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1.  Endogenous ROS levels in C. elegans under exogenous stress support revision of oxidative stress theory of life-history tradeoffs 
The oxidative stress theory of life-history tradeoffs states that oxidative stress caused by damaging free radicals directly underpins tradeoffs between reproduction and longevity by altering the allocation of energetic resources between these tasks. We test this theory by characterizing the effects of exogenous oxidative insult and its interaction with thermal stress and diet quality on a suite of life-history traits and correlations in Caenorhabditis elegans nematodes. We also quantify demographic aging rates and endogenous reactive oxygen species (ROS) levels in live animals.
Our findings indicate a tradeoff between investment in reproduction and antioxidant defense (somatic maintenance) consistent with theoretical predictions, but correlations between standard life-history traits yield little evidence that oxidative stress generates strict tradeoffs. Increasing oxidative insult, however, shows a strong tendency to uncouple positive phenotypic correlations and, in particular, to reduce the correlation between reproduction and lifespan. We also found that mild oxidative insult results in lower levels of endogenous ROS accompanied by hormetic changes in lifespan, demographic aging, and reproduction that disappear in combined-stress treatments--consistent with the oxidative stress theory of aging.
Our findings demonstrate that oxidative stress is a direct contributor to life-history trait variation and that traditional tradeoffs are not necessary to invoke oxidative stress as a mediator of relationships between life-history traits, supporting previous calls for revisions to theory.
PMCID: PMC4222818  PMID: 25056725
Aging; Fitness; Free radicals; Lifespan; Resource allocation
2.  Using Mitogenomic and Nuclear Ribosomal Sequence Data to Investigate the Phylogeny of the Xiphinema americanum Species Complex 
PLoS ONE  2014;9(2):e90035.
Nematodes within the Xiphinema americanum species complex are economically important because they vector nepoviruses which cause considerable damage to a variety of agricultural crops. The taxonomy of X. americanum species complex is controversial, with the number of putative species being the subject of debate. Accurate phylogenetic knowledge of this group is highly desirable as it may ultimately reveal genetic differences between species. For this study, nematodes belonging to the X. americanum species complex, including potentially mixed species populations, were collected from 12 geographically disparate locations across the U.S. from different crops and in varying association with nepoviruses. At least four individuals from each population were analyzed. A portion of the 18S nuclear ribosomal DNA (rDNA) gene was sequenced for all individuals while the internal transcribed spacer region 1 (ITS1) of rDNA was cloned and 2 to 6 clones per individual were sequenced. Mitochondrial genomes for numerous individuals were sequenced in parallel using high-throughput DNA sequencing (HTS) technology. Phylogenetic analysis of the 18S rDNA revealed virtually identical sequences across all populations. Analysis of ITS1 rDNA sequences revealed several well-supported clades, with some degree of congruence with geographic location and viral transmission, but also numerous presumably paralogous sequences that failed to form clades with other sequences from the same population. Analysis of mitochondrial DNA (mtDNA) indicated the presence of three distinct monophyletic clades of X. americanum species complex nematodes. Two clades contained nematodes found in association with nepovirus and the third contained divergent mtDNA sequences from three nematode populations from the western U.S. where nepovirus was absent. The inherent heterogeneity in ITS1 rDNA sequence data and lack of informative sites in 18S rDNA analysis suggests that mtDNA may be more useful in sorting out the taxonomic confusion of the X. americanum species complex.
PMCID: PMC3937401  PMID: 24587203
3.  A Broadly Implementable Research Course in Phage Discovery and Genomics for First-Year Undergraduate Students 
mBio  2014;5(1):e01051-13.
Engaging large numbers of undergraduates in authentic scientific discovery is desirable but difficult to achieve. We have developed a general model in which faculty and teaching assistants from diverse academic institutions are trained to teach a research course for first-year undergraduate students focused on bacteriophage discovery and genomics. The course is situated within a broader scientific context aimed at understanding viral diversity, such that faculty and students are collaborators with established researchers in the field. The Howard Hughes Medical Institute (HHMI) Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science (SEA-PHAGES) course has been widely implemented and has been taken by over 4,800 students at 73 institutions. We show here that this alliance-sourced model not only substantially advances the field of phage genomics but also stimulates students’ interest in science, positively influences academic achievement, and enhances persistence in science, technology, engineering, and mathematics (STEM) disciplines. Broad application of this model by integrating other research areas with large numbers of early-career undergraduate students has the potential to be transformative in science education and research training.
Engagement of undergraduate students in scientific research at early stages in their careers presents an opportunity to excite students about science, technology, engineering, and mathematics (STEM) disciplines and promote continued interests in these areas. Many excellent course-based undergraduate research experiences have been developed, but scaling these to a broader impact with larger numbers of students is challenging. The Howard Hughes Medical Institute (HHMI) Science Education Alliance Phage Hunting Advancing Genomics and Evolutionary Science (SEA-PHAGES) program takes advantage of the huge size and diversity of the bacteriophage population to engage students in discovery of new viruses, genome annotation, and comparative genomics, with strong impacts on bacteriophage research, increased persistence in STEM fields, and student self-identification with learning gains, motivation, attitude, and career aspirations.
PMCID: PMC3950523  PMID: 24496795
4.  Natural variation in Caenorhabditis briggsae mitochondrial form and function suggests a novel model of organelle dynamics 
Mitochondrion  2012;13(1):44-51.
Mitochondrial functioning and morphology are known to be connected through cycles of organelle fusion and fission that depend upon mitochondrial membrane potential (ΔΨM); however, we lack an understanding of the features and dynamics of natural mitochondrial populations. Using data from our recent study of univariate mitochondrial phenotypic variation in Caenorhabditis briggsae nematodes, we analyzed patterns of phenotypic correlation for 24 mitochondrial traits. Our findings support a role for ΔΨM in shaping mitochondrial dynamics, but no role for mitochondrial ROS. Further, our study suggests a novel model of mitochondrial population dynamics dependent upon cellular environmental context and with implications for mitochondrial genome integrity.
PMCID: PMC3566285  PMID: 23269324
complex I; electron transport chain; membrane potential; mitochondrial dynamics; nad5Δ; reactive oxygen species
5.  Evolution of a Higher Intracellular Oxidizing Environment in Caenorhabditis elegans under Relaxed Selection 
PLoS ONE  2013;8(6):e65604.
We explored the relationship between relaxed selection, oxidative stress, and spontaneous mutation in a set of mutation-accumulation (MA) lines of the nematode Caenorhabditis elegans and in their common ancestor. We measured steady-state levels of free radicals and oxidatively damaged guanosine nucleosides in the somatic tissues of five MA lines for which nuclear genome base substitution and GC-TA transversion frequencies are known. The two markers of oxidative stress are highly correlated and are elevated in the MA lines relative to the ancestor; point estimates of the per-generation rate of mutational decay (ΔM) of these measures of oxidative stress are similar to those reported for fitness-related traits. Conversely, there is no significant relationship between either marker of oxidative stress and the per-generation frequencies of base substitution or GC-TA transversion. Although these results provide no direct evidence for a causative relationship between oxidative damage and base substitution mutations, to the extent that oxidative damage may be weakly mutagenic in the germline, the case for condition-dependent mutation is advanced.
PMCID: PMC3679170  PMID: 23776511
6.  In Vivo Quantification Reveals Extensive Natural Variation in Mitochondrial Form and Function in Caenorhabditis briggsae 
PLoS ONE  2012;7(8):e43837.
We have analyzed natural variation in mitochondrial form and function among a set of Caenorhabditis briggsae isolates known to harbor mitochondrial DNA structural variation in the form of a heteroplasmic nad5 gene deletion (nad5Δ) that correlates negatively with organismal fitness. We performed in vivo quantification of 24 mitochondrial phenotypes including reactive oxygen species level, membrane potential, and aspects of organelle morphology, and observed significant among-isolate variation in 18 traits. Although several mitochondrial phenotypes were non-linearly associated with nad5Δ levels, most of the among-isolate phenotypic variation could be accounted for by phylogeographic clade membership. In particular, isolate-specific mitochondrial membrane potential was an excellent predictor of clade membership. We interpret this result in light of recent evidence for local adaptation to temperature in C. briggsae. Analysis of mitochondrial-nuclear hybrid strains provided support for both mtDNA and nuclear genetic variation as drivers of natural mitochondrial phenotype variation. This study demonstrates that multicellular eukaryotic species are capable of extensive natural variation in organellar phenotypes and highlights the potential of integrating evolutionary and cell biology perspectives.
PMCID: PMC3429487  PMID: 22952781
7.  Selfish Little Circles: Transmission Bias and Evolution of Large Deletion-Bearing Mitochondrial DNA in Caenorhabditis briggsae Nematodes 
PLoS ONE  2012;7(7):e41433.
Selfish DNA poses a significant challenge to genome stability and organismal fitness in diverse eukaryotic lineages. Although selfish mitochondrial DNA (mtDNA) has known associations with cytoplasmic male sterility in numerous gynodioecious plant species and is manifested as petite mutants in experimental yeast lab populations, examples of selfish mtDNA in animals are less common. We analyzed the inheritance and evolution of mitochondrial DNA bearing large heteroplasmic deletions including nad5 gene sequences (nad5Δ mtDNA), in the nematode Caenorhabditis briggsae. The deletion is widespread in C. briggsae natural populations and is associated with deleterious organismal effects. We studied the inheritance patterns of nad5Δ mtDNA using eight sets of C. briggsae mutation-accumulation (MA) lines, each initiated from a different natural strain progenitor and bottlenecked as single hermaphrodites across generations. We observed a consistent and strong drive toward higher levels of deletion-bearing molecules in the heteroplasmic pool of mtDNA after ten generations of bottlenecking. Our results demonstrate a uniform transmission bias whereby nad5Δ mtDNA accumulates to higher levels relative to intact mtDNA in multiple genetically diverse natural strains of C. briggsae. We calculated an average 1% per-generation transmission bias for deletion-bearing mtDNA relative to intact genomes. Our study, coupled with known deleterious phenotypes associated with high deletion levels, shows that nad5Δ mtDNA are selfish genetic elements that have evolved in natural populations of C. briggsae, offering a powerful new system to study selfish mtDNA dynamics in metazoans.
PMCID: PMC3409194  PMID: 22859984
8.  The worm in the world and the world in the worm 
BMC Biology  2012;10:57.
Caenorhabditis elegans is a preeminent model organism, but the natural ecology of this nematode has been elusive. A four-year survey of French orchards published in BMC Biology reveals thriving populations of C. elegans (and Caenorhabditis briggsae) in rotting fruit and plant stems. Rather than being simply a 'soil nematode', C. elegans appears to be a 'plant-rot nematode'. These studies signal a growing interest in the integrated genomics and ecology of these tractable animals.
See research article
PMCID: PMC3382423  PMID: 22731915
9.  Variation in Base-Substitution Mutation in Experimental and Natural Lineages of Caenorhabditis Nematodes 
Genome Biology and Evolution  2012;4(4):513-522.
Variation among lineages in the mutation process has the potential to impact diverse biological processes ranging from susceptibilities to genetic disease to the mode and tempo of molecular evolution. The combination of high-throughput DNA sequencing (HTS) with mutation-accumulation (MA) experiments has provided a powerful approach to genome-wide mutation analysis, though insights into mutational variation have been limited by the vast evolutionary distances among the few species analyzed. We performed a HTS analysis of MA lines derived from four Caenorhabditis nematode natural genotypes: C. elegans N2 and PB306 and C. briggsae HK104 and PB800. Total mutation rates did not differ among the four sets of MA lines. A mutational bias toward G:C→A:T transitions and G:C→T:A transversions was observed in all four sets of MA lines. Chromosome-specific rates were mostly stable, though there was some evidence for a slightly elevated X chromosome mutation rate in PB306. Rates were homogeneous among functional coding sequence types and across autosomal cores, arms, and tips. Mutation spectra were similar among the four MA line sets but differed significantly when compared with patterns of natural base-substitution polymorphism for 13/14 comparisons performed. Our findings show that base-substitution mutation processes in these closely related animal lineages are mostly stable but differ from natural polymorphism patterns in these two species.
PMCID: PMC3342874  PMID: 22436997
base substitution; mutation rate; mutation spectrum; nematode
10.  Evolution of Caenorhabditis Mitochondrial Genome Pseudogenes and Caenorhabditis briggsae Natural Isolates 
Molecular Biology and Evolution  2009;27(5):1087-1096.
Although most metazoan mitochondrial genomes are highly streamlined and encode little noncoding DNA outside of the “AT” region, the accumulation of mitochondrial pseudogenes and other types of noncoding DNA has been observed in a growing number of animal groups. The nematode species Caenorhabditis briggsae harbors two mitochondrial DNA (mtDNA) pseudogenes, named Ψnad5-1 and Ψnad5-2, presumably derived from the nad5 protein-coding gene. Here, we provide an in-depth analysis of mtDNA pseudogene evolution in C. briggsae natural isolates and related Caenorhabditis species. Mapping the observed presence and absence of the pseudogenes onto phylogenies suggests that Ψnad5-1 originated in the ancestor to C. briggsae and its recently discovered outcrossing relative species Caenorhabditis sp. 5 and Caenorhabditis sp. 9. However, Ψnad5-1 was not detected in Caenorhabditis sp. 9 natural isolates, suggesting a lineage-specific loss of this pseudogene in this species. Our results corroborated the previous finding that Ψnad5-2 originated within C. briggsae. The observed pattern of mitochondrial pseudogene gain and loss in Caenorhabditis was inconsistent with predictions of the tandem duplication–random loss model of mitochondrial genome evolution and suggests that intralineage recombination–like mechanisms might play a major role in Caenorhabditis mtDNA evolution. Natural variation was analyzed at the pseudogenes and flanking mtDNA sequences in 141 geographically diverse C. briggsae natural isolates. Although phylogenetic analysis placed the majority of isolates into the three previously established major intraspecific clades of C. briggsae, two new and unexpected haplotypes fell outside of these conventional groupings. Ψnad5-2 copy number variation was observed among C. briggsae isolates collected from the same geographic site. Patterns of nucleotide diversity were analyzed in Ψnad5-1 and Ψnad5-2, and confidence intervals were found to overlap values from synonymous sites in protein-coding genes, consistent with neutral expectations. Our findings provide new insights into the mode and tempo of mitochondrial genome and pseudogene evolution both within and between Caenorhabditis nematode species.
PMCID: PMC2857805  PMID: 20026478
Caenorhabditis; mitochondrial genome; nucleotide diversity; phylogenetics; pseudogene
11.  Expanding the Diversity of Mycobacteriophages: Insights into Genome Architecture and Evolution 
Pope, Welkin H. | Jacobs-Sera, Deborah | Russell, Daniel A. | Peebles, Craig L. | Al-Atrache, Zein | Alcoser, Turi A. | Alexander, Lisa M. | Alfano, Matthew B. | Alford, Samantha T. | Amy, Nichols E. | Anderson, Marie D. | Anderson, Alexander G. | Ang, Andrew A. S. | Ares, Manuel | Barber, Amanda J. | Barker, Lucia P. | Barrett, Jonathan M. | Barshop, William D. | Bauerle, Cynthia M. | Bayles, Ian M. | Belfield, Katherine L. | Best, Aaron A. | Borjon, Agustin | Bowman, Charles A. | Boyer, Christine A. | Bradley, Kevin W. | Bradley, Victoria A. | Broadway, Lauren N. | Budwal, Keshav | Busby, Kayla N. | Campbell, Ian W. | Campbell, Anne M. | Carey, Alyssa | Caruso, Steven M. | Chew, Rebekah D. | Cockburn, Chelsea L. | Cohen, Lianne B. | Corajod, Jeffrey M. | Cresawn, Steven G. | Davis, Kimberly R. | Deng, Lisa | Denver, Dee R. | Dixon, Breyon R. | Ekram, Sahrish | Elgin, Sarah C. R. | Engelsen, Angela E. | English, Belle E. V. | Erb, Marcella L. | Estrada, Crystal | Filliger, Laura Z. | Findley, Ann M. | Forbes, Lauren | Forsyth, Mark H. | Fox, Tyler M. | Fritz, Melissa J. | Garcia, Roberto | George, Zindzi D. | Georges, Anne E. | Gissendanner, Christopher R. | Goff, Shannon | Goldstein, Rebecca | Gordon, Kobie C. | Green, Russell D. | Guerra, Stephanie L. | Guiney-Olsen, Krysta R. | Guiza, Bridget G. | Haghighat, Leila | Hagopian, Garrett V. | Harmon, Catherine J. | Harmson, Jeremy S. | Hartzog, Grant A. | Harvey, Samuel E. | He, Siping | He, Kevin J. | Healy, Kaitlin E. | Higinbotham, Ellen R. | Hildebrandt, Erin N. | Ho, Jason H. | Hogan, Gina M. | Hohenstein, Victoria G. | Holz, Nathan A. | Huang, Vincent J. | Hufford, Ericka L. | Hynes, Peter M. | Jackson, Arrykka S. | Jansen, Erica C. | Jarvik, Jonathan | Jasinto, Paul G. | Jordan, Tuajuanda C. | Kasza, Tomas | Katelyn, Murray A. | Kelsey, Jessica S. | Kerrigan, Larisa A. | Khaw, Daryl | Kim, Junghee | Knutter, Justin Z. | Ko, Ching-Chung | Larkin, Gail V. | Laroche, Jennifer R. | Latif, Asma | Leuba, Kohana D. | Leuba, Sequoia I. | Lewis, Lynn O. | Loesser-Casey, Kathryn E. | Long, Courtney A. | Lopez, A. Javier | Lowery, Nicholas | Lu, Tina Q. | Mac, Victor | Masters, Isaac R. | McCloud, Jazmyn J. | McDonough, Molly J. | Medenbach, Andrew J. | Menon, Anjali | Miller, Rachel | Morgan, Brandon K. | Ng, Patrick C. | Nguyen, Elvis | Nguyen, Katrina T. | Nguyen, Emilie T. | Nicholson, Kaylee M. | Parnell, Lindsay A. | Peirce, Caitlin E. | Perz, Allison M. | Peterson, Luke J. | Pferdehirt, Rachel E. | Philip, Seegren V. | Pogliano, Kit | Pogliano, Joe | Polley, Tamsen | Puopolo, Erica J. | Rabinowitz, Hannah S. | Resiss, Michael J. | Rhyan, Corwin N. | Robinson, Yetta M. | Rodriguez, Lauren L. | Rose, Andrew C. | Rubin, Jeffrey D. | Ruby, Jessica A. | Saha, Margaret S. | Sandoz, James W. | Savitskaya, Judith | Schipper, Dale J. | Schnitzler, Christine E. | Schott, Amanda R. | Segal, J. Bradley | Shaffer, Christopher D. | Sheldon, Kathryn E. | Shepard, Erica M. | Shepardson, Jonathan W. | Shroff, Madav K. | Simmons, Jessica M. | Simms, Erika F. | Simpson, Brandy M. | Sinclair, Kathryn M. | Sjoholm, Robert L. | Slette, Ingrid J. | Spaulding, Blaire C. | Straub, Clark L. | Stukey, Joseph | Sughrue, Trevor | Tang, Tin-Yun | Tatyana, Lyons M. | Taylor, Stephen B. | Taylor, Barbara J. | Temple, Louise M. | Thompson, Jasper V. | Tokarz, Michael P. | Trapani, Stephanie E. | Troum, Alexander P. | Tsay, Jonathan | Tubbs, Anthony T. | Walton, Jillian M. | Wang, Danielle H. | Wang, Hannah | Warner, John R. | Weisser, Emilie G. | Wendler, Samantha C. | Weston-Hafer, Kathleen A. | Whelan, Hilary M. | Williamson, Kurt E. | Willis, Angelica N. | Wirtshafter, Hannah S. | Wong, Theresa W. | Wu, Phillip | Yang, Yun jeong | Yee, Brandon C. | Zaidins, David A. | Zhang, Bo | Zúniga, Melina Y. | Hendrix, Roger W. | Hatfull, Graham F.
PLoS ONE  2011;6(1):e16329.
Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and Mycobacterium tuberculosis. All mycobacteriophages characterized to date are dsDNA tailed phages, and have either siphoviral or myoviral morphotypes. However, their genetic diversity is considerable, and although sixty-two genomes have been sequenced and comparatively analyzed, these likely represent only a small portion of the diversity of the mycobacteriophage population at large. Here we report the isolation, sequencing and comparative genomic analysis of 18 new mycobacteriophages isolated from geographically distinct locations within the United States. Although no clear correlation between location and genome type can be discerned, these genomes expand our knowledge of mycobacteriophage diversity and enhance our understanding of the roles of mobile elements in viral evolution. Expansion of the number of mycobacteriophages grouped within Cluster A provides insights into the basis of immune specificity in these temperate phages, and we also describe a novel example of apparent immunity theft. The isolation and genomic analysis of bacteriophages by freshman college students provides an example of an authentic research experience for novice scientists.
PMCID: PMC3029335  PMID: 21298013
12.  Natural variation in life history and aging phenotypes is associated with mitochondrial DNA deletion frequency in Caenorhabditis briggsae 
Mutations that impair mitochondrial functioning are associated with a variety of metabolic and age-related disorders. A barrier to rigorous tests of the role of mitochondrial dysfunction in aging processes has been the lack of model systems with relevant, naturally occurring mitochondrial genetic variation. Toward the goal of developing such a model system, we studied natural variation in life history, metabolic, and aging phenotypes as it relates to levels of a naturally-occurring heteroplasmic mitochondrial ND5 deletion recently discovered to segregate among wild populations of the soil nematode, Caenorhabditis briggsae. The normal product of ND5 is a central component of the mitochondrial electron transport chain and integral to cellular energy metabolism.
We quantified significant variation among C. briggsae isolates for all phenotypes measured, only some of which was statistically associated with isolate-specific ND5 deletion frequency. We found that fecundity-related traits and pharyngeal pumping rate were strongly inversely related to ND5 deletion level and that C. briggsae isolates with high ND5 deletion levels experienced a tradeoff between early fecundity and lifespan. Conversely, oxidative stress resistance was only weakly associated with ND5 deletion level while ATP content was unrelated to deletion level. Finally, mean levels of reactive oxygen species measured in vivo showed a significant non-linear relationship with ND5 deletion level, a pattern that may be driven by among-isolate variation in antioxidant or other compensatory mechanisms.
Our findings suggest that the ND5 deletion may adversely affect fitness and mitochondrial functioning while promoting aging in natural populations, and help to further establish this species as a useful model for explicit tests of hypotheses in aging biology and mitochondrial genetics.
PMCID: PMC3032685  PMID: 21226948
13.  Spontaneous Mutations Decrease Sensitivity of Gene Expression to Random Environmental Variation in Caenorhabditis elegans 
PLoS ONE  2010;5(1):e8750.
Biological phenotypes are described as “canalized” if they are robust to minor variation of environment and/or genetic background. The existence of a robust phenotype logically implies that some underlying mechanism must be variable, in the sense of “able to vary”, in order to compensate for variation in the environment and/or genetic effects. Several lines of evidence lead to the conclusion that deleterious mutations predictably render morphological, developmental, and life-history traits more sensitive to small random environmental perturbations - that is, mutations de-canalize the phenotype.
Methodology/Principal Findings
Using conventional dye-swap microarray methodology, we compared transcript abundance in a sample of >7,000 genes between four mutation accumulation (MA) lines of the nematode Caenorhabditis elegans and the common (unmutated) ancestor. There was significantly less environmental variance in the MA lines than in the ancestor, both among replicates of the same gene and among genes.
Deleterious mutations consistently decrease the within-line component of variance in transcript abundance, which is straightforwardly interpreted as reducing the sensitivity of gene expression to small random variation in the environment. This finding is consistent with the idea that underlying variability in gene expression might be mechanistically responsible for phenotypic robustness.
PMCID: PMC2807463  PMID: 20090917
14.  High Rate of Large Deletions in Caenorhabditis briggsae Mitochondrial Genome Mutation Processes 
Mitochondrial DNA (mtDNA) mutations underlie a variety of human genetic disorders and are associated with the aging process. mtDNA polymorphisms are widely used in a variety of evolutionary applications. Although mtDNA mutation spectra are known to differ between distantly related model organisms, the extent to which mtDNA mutation processes vary between more closely related species and within species remains enigmatic. We analyzed mtDNA divergence in two sets of 250-generation Caenorhabditis briggsae mutation-accumulation (MA) lines, each derived from a different natural isolate progenitor: strain HK104 from Okayama, Japan, and strain PB800 from Ohio, United States. Both sets of C. briggsae MA lines accumulated numerous large heteroplasmic mtDNA deletions, whereas only one similar event was observed in a previous analysis of Caenorhabditis elegans MA line mtDNA. Homopolymer length change mutations were frequent in both sets of C. briggsae MA lines and occurred in both intergenic and protein-coding gene regions. The spectrum of C. briggsae mtDNA base substitution mutations differed from the spectrum previously observed in C. elegans. In C. briggsae, the HK104 MA lines experienced many different base substitution types, whereas the PB800 lines displayed only C:G → T:A transitions, although the difference was not significant. Over half of the mtDNA base substitutions detected in the C. briggsae MA lines were in a heteroplasmic state, whereas all those previously characterized in C. elegans MA line mtDNA were fixed changes, indicating a narrower mtDNA bottleneck in C. elegans as compared with C. briggsae. Our results show that C. briggsae mtDNA is highly susceptible to large deletions and that the mitochondrial mutation process varies between Caenorhabditis nematode species.
PMCID: PMC2839355  PMID: 20333220
bottleneck; heteroplasmy; mutation-accumulation line; nematode
15.  Molecular evolution in Panagrolaimus nematodes: origins of parthenogenesis, hermaphroditism and the Antarctic species P. davidi 
As exemplified by the famously successful model organism Caenorhabditis elegans, nematodes offer outstanding animal systems for investigating diverse biological phenomena due to their small genome sizes, short generation times and ease of laboratory maintenance. Nematodes in the genus Panagrolaimus have served in comparative development and anhydrobiosis studies, and the Antarctic species P. davidi offers a powerful paradigm for understanding the biological mechanisms of extreme cold tolerance. Panagrolaimus nematodes are also unique in that examples of gonochoristic, hermaphroditic and parthenogenetic reproductive modes have been reported for members of this genus. The evolutionary origins of these varying reproductive modes and the Antarctic species P. davidi, however, remain enigmatic.
We collected nuclear ribosomal RNA gene and mitochondrial protein-coding gene sequences from diverse Panagrolaimus species and strains, including newly discovered isolates from Oregon, to investigate phylogenetic relationships in this nematode genus. Nuclear phylogenies showed that the species and strains historically identified as members of Panagrolaimus constitute a paraphyletic group, suggesting that taxonomic revision is required for Panagrolaimus and related nematode lineages. Strain-specific reproductive modes were mapped onto the molecular phylogeny to show a single origin of parthenogenesis from a presumably gonochoristic ancestor. The hermaphroditic strains were all placed outside a major monophyletic clade that contained the majority of other Panagrolaimus nematodes. Phylogenetic analyses of mitochondrial sequences showed that substantial molecular and geographic diversity exists within the clade of parthenogenetic strains. The Antarctic species P. davidi was found to be very closely related to two Panagrolaimus strains from southern California. Phylogenetic and molecular clock analyses suggested that P. davidi and the California strain PS1579 shared a common ancestor in the very recent evolutionary past.
Our study provides a phylogenetic framework for understanding the evolutionary origins and diversification patterns of varying reproductive modes within Panagrolaimus and important insights into the origin of the Antarctic species P. davidi. Panagrolaimus offers a powerful nematode model for understanding diverse evolutionary phenomena including the evolution of asexuality and the adaptive evolution of extreme cold tolerance.
PMCID: PMC2632994  PMID: 19149894
16.  Natural selection governs local, but not global, evolutionary gene coexpression networks in Caenorhabditis elegans 
BMC Systems Biology  2008;2:96.
Large-scale evaluation of gene expression variation among Caenorhabditis elegans lines that have diverged from a common ancestor allows for the analysis of a novel class of biological networks – evolutionary gene coexpression networks. Comparative analysis of these evolutionary networks has the potential to uncover the effects of natural selection in shaping coexpression network topologies since C. elegans mutation accumulation (MA) lines evolve essentially free from the effects of natural selection, whereas natural isolate (NI) populations are subject to selective constraints.
We compared evolutionary gene coexpression networks for C. elegans MA lines versus NI populations to evaluate the role that natural selection plays in shaping the evolution of network topologies. MA and NI evolutionary gene coexpression networks were found to have very similar global topological properties as measured by a number of network topological parameters. Observed MA and NI networks show node degree distributions and average values for node degree, clustering coefficient, path length, eccentricity and betweeness that are statistically indistinguishable from one another yet highly distinct from randomly simulated networks. On the other hand, at the local level the MA and NI coexpression networks are highly divergent; pairs of genes coexpressed in the MA versus NI lines are almost entirely different as are the connectivity and clustering properties of individual genes.
It appears that selective forces shape how local patterns of coexpression change over time but do not control the global topology of C. elegans evolutionary gene coexpression networks. These results have implications for the evolutionary significance of global network topologies, which are known to be conserved across disparate complex systems.
PMCID: PMC2596099  PMID: 19014554
17.  TileQC: A system for tile-based quality control of Solexa data 
BMC Bioinformatics  2008;9:250.
Next-generation DNA sequencing technologies such as Illumina's Solexa platform and Roche's 454 approach provide new avenues for investigating genome-scale questions. However, they also present novel analytical challenges that must be met for their effective application to biological questions.
Here we report the availability of tileQC, a tile-based quality control system for Solexa data written in the R language. TileQC provides a means of recognizing bias and error in Solexa output by graphically representing data generated by flow cell tiles. The data represented in the images is then made available in the R environment for further analysis and automation of error detection.
TileQC offers a highly adaptable and powerful tool for the quality control of Solexa-based DNA sequence data.
PMCID: PMC2443380  PMID: 18507856
18.  Muller's Ratchet and compensatory mutation in Caenorhabditis briggsae mitochondrial genome evolution 
The theory of Muller' Ratchet predicts that small asexual populations are doomed to accumulate ever-increasing deleterious mutation loads as a consequence of the magnified power of genetic drift and mutation that accompanies small population size. Evidence for Muller's Ratchet and knowledge on its underlying molecular mechanisms, however, are lacking for natural populations.
We characterized mitochondrial genome evolutionary processes in Caenorhabditis briggsae natural isolates to show that numerous lineages experience a high incidence of nonsynonymous substitutions in protein-coding genes and accumulate unusual deleterious noncoding DNA stretches with associated heteroplasmic function-disrupting genome deletions. Isolate-specific deletion proportions correlated negatively with nematode fecundity, suggesting that these deletions might negatively affect C. briggsae fitness. However, putative compensatory mutations were also observed that are predicted to reduce heteroplasmy levels of deleterious deletions. Paradoxically, compensatory mutations were observed in one major intraspecific C. briggsae clade where population sizes are estimated to be very small (and selection is predicted to be relatively weak), but not in a second major clade where population size estimates are much larger and selection is expected to be more efficient.
This study provides evidence that the mitochondrial genomes of animals evolving in nature are susceptible to Muller's Ratchet, suggests that context-dependent compensatory mutations can accumulate in small populations, and predicts that Muller's Ratchet can affect fundamental evolutionary forces such as the rate of mutation.
PMCID: PMC2279117  PMID: 18302772

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