02425nas a2200241 4500008004100000022002500041245011700066210006900183260001600252300001400268490000700282520163200289653001601921653003101937653001501968100002701983700002002010700002202030700002002052700002802072700002502100856005802125 2006 eng d a0022-2585, 1938-292800aSequencing of a New Target Genome: thePediculus humanus humanus(Phthiraptera: Pediculidae) Genome Project0 aSequencing of a New Target Genome theiPediculus humanus humanusi cNov-01-2006 a1103-11110 v433 a

The human body louse, Pediculus humanus humanus (L.), and the human head louse, Pediculus humanus capitis, belong to the hemimetabolous order Phthiraptera. The body louse is the primary vector that transmits the bacterial agents of louse-borne relapsing fever, trench fever, and epidemic typhus. The genomes of the bacterial causative agents of several of these aforementioned diseases have been sequenced. Thus, determining the body louse genome will enhance studies of host-vector-pathogen interactions. Although not important as a major disease vector, head lice are of major social concern. Resistance to traditional pesticides used to control head and body lice have developed. It is imperative that new molecular targets be discovered for the development of novel compounds to control these insects. No complete genome sequence exists for a hemimetabolous insect species primarily because hemimetabolous insects often have large (2,000 Mb) to very large (up to 16,300 Mb) genomes. Fortuitously, we determined that the human body louse has one of the smallest genome sizes known in insects, suggesting it may be a suitable choice as a minimal hemimetabolous genome in which many genes have been eliminated during its adaptation to human parasitism. Because many louse species infest birds and mammals, the body louse genome-sequencing project will facilitate studies of their comparative genomics. A 6-8× coverage of the body louse genome, plus sequenced expressed sequence tags, should provide the entomological, evolutionary biology, medical, and public health communities with useful genetic information.

10aPediculosis10areduced genomic complexity10aresistance1 aPittendrigh, Barry, R.1 aClark, Marshall1 aJohnston, Spencer1 aLee, Sang, Hong1 aRomero-Severson, Jeanne1 aDasch, Gregory, Alan uhttps://academic.oup.com/jme/article/43/6/1103/88908901585nas a2200181 4500008004100000022001400041245004900055210004700104260001600151300001200167490000800179520105200187100002001239700002101259700002001280700002701300856007601327 2013 eng d a0048-357500aHuman lice: Past, present and future control0 aHuman lice Past present and future control cJul-01-2013 a162-1710 v1063 a

Human lice represent one of the longest ectoparasitic relationships associated with mankind. Whereas the body louse vectors bacterial diseases that have killed millions, the head louse does not but represents an economic and social concern worldwide. A crisis exists in the control of lice due to the availability of only a few new pediculicides and the occurrence of resistance. In this review, we summarize data that validates the knockdown resistance mechanism (kdr) as the main cause of control failures to the pyrethrin/pyrethroid-based pediculicides and the molecular diagnostics used to determine kdr worldwide. New commercially-available pediculicide are discussed in terms of their use in sustainable resistance management approaches. Lastly, the optimization of dose, the timing of exposure, and the assessment of transcript levels during tolerance is used to identify detoxification genes that metabolize ivermectin as a proof of principle experiment, indicating that such an approach may allow proactive resistance management.

1 aClark, Marshall1 aYoon, Kyong, Sup1 aLee, Si, Hyeock1 aPittendrigh, Barry, R. uhttps://www.sciencedirect.com/science/article/abs/pii/S004835751300052702900nas a2200205 4500008004100000245010500041210006900146260001200215300000900227490000600236520224900242100001502491700001902506700002902525700002102554700002002575700002702595700001902622856005302641 2010 eng d00aGenotyping of Human Lice Suggests Multiple Emergences of Body Lice from Local Head Louse Populations0 aGenotyping of Human Lice Suggests Multiple Emergences of Body Li c03-2010 ae6410 v43 a

Background: Genetic analyses of human lice have shown that the current taxonomic classification of head lice (Pediculus humanus capitis) and body lice (Pediculus humanus humanus) does not reflect their phylogenetic organization. Three phylotypes of head lice A, B and C exist but body lice have been observed only in phylotype A. Head and body lice have different behaviours and only the latter have been involved in outbreaks of infectious diseases including epidemic typhus, trench fever and louse borne recurrent fever. Recent studies suggest that body lice arose several times from head louse populations.

Methods and Findings: By introducing a new genotyping technique, sequencing variable intergenic spacers which were selected from louse genomic sequence, we were able to evaluate the genotypic distribution of 207 human lice. Sequence variation of two intergenic spacers, S2 and S5, discriminated the 207 lice into 148 genotypes and sequence variation of another two intergenic spacers, PM1 and PM2, discriminated 174 lice into 77 genotypes. Concatenation of the four intergenic spacers discriminated a panel of 97 lice into 96 genotypes. These intergenic spacer sequence types were relatively specific geographically, and enabled us to identify two clusters in France, one cluster in Central Africa (where a large body louse outbreak has been observed) and one cluster in Russia. Interestingly, head and body lice were not genetically differentiated.

Conclusions: We propose a hypothesis for the emergence of body lice, and suggest that humans with both low hygiene and head louse infestations provide an opportunity for head louse variants, able to ingest a larger blood meal (a required characteristic of body lice), to colonize clothing. If this hypothesis is ultimately supported, it would help to explain why poor human hygiene often coincides with outbreaks of body lice. Additionally, if head lice act as a reservoir for body lice, and that any social degradation in human populations may allow the formation of new populations of body lice, then head louse populations are potentially a greater threat to humans than previously assumed.

1 aLi, Wenjun1 aOrtiz, Gabriel1 aFournier, Pierre-Edouard1 aGimenez, Gregory1 aReed, David, L.1 aPittendrigh, Barry, R.1 aRaoult, Didier uhttps://dx.plos.org/10.1371/journal.pntd.000064101897nas a2200229 4500008004100000245013400041210006900175260001400244300001400258490000700272520113000279100002101409700002601430700001701456700001601473700001601489700001701505700002701522700002001549700002001569856007801589 2011 eng d00aBrief exposures of human body lice to sublethal amounts of ivermectin over-transcribes detoxification genes involved in tolerance0 aBrief exposures of human body lice to sublethal amounts of iverm cSept 2011 a687 - 6990 v203 a

Transcriptional profiling results, using our non-invasive induction assay [short exposure intervals (2–5 h) to sub-lethal amounts of insecticides (<LD3 at 24 h) administered by stress reducing means (contact vs. immersion screen) and with induction assessed in a time frame when tolerance is still present (~LC90 in 2–4 h)], show that ivermectin-induced detoxification genes from body lice are identified by quantitative real-time PCR analyses.
Of the cytochrome P450 monooxygenase and ATP binding cassette transporter genes induced by ivermectin, CYP6CJ1, CYP9AG1, CYP9AG2 and PhABCC4 were respectively most significantly over-expressed, had high basal expression levels and were most closely related to genes from other organisms that metabolized insecticides, including ivermectin.
Injection of dsRNAs against either CYP9AG2 or PhABCC4 into non-induced female lice reduced their respective transcript level and resulted in increase sensitivity to ivermectin, indicating that these two genes are involved in the xenobiotic metabolism of ivermectin and in the production of tolerance.

1 aYoon, Kyong, Sup1 aStrycharz, Joseph, P.1 aBaek, J., H.1 aSun, Weilin1 aKim, J., H.1 aKang, J., S.1 aPittendrigh, Barry, R.1 aLee, Si, Hyeock1 aClark, Marshall uhttps://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2583.2011.01097.x03205nas a2200313 4500008004100000022001400041245005800055210005800113260001600171300001200187490000700199520223300206653006002439100002102499700001902520700002302539700002402562700001802586700002102604700002502625700002002650700002202670700002202692700002702714700003002741700002002771700002302791856007702814 2017 eng d a1063-515700aPhylogenomics from Whole Genome Sequences Using aTRAM0 aPhylogenomics from Whole Genome Sequences Using aTRAM cJan-01-2019 a786-7980 v663 a

Abstract.—Novel sequencing technologies are rapidly expanding the size of data sets that can be applied to phylogenetic studies. Currently the most commonly used phylogenomic approaches involve some form of genome reduction. While these approaches make assembling phylogenomic data sets more economical for organisms with large genomes, they reduce the genomic coverage and thereby the long-term utility of the data. Currently, for organisms with moderate to small genomes (<1000 Mbp) it is feasible to sequence the entire genome at modest coverage (10−30×). Computational challenges for handling these large data sets can be alleviated by assembling targeted reads, rather than assembling the entire genome, to produce a phylogenomic data matrix. Here we demonstrate the use of automated Target Restricted Assembly Method (aTRAM) to assemble 1107 single-copy ortholog genes from whole genome sequencing of sucking lice (Anoplura) and out-groups. We developed a pipeline to extract exon sequences from the aTRAM assemblies by annotating them with respect to the original target protein. We aligned these protein sequences with the inferred amino acids and then performed phylogenetic analyses on both the concatenated matrix of genes and on each gene separately in a coalescent analysis. Finally, we tested the limits of successful assembly in aTRAM by assembling 100 genes from close- to distantly related taxa at high to low levels of coverage.
Both the concatenated analysis and the coalescent-based analysis produced the same tree topology, which was consistent with previously published results and resolved weakly supported nodes. These results demonstrate that this approach is successful at developing phylogenomic data sets from raw genome sequencing reads. Further, we found that with coverages above 5−10×, aTRAM was successful at assembling 80–90% of the contigs for both close and distantly related taxa. As sequencing costs continue to decline, we expect full genome sequencing will become more feasible for a wider array of organisms, and aTRAM will enable mining of these genomic data sets for an extensive variety of applications, including phylogenomics.

10aaTRAM; gene assembly; genome sequencing; phylogenomics.1 aAllen, Julie, M.1 aBoyd, Bret, M.1 aNguyen, Nam-phuong1 aVachaspati, Pranjal1 aWarnow, Tandy1 aHuang, Daisie, I1 aGrady, Patrick, G.S.1 aBell, Kayce, C.1 aCronk, Quentin, C1 aMugisha, Lawrence1 aPittendrigh, Barry, R.1 aLeonardi, MarĂ­a, Soledad1 aReed, David, L.1 aJohnson, Kevin, P. uhttps://academic.oup.com/sysbio/article-lookup/doi/10.1093/sysbio/syw10502004nas a2200265 4500008004100000022001400041245007000055210006900125260001600194490000800210520120700218653001601425653001301441653002401454653002401478653001401502100002301516700002101539700001701560700002201577700002001599700001801619700002701637856007401664 2014 eng d a0962-845200aRates of genomic divergence in humans, chimpanzees and their lice0 aRates of genomic divergence in humans chimpanzees and their lice cJan-08-20140 v2813 a

The rate of DNA mutation and divergence is highly variable across the tree of life. However, the reasons underlying this variation are not well understood. Comparing the rates of genetic changes between hosts and parasite lineages that diverged at the same time is one way to begin to understand differences in genetic mutation and substitution rates. Such studies have indicated that the rate of genetic divergence in parasites is often faster than that of their hosts when comparing single genes. However, the variation in this relative rate of molecular evolution across different genes in the genome is unknown. We compared the rate of DNA sequence divergence between humans, chim- panzees and their ectoparasitic lice for 1534 protein-coding genes across their genomes. The rate of DNA substitution in these orthologous genes was on average 14 times faster for lice than for humans and chimpanzees. In addition, these rates were positively correlated across genes. Because this correlation only occurred for substitutions that changed the amino acid, this pattern is probably produced by similar functional constraints across the same genes in humans, chimpanzees and their ectoparasites.

10acoevolution10agenomics10ahosts and parasites10amolecular evolution10aPediculus1 aJohnson, Kevin, P.1 aAllen, Julie, M.1 aOlds, B., P.1 aMugisha, Lawrence1 aReed, David, L.1 aPaige, K., N.1 aPittendrigh, Barry, R. uhttp://rspb.royalsocietypublishing.org/cgi/doi/10.1098/rspb.2013.217401948nas a2200217 4500008004100000245016400041210006900205260000900274300001600283490000700299520115900306100002301465700001901488700001701507700002001524700002801544700002501572700002301597700002701620856008301647 2003 eng d00aTranscriptome identification of putative genes involved in protein catabolism and innate immune response in human body louse (Pediculicidae: Pediculus humanus)0 aTranscriptome identification of putative genes involved in prote c2003 a1135 - 11430 v333 a

Genomics information relating to human body lice is surprisingly scarce, and this has constrained studies of their physiology, immunology and vector biology. To identify novel body louse genes, we used engorged adult lice to generate a cDNA library. Initially, 1152 clones were screened for inserts, edited for removal of vector sequences and base pairs of poor quality, and viewed for splicing variations, gene families and polymorphism. Computational methods identified 506 inferred open reading frames including the first predicted louse defensin. The inferred defensin aligns well with other insect defensins and has highly conserved cysteine residues, as are known for other defensin sequences. Two cysteine and five serine proteinases were categorized according to their inferred catalytic sites. We also discovered seven putative ubiquitin-pathway genes and four iron metabolizing deduced enzymes. Finally, glutathione-S-transferases and cytochrome P450 genes were among the detoxification enzymes found. Results from this first systematic effort to discover human body louse genes should promote further studies in Phthiraptera and lice.

1 aPedra, Joao, H. F.1 aBrandt, Amanda1 aLi, Hong-Mei1 aWesterman, Rick1 aRomero-Severson, Jeanne1 aPollack, Richard, J.1 aMurdock, Larry, L.1 aPittendrigh, Barry, R. uhttps://www.sciencedirect.com/science/article/pii/S0965174803001334?via%3Dihub