I am investigating genes responsible for differences in cellular stress resistance and rates of aging among individuals in natural populations of microscopic soil worms.
Why would I do that?
Humans are now experiencing greater chances of living to old ages and are living longer than they have in recorded history (Vaupel et al. 1998). Given this increase in lifespan, a major task for biogerontologists is to find ways to increase “healthspan” – those years of life that are active and healthy. Genetic manipulations of model organisms in the laboratory have been crucial in identifying genes that can affect lifespan and stress resistance in model organisms. For example, we now have a sizeable list of genes suspected to modulate aging via inputs from insulin-dependent signaling, caloric restriction, fat storage, metabolism, heat shock response, and stress resistance via insulin/insulin-like growth factor signaling (IIS) and other signal transduction pathways, and resistance to molecular stress (Antebi 2007; Hughes and Reynolds 2005).
Despite the rapid progress being made in the genetics and genomics of aging, it is unclear whether candidate aging genes identified via mutation studies play any role in the differences in lifespan among individuals. In addition, there is a growing consensus that one of the most promising methods for advancing our understanding of complex biological processes will be to examine how those processes function in a natural system (Oleksiak et al. 2001; Partridge and Gems 2006; Vijg and Suh 2005). For the genetic basis of longevity and human disease, this understanding may be crucial, yielding information on natural allelic or gene expression differences that produce individuals that are healthier longer. Characterizing the genetics of lifespan in natural populations may identify new candidate genes relevant to natural populations, tell us whether previously identified candidate aging genes contribute to variation in longevity, and develop our understanding of the gene networks that interact to produce the complex aging phenotype.
The nematode Caenorhabditis elegans has been one of the most powerful systems for uncovering conserved mechanisms by which the aging process can be manipulated. It is a well-developed model system with flexible genetic/genomic tools, yet recent studies show that it lacks significant genetic diversity (Barriere and Felix 2005; Haber et al. 2005; Sivasundar and Hey 2003; Sivasundar and Hey 2005), and thus it will serve as a poor model for studying variation in aging. Caenorhabditis remanei, a close evolutionary relative of C. elegans, is an ideal complement to C. elegans as a natural system. It is readily collected in nature, is easily kept in the laboratory, and has a three-day generation time. It has a relatively small genome (approx. 135 Mb) that has been sequenced and is awaiting assembly. It is amenable to the same laboratory and genetic manipulations as C. elegans. Like C. elegans, C. remanei can be frozen, allowing parental and descendant generations to be tested at the same time, and allowing large numbers of collections to be maintained with little effort. C. remanei may make a better model for human aging because it has both males and females. Most importantly, in contrast to the poor genetic variance found within the “selfing” C. elegans, C. remanei has been shown to harbor significant amounts of natural molecular genetic (Graustein et al. 2002; Jovelin et al. 2003) and quantitative genetic (Reynolds & Phillips 2013) variation in longevity within and among populations . The genetic variation of C. remanei and its genomic tractability make it the ideal model system for studying the genetic complexities of individual variation in aging.
Currently I am an assistant professor in the Department of Biology at William Jewell College in Liberty, Missouri and collaborating with Patrick Phillips and Bill Cresko in the Institute of Ecology and Evolution at the University of Oregon. We are working jointly to dissect the evolutionary genetics of complex traits, from molecule to genetic pathway to network of pathways on up to cellular, organismal and population-wide phenotypes. The field of evolutionary biology is uniquely positioned to combine traditional quantitative genetic methods with cutting edge high throughput genetic and genomic tools to dissect a key complex trait in both evolutionary biology and medicine: aging.
I am currently developing several key molecular genetic/genomic tools for C. remanei and in the process of identifying ecologically relevant “healthspan” genes from one or more natural C. remanei populations.
Sikkink, Kristin L., Rose M. Reynolds, Catherine M. Ituarte, William A. Cresko & Patrick C. Phillips. 2014. Rapid evolution of phenotypic plasticity and shifting thresholds of genetic assimilation in the nematode Caenorhabditis remanei. G3: Genes|Genomes|Genetics. 4(6):1103-12. doi: 10.1534/g3.114.010553.
Reynolds, Rose M. & Patrick C. Phillips. 2013. Natural variation for lifespan and stress response in the nematode Caenorhabditis remanei. PLoS One. 8(4): e58212.
Anderson, Jennifer L.,* Rose M. Reynolds*, Levi T. Morran, Julie Tolman-Thompson, and Patrick C. Phillips. 2011. Experimental evolution reveals antagonistic pleiotropy in reproductive timing but not life span in Caenorhabditis elegans. Journal of Gerontology, Series A: Biological Sciences. 66(12): 1300-1308.
Reynolds, Rose M., Sara Temiyasathit, Melissa M. Reedy, Elizabeth A. Ruedi, Jenny M. Drnevich, Jeff Leips and Kimberly A. Hughes 2007. Age specificity of inbreeding load inDrosophila melanogaster and implications for the evolution of late-life mortality plateaus. Genetics. 177(1): 587-595.
Hughes,Kimberly A., & Rose M. Reynolds. 2005. Evolutionary and mechanistic theories of aging. Annual Review of Entomology. 50: 421-445.
Hughes, Kimberly A., Julie A. Alipaz, Jenny M. Drnevich, and Rose M. Reynolds. 2002. A test of evolutionary theories of aging. Proceedings of the National Academy of Sciences. 99(22): 14286-14291.
Antebi, A., 2007 Genetics of aging in Caenorhabditis elegans. Plos Genetics 3: 1565-1571.
Barriere, A., and M. A. Felix, 2005 High local genetic diversity and low outcrossing rate inCaenorhabditis elegans natural populations. Current Biology 15: 1176-1184.
Graustein, A., J. M. Gaspar, J. R. Walters and M. F. Palopoli, 2002 Levels of DNA polymorphism vary with mating system in the nematode genus Caenorhabditis. Genetics 161: 99-107.
Haber, M., M. Schungel, A. Putz, S. Muller, B. Hasert et al., 2005 Evolutionary history ofCaenorhabditis elegans inferred from microsatellites: Evidence for spatial and temporal genetic differentiation and the occurrence of outbreeding. Molecular Biology and Evolution 22: 160-173.
Hughes, K. A., and R. M. Reynolds, 2005 Evolutionary and mechanistic theories of aging. Annual Review of Entomology 50: 421-445.
Jovelin, R., B. C. Ajie and P. C. Phillips, 2003 Molecular evolution and quantitative variation for chemosensory behaviour in the nematode genus Caenorhabditis. Molecular Ecology 12: 1325-1337.
Oleksiak, M. F., K. J. Kolell and D. L. Crawford, 2001 Utility of natural populations for microarray analyses: Isolation of genes necessary for functional genomic studies. Marine Biotechnology 3: S203-S211.
Partridge, L., and D. Gems, 2006 Beyond the evolutionary theory of ageing, from functional genomics to evo-gero. Trends in Ecology & Evolution 21: 334-340.
Sivasundar, A., and J. Hey, 2003 Population genetics of Caenorhabditis elegans: The paradox of low polymorphism in a widespread species. Genetics 163: 147-157.
Sivasundar, A., and J. Hey, 2005 Sampling from natural populations with RNAi reveals high outcrossing and population structure in Caenorhabditis elegans. Current Biology 15: 1598-1602.
Vaupel, J. W., J. R. Carey, K. Christensen, T. E. Johnson, A. I. Yashin et al., 1998 Biodemographic trajectories of longevity. Science 280: 855-860.
Vijg, J., and Y. Suh, 2005 Genetics of longevity and aging. Annual Review of Medicine 56: 193-212.