that coevolution between a species and its enemies can provide strong selection for sexual recombination. The work extended earlier studies by W. Hamelton, D. Levin, and J. Jainike by showing that parent-offspring pathogen transmission can be an important factor selecting for sexual recombination. This literature review and synthesis motivated a set of field experiments using a scale-insect/sugar-pine model system that demonstrated that a plant pest can rapidly evolved resistance to its host, that clonal reproduction increased the susceptibility of offspring to the pest that had colonized the parents, and that a single round of sexual recombination protected offspring from the pathogens that were specifically adapted to the genetic defenses of the parents (Rice 1983a). I next developed a bacteria-phage (E. coli/M13) model system to study coevolution between a host and its pathogens. Despite extensive work with this system most of my research was not published due to my need to focus on other aspects of my research. I eventually collaborated with Jim Bull concerning this model system, and due mainly to his efforts, the utility of the model system was established (Bull, Molineux, & Rice 1991b). Lastly, I collaborated with Jim Bull on a general model for the evolution of interspecific cooperation (Bull & Rice 1991a).
The evolution of dimorphic sex chromosomes
This research focused on the processes that caused a normal pair of autosomes to evolve into dimorphic X & Y sex chromosomes. The work began with a theoretical study concerning the evolution of sexual dimorphism (Rice 1984b). This work indicated that sex chromosomes facilitated the accumulation of genetic variation that is favored in one sex and disfavored in the other sex (sexually antagonistic alleles). Further theoretical study indicated that sexually antagonistic alleles may also play a key role in the initial step in sex chromosome evolution (the evolution of a sex determining locus, Rice 1986), in selecting for the gradual breakdown in recombination between primitive sex chromosomes (Rice 1987a), and leading to the decay in genetic function of the nonrecombining Y (or W) sex chromosome (Rice 1987b). These theoretical studies motivated an experiment to test the hypothesis that the evolution of a gender-determining locus will lead to the accumulation of sexually antagonistic alleles at tightly linked loci (Rice 1992). In these experiments, done with a D. melanogaster model system, I created new, synthetic female-determining genes. As predicted by theory, the experiments demonstrated that the presence of these nascent gender-determining genes led to the accumulation of sexually antagonistic alleles at tightly linked loci. My earlier theoretical work, in addition to that of many other researchers, also motivated an experiment to test the hypothesis that lack of recombination accelerates the accumulation of small-effect deleterious alleles on a primitive Y sex chromosome (a phenomenon known as Muller's ratchet, or more generally, retrogressive evolution). Experiments were performed that created giant synthetic neo-Y chromosomes in a D. melanogaster model system (Rice 1994a). As predicted by theory, these nonrecombining chromosomes accumulated harmful genetic variation faster than control chromosomes that continued to recombine. I next wrote an extensive review and synthesis of the theory and experiments concerning the evolution of the Y sex chromosome (Rice 1996b). This review motivated a new experiment in which the whole genome of D. melanogaster was made to segregate like a giant neo-Y sex chromosome. Theory predicted that these synthetic, male-limited sex chromosomes should accumulate male-benefit/female detriment sexually antagonistic variation, and this was found to be the case (Rice 1998a). These experiments also supported the hypothesis that perpetual coevolution between the Y and the rest of the genome will lead to recurrent selective sweeps on the Y chromosome that would lead to its decay via to genetic hitchhiking. I next collaborated with a postdoc in my laboratory, Adam Chippindale, to assay the amount of standing genetic variation of the Y chromosome of D. melanogaster (Chippindale & Rice 2001c). Because of the relatively small number of genes know to reside on the Y chromosome of D. melanogaster, it was expected that little or no genetic variation for fitness would be found. In contrast we found substantial fitness variation on the Y but most of this variation was estimated to be non-additive. Lastly, I recently wrote a review and synthesis, in collaboration with Adam Chippindale, concerning coevolution between Y-linked genes and sexually antagonistic genetic variation that is located on the X and autosomes (Rice & Chippindale 2002b).
Interlocus Contest Evolution (ICE) and Antagonistic coevolution between the sexes
My earlier work, and that of others, on antagonistic coevolution between species motivated a new hypothesis that genes in the genome of a species can coevolve in an antagonistic manner that is analogous to the antagonistic coevolution that occurs between a species and its enemies (the Red Queen process). It is well established that most genes in the genome coevolve in a mutualistic manner owing to the fact that their evolutionary fate is jointly determined by the fitness of the organism within which they are expressed. It is also possible, however, for genes in the same genome to evolve antagonistically. The best known case of this process concerns genes that causes meiotic drive. These genes typically increase in frequency at the expense of the fitness of the other genes in the genome. There is also considerable evidence that transposable genetic elements represent a class of genes that increase in frequency at the expense of the fitness of the rest of the genome. More recently David Haig provided evidence that intragenomic conflict (via sex-specific genetic imprinting) also can lead to evolutionary discord within the genome of a single species. My research, in addition to that by Robert Trivers, Geoff Parker, and Mary Jane West-Eberhard, has provided evidence for a fourth type of antagonistic coevolution within the genome of a single species that I refer to as intergenomic conflict. In this case alleles at two or more loci mediate contests, such as competition, between interacting individuals. In the simplest case of two interacting loci, the fitness of an allele at one locus (locus-A -e.g., a gene coding for a protein that influences the rate at which the sperm binds and penetrates an unfertilized egg) depends on the allele present at an interacting locus (locus-B - e.g., a receptor protein on the egg's surface). Suppose that a new allele evolved at the A-locus that caused a sperm to penetrate the egg faster and thereby increased its competitive ability in the context of sperm competition. The allele would be favored by selection and, in the simplest case, increase to fixation in the population. But if sperm penetrate the egg too rapidly then polyspermy will occur at an elevated rate and this will select for a new allele at the B-locus (egg receptor locus) to slow down sperm penetration. Once a new B allele (egg receptor) evolves that slows down sperm penetration, this will select for a new counteracting allele at the A locus (sperm penetration). Under some circumstances this dynamic can lead to stable polymorphism or a stable limit cycle, but in many contexts it leads to perpetual antagonistic coevolution between the interacting loci. Such perpetual antagonistic coevolution between loci that is driven by intergenomic conflict is referred to as Interlocus Contest Evolution (ICE) . My first work in this area was an experiment with a D. melanogaster model system, in which I used cytogenetic constructs to create a population in which males could adapted to females but females could not coevolve (Rice 1996). In these experiments the males rapidly evolved in response to the evolutionarily tethered females, and this adaptation by the males was at the expense of the fitness of their mates. This initial experimental work led to an extensive literature review detailing how ICE could drive genetic change that promoted the evolution of reproductive isolation among allopatric populations (Rice 1998b-this work was delay in publication for 2 years owing to delays in publishing the edited volume in which it was published). I next, in collaboration with my graduate student Brett Holland, expanded the theoretical treatment of ICE in reviews of the plant and animal literature (Rice & Holland 1997a; 1999b; Holland & Rice 1998d; Rice 2000). This synthesis and review of the literature led to a key prediction concerning intersexual ICE: Theory predicts that intersexual intergenomic conflict is reversed when there is random mating and monogamy. To test this prediction Brett Holland and I constructed monogamous and promiscuous populations of D. melanogaster and followed their evolutionary change over 50 generations (Holland & Rice 1999a). As predicted by theory the antagonistic coevolution that had been observed when only males could evolve in the context of a promiscuous mating system (Rice 1996) was converted to mutualistic coevolution between the sexes when monogamy was experimentally enforced. Lastly, I tested the hypothesis that intersexual ICE can perpetually drive the decay of the Y sex chromosome (via genetic hitchhiking) by continually selecting for new Y-linked alleles (Rice 1998a).
Intersexual Ontogenetic Conflict
Males and females represent different environments in which genes can be expressed. Several lines of evidence, including recent micro-array analyses, indicates that most genes in the genome are expressed in both sexes. Because the sexes are selected to do many fundamentally different biological functions, different alleles may be optimal for each sex. As a consequence, selection in one sex can detract form adaptation in the other sex. We (Adam Chippindale and I) refer to this potential genetic discord between the sexes as intersexual ontogenetic conflict because it is generally manifest during development when the expression of sexually antagonistic alleles (those favored in one sex but disfavored in the other sex) moves one sex toward its optimal phenotype while moving the other sex away from its phenotypic optimum. My theoretical research on ontogenetic conflict began in the 1980's while I was studying the evolution of sex chromosomes (Rice 1984b; 1986; 1987a; 1987b). This theoretical research motivated an experiment to test whether this type of genetic variation was common in the genome of D. melanogaster, as was described in the above section on sex chromosomes (Rice 1992). The experiments provided evidence that sexually antagonistic variation may be quite common. To further test this idea I collaborated with a postdoc in my lab (Adam Chippindale ) and a graduate student in my lab (Jonathan Gibson) to carryout a more definitive experiment (Chippindale, Gibson, & Rice, 2001d). In these experiments we assayed the total fitness of 40 random genomes (i.e., full sets of genes, or genomic haplotypes, excluding the small number of genes on the dot chromosome) by expressing them in both males in females in an average of 75 different genetic backgrounds. We found high levels of additive genetic variance within each sex for total fitness, as well as its two sequential components (juvenile fitness [egg-to-adult viability], and adult fitness [male mating & fertilization success and female fecundity]). In the juvenile stage, where gender role are similar, we found a strong positive correlation for fitness. But in the adult stage, where gender role diverge, we found a negative correlation, indicating that, averaged over the entire genome, genotypes that were optimal for males were suboptimal for females and visa versa. My earlier theoretical work (Rice 1984b) predicted that much of the sexually antagonistic fitness variation would reside on the X chromosome. My laboratory tested this prediction by a new experiment that assayed the fitness variation on the X chromosome alone (Gibson, Chippindale, & Rice, 2002a). As predicted, most of the genome-wide sexually antagonistic fitness variation mapped to the X chromosome. Currently we are investigating the phenotypes that mediate ontogenetic conflict and we are better resolving the relative contributions of different parts of the genome.
Adaptive Significance of Sexual Recombination
This line of my research began in the early 1980's when I wrote an extensive literature review of agricultural and medical research to evaluate the hypothesis that parent-offspring pathogen transmission was an important factor favoring sexual compared to asexual reproduction (Rice 1983b). As described in an earlier section, this theoretical work was tested with a field experiment using a scale-insect/sugar pine model system (Rice 1983a). I next used sex chromosomes as a model system to study the adaptive significance of recombination. These homologous chromosomes are derived from a common autosomal pair in which one member evolved to stop recombining while the other retained recombination. Most of this research was described earlier in the section on sex chromosomes (see especially Rice 1987b; Rice 1992; Rice 1994b; and Rice 1996b). I next carried out theoretical work concerning mutational load in recombining vs. nonrecombining species (Rice 1998c). To date this work has not led to experimental analysis, largely because my lab is not properly equipped to study 'pathway epistasis', but I hope to collaborate on an experimental test of this hypothesis in the future. The major predictions from my theoretical work on sexual recombination (as well as that of many other researchers, such as D. Charlesworth, B. Charlesworth, N. Barton, J. Peck, M. Lynch) was that recombining species (or chromosomes) should accumulate beneficial mutations faster than recombining species and that they should accumulate mildly deleterious mutations slower, i.e., recombination speeds the rate of progressive evolution and it slows the rate of retrogressive evolution. My experiments with D. melanogaster in the early 1990's on the process of Muller's ratchet demonstrated that recombination slows the rate of accumulation of mildly deleterious mutations on synthetic recombining X chromosome compared to synthetic nonrecombining Y chromosomes. In the early 2000's I tested the other prediction in a D. melanogaster model system, i.e., that the accumulation of beneficial mutations is faster, on average, on recombining compared to nonrecombining chromosomes (Rice & Chippindale 2001a). These experiments demonstrated that recombination increases the probability of fixation of new beneficial mutations. Lastly, I recently wrote a review of the literature concerning controlled laboratory experiments testing hypotheses for the adaptive significance of sexual recombination (Rice 2002b). This synthesis of past studies was much in need because the past laboratory experiments concerning the adaptive significance of sexual recombination are dispersed among 5 decades of research in many unrelated journals, and this scattering has obscured the fact that considerable progress has been made in deciphering the advantages of recombination.
Hemiclonal Genetic Analysis
Many of the experiments described above used a technique in which my lab uses male Drosophila as cloning vehicles. In the past, balancer chromosomes were used to suppress recombination and thereby permit individual chromosomes to be analyzed as a unit. The problem with this technique is that the balancer chromosomes only work well when present alone --using more than one balancer at a time causes each individual balancer to lose its effectiveness, and when all chromosomes are balanced simultaneously the technique works very poorly. Because male D. melanogaster do not have intrachromosomal recombination, but they do recombine via segregation of chromosomes, my lab has devised cytogenetic constructs (clone-generator females) that allow us to clonally propagate and amplify all, or any subset, of the genome. Clonal propagation is achieved by making a group of target chromosomes (or a single chromosome) cosegregate like a nascent, male-limited, nonrecombining Y chromosome. There are many application for this technique, but the major use that we have exploited is the measurement of fitness variation of the whole genome and its constituent parts. Using this technique, we have been able to measure fitness under normal levels of heterozygosity, and thereby avoid the pitfalls associated with measuring fitness under unnatural levels of inbreeding (homozygosity). In order to use this technique we needed to be able to measure fitness under the environmental conditions to which the flies have adapted. To accomplish this we have brought into the laboratory a large sample of flies from a natural population (with the generous help of Larry Harshman) and then let this population adapt to a rigorous laboratory environment for over 300 generations at large size (N> 1800 each generation). We now have established a large outbred base population that we are analyzing under the environmental conditions to which it is adapted.
During my training during my Masters and Ph.D. research I focused jointly in biological and statistical analysis. Over the years I encountered statistical testing contexts that were relevant to biological research but that were not congruent with established statistical tests. In these cases I developed new statistical tests to fill the missing gaps. Some of these research projects were done in collaboration with Steve Gaines. Specifically I (with Steve Gaines where noted) have developed new techniques for: i) contingency analysis when sample sizes are small (CBET test; Rice 1988d; 1988e; 1990d); ii) combining independent tests that evaluate the same hypothesis (Consensus combined probability test; Rice 1990c); iii) incorporating ordered alternative hypotheses into the context of ANOVA and similar multi-population tests (Ordered heterogeneity test; Gaines and Rice 1990b; Rice & Gaines 1994b; 1994c); iv) evaluating family-wide statistical significance (Rice 1989a); v) an alternative to one-sided statistical testing (Rice and Gaines 1994d); and vi) ANOVA when cell variances are unequal (Rice and Gaines 1989b; 1993a).
- Pischedda, A. and W. R. Rice. Partitioning sexual selection into its mating success and fertilization success components Proc. Nat. Acad. Sci. USA 109:2049-2053.
- Rice W. R. The evolution of an enigmatic human trait: false beliefs due to pseudo-solution traps. The American Naturalist 179:557-66.
- Rice, W. R., U. Friberg, and S. Gavrilets. Homosexuality as a consequence of epigenetically canalized sexual development. Quarterly Review Biology In Press.
- Friberg, U., P. M. Miller, A. D. Stewart and W. R. Rice. Mechanisms promoting the long-term persistence of a Wolbachia infection in a laboratory-adapted population of Drosophila melanogaster. PLoS ONE 6(1): e16448. doi:10.1371/journal.pone.0016448.
- Turner, T. A. D. Stewart, A. T. Fields, W. R. Rice, and A. M. Tarone. Population-Based Resequencing of Experimentally Evolved Populations Reveals the Genetic Basis of Body Size Variation in Drosophila melanogaster. PLoS Genetics 7(3): e1001336. doi:10.1371/journal.pgen.1001336
- Bachtrog, D., Kirkpatrick, M, Mank, J. E., McDaniel, S. F., Pires, J. C., Rice, W. R., and Valenzuela N. Are all sex chromosomes created equal? Trends in Genetics 27: 350-357.
- Friberg, U, A. D. Stewart, and W. R. Rice. Empirical evidence for son-killing X chromosomes and the operation of SA-zygotic drive. PLoS ONE 6(8): e23508. doi:10.1371/journal.pone.0023508.
- Friberg, U, A. D. Stewart, and W. R. Rice. X and Y chromosome linked paternal effects on a life history trait. Biology Letters 8:71-73.
- Long, T A. F., A. Pischedda, R. V. Nichols, W. R. Rice. The timing of mating influences reproductive success in Drosophila melanogaster:
- Rice, W. R., U. Friberg, and S. Gavrilets. The evolution of sex-specific grandparental harm. Proc. Royal Soc.-Biol. 277: 2727-35.