Mutation, asexual reproduction and genetic load: A study in three parts

My dissertation addresses mutation and complex mating systems (models of mating systems that include outcrossing, selfing, and asexual reproduction) in three distinct chapters. Chapter 2 discusses the direct estimation of mutation rates for di-nucleotide microsatellite markers in the model genetic organism, Arabidopsis thaliana. Chapter 3 describes an empirical study that estimates quantitative genetic variance components, genetic diversity, and inbreeding depression/inbreeding load for a predominately asexual population of Mimulus guttatus. This study also fits different evolutionary models to the empirical data to determine which model best describes the population. Chapter 4 is a theoretical investigation of the effects asexual reproduction, outcrossing and selfing on the average number of deleterious mutations per gamete and inbreeding load for infinite and finite populations. The study utilizes both Infinite (an infinite number of genetic loci and an infinite population size) and Finite (a small number of genetic loci and a variety of small population sizes) computer simulations. These simulations incorporate different meiotic and mitotic mutation rates, varying degrees of dominance and differing strengths of selection

The Gonium pectorale genome demonstrates co-option of cell cycle regulation during the evolution of multicellularity

Citation: Hanschen, E. R., Marriage, T. N., Ferris, P. J., Hamaji, T., Toyoda, A., Fujiyama, A., . . . Olson, B. (2016). The Gonium pectorale genome demonstrates co-option of cell cycle regulation during the evolution of multicellularity. Nature Communications, 7, 10. doi:10.1038/ncomms11370Additional Authors: Anderson, J.;Bakaric, R.;Luria, V.;Karger, A.;Kirschner, M. W.;Durand, P. M.;Michod, R. E.;Nozaki, H.The transition to multicellularity has occurred numerous times in all domains of life, yet its initial steps are poorly understood. The volvocine green algae are a tractable system for understanding the genetic basis of multicellularity including the initial formation of cooperative cell groups. Here we report the genome sequence of the undifferentiated colonial alga, Gonium pectorale, where group formation evolved by co-option of the retinoblastoma cell cycle regulatory pathway. Significantly, expression of the Gonium retinoblastoma cell cycle regulator in unicellular Chlamydomonas causes it to become colonial. The presence of these changes in undifferentiated Gonium indicates extensive group-level adaptation during the initial step in the evolution of multicellularity. These results emphasize an early and formative step in the evolution of multicellularity, the evolution of cell cycle regulation, one that may shed light on the evolutionary history of other multicellular innovations and evolutionary transitions

Sequence of the Gonium pectorale mating locus reveals a complex and dynamic history of changes in volvocine algal mating haplotypes

Citation: Hamaji, T., Mogi, Y., Ferris, P. J., Mori, T., Miyagishima, S., Kabeya, Y., . . . Nozaki, H. (2016). Sequence of the Gonium pectorale mating locus reveals a complex and dynamic history of changes in volvocine algal mating haplotypes. G3: Genes, Genomes, Genetics, 6(5), 1179-1189. doi:10.1534/g3.115.026229Additional Authors: Nozaki, H.Sex-determining regions (SDRs) or mating-type (MT) loci in two sequenced volvocine algal species, Chlamydomonas reinhardtii and Volvox carteri, exhibit major differences in size, structure, gene content, and gametolog differentiation. Understanding the origin of these differences requires investigation of MT loci from related species. Here, we determined the sequences of the minus and plus MT haplotypes of the isogamous 16-celled volvocine alga, Gonium pectorale, which is more closely related to the multicellular V. carteri than to C. reinhardtii. Compared to C. reinhardtiiMT, G. pectoraleMT is moderately larger in size, and has a less complex structure, with only two major syntenic blocs of collinear gametologs. However, the gametolog content of G. pectoraleMT has more overlap with that of V. carteriMT than with C. reinhardtiiMT, while the allelic divergence between gametologs in G. pectorale is even lower than that in C. reinhardtii. Three key sex-related genes are conserved in G. pectorale MT: GpMID and GpMTD1 in MT-, and GpFUS1 in MT+. GpFUS1 protein exhibited specific localization at the plus-gametic mating structure, indicating a conserved function in fertilization. Our results suggest that the G. pectorale-V. carteri common ancestral MT experienced at least one major reformation after the split from C. reinhardtii, and that the V. carteri ancestral MT underwent a subsequent expansion and loss of recombination after the divergence from G. pectorale. These data begin to polarize important changes that occurred in volvocine MT loci, and highlight the potential for discontinuous and dynamic evolution in SDRs. © 2016 Hamaji et al

Data from: Fine-mapping nicotine resistance loci in Drosophila using a multiparent advanced generation inter-cross population

Animals in nature are frequently challenged by toxic compounds, from those that occur naturally in plants as a defense against herbivory, to pesticides used to protect crops. On exposure to such xenobiotic substances, animals mount a transcriptional response, generating detoxification enzymes and transporters that metabolize and remove the toxin. Genetic variation in this response can lead to variation in the susceptibility of different genotypes to the toxic effects of a given xenobiotic. Here we use Drosophila melanogaster to dissect the genetic basis of larval resistance to nicotine, a common plant defense chemical and widely used addictive drug in humans. We identified quantitative trait loci (QTL) for the trait using the DSPR (Drosophila Synthetic Population Resource), a panel of multiparental advanced intercross lines. Mapped QTL collectively explain 68.4% of the broad-sense heritability for nicotine resistance. The two largest-effect loci—contributing 50.3 and 8.5% to the genetic variation—map to short regions encompassing members of classic detoxification gene families. The largest QTL resides over a cluster of ten UDP-glucuronosyltransferase (UGT) genes, while the next largest QTL harbors a pair of cytochrome P450 genes. Using RNA-seq we measured gene expression in a pair of DSPR founders predicted to harbor different alleles at both QTL and showed that Ugt86Dd, Cyp28d1, and Cyp28d2 had significantly higher expression in the founder carrying the allele conferring greater resistance. These genes are very strong candidates to harbor causative, regulatory polymorphisms that explain a large fraction of the genetic variation in larval nicotine resistance in the DSPR

Nicotine Resistance Phenotypes (A population)

This file contains nicotine resistance measures for a large number of A lines from the Drosophila Synthetic Population Resource (DSPR, www.FlyRILs.org). Line identifiers are presented in the "patRIL" column, and phenotypes are presented in the "NicotineViability" column. Together with genotype data and analytical R code this file allows users to generate the QTL mapping results presented in Marriage et al. for the A population of DSPR RILs

DSPR Genotypes (B population)

This file contains genotypes for the population B RILs (Recombination Inbred Lines) of the DSPR (Drosophila Synthetic Population Resource). The genotypes were originally published in King et al. (Genome Research 2012, 22:1558-66) and are also available at www.FlyRILs.org (Data Release 2 - HMM Results for pB RILs at regularly spaced 10 kb intervals). The genotypes are derived from a Hidden Markov Model (HMM) at regularly spaced 10KB positions along the Drosophila melanogaster genome. There are no column headers in the file. Columns are: chromosome, genome position, line identifier, 36 columns of founder genotype probabilities, and 8 columns of additive probabilities. The precise names for each of the columns are listed in the analysis R code file for population B. Together with this code, and the nicotine resistance phenotype scores, a user can recapitulate the QTL mapping from Marriage et al

DSPR Genotypes (A population)

This file contains genotypes for the population A RILs (Recombination Inbred Lines) of the DSPR (Drosophila Synthetic Population Resource). The genotypes were originally published in King et al. (Genome Research 2012, 22:1558-66) and are also available at www.FlyRILs.org (Data Release 2 - HMM Results for pA RILs at regularly spaced 10 kb intervals). The genotypes are derived from a Hidden Markov Model (HMM) at regularly spaced 10KB positions along the Drosophila melanogaster genome. There are no column headers in the file. Columns are: chromosome, genome position, line identifier, 36 columns of founder genotype probabilities, and 8 columns of additive probabilities. The precise names for each of the columns are listed in the analysis R code file for population A. Together with this code, and the nicotine resistance phenotype scores, a user can recapitulate the QTL mapping from Marriage et al

R script for QTL analysis (A population)

This R script allows a user to read in genotype data for the DSPR (Drosophila Synthetic Population Resource, FlyRILs.org) and nicotine resistance phenotype data, and recapitulate the QTL mapping results presented in Marriage et al. for the "A" population of DSPR RILs

R script for QTL analysis (B population)

This R script allows a user to read in genotype data for the DSPR (Drosophila Synthetic Population Resource, FlyRILs.org) and nicotine resistance phenotype data, and recapitulate the QTL mapping results presented in Marriage et al. for the "B" population of DSPR RILs