COMPARATIVE STUDY OF GENOMIC FEATURES OF EVOLUTIONARILY YOUNG GENE DUPLICATES

Gene duplication is considered a major contributor to genome evolution and functional diversity. Differences in genomic features (such as structural resemblance, transcriptional orientation, and genomic location) between members of a gene duplicate pair may indicate the possible duplication mechanisms, as well as the evolutionary fates the paralogs may experience. In addition to these genomic features, molecular genetic features, such as differences in codon usage and expression levels may provide further insight into functional changes between paralogs. In this dissertation, multiple genomic analyses were conducted in order to evaluate the differences in genomic and genetic properties between duplicate copies in order to understand the effect duplication mechanisms may have on the divergence of duplicate pairs. Chapter Two focuses on differing patterns of sequence asymmetry, codon usage, and gene expression levels between the members of gene duplicate pairs belonging to two different populations of paralogs in Saccharomyces cerevisiae: ohnologs, which arose via a whole genome duplication (WGD), and small segmental duplication (SSD) paralogs. It is shown that ohnologs have more highly conserved gene order (synteny) relative to SSD paralogs, despite their greater evolutionary age. Within SSD pairs, the derived paralog (the copy with lower synteny) seems to evolve faster, simultaneously exhibiting a lower CIA value and lower expression levels relative to the ancestral copy. While synteny and evolutionary rate differences were not coupled in ohnolog pairs, the relationship between evolutionary rate asymmetry, CAI, and expression levels was similar to that observed in SSD pairs. These results indicate that codon usage contributes to rate asymmetry in the evolution of gene duplicates in both, ohnologs and SSD paralogs, while differences in synteny (as experienced by SSD pairs, but not very young ohnologs) only affects rate asymmetry in SSD pairs. This may imply relaxed selection on codon usage and the expression of derived copies, potentially leading to the acquisition of novel functions over time. Chapters Three and Four focus on the effects of structural resemblance and other genomic features on young gene duplicate pairs within the Homo sapiens (human) and Pan troglodytes (chimpanzee) genomes. The results imply that the majority of gene duplicates in both species are structurally complete duplications, encompassing the entire coding region of a gene. The chimpanzee genome additionally contains a large fraction (46%) of retrotransposed young gene duplicates relative to the human genome (13%) which may be due to differences in genome architecture, such as mobile element content between the two genomes. While RNA-mediated processes lead to a majority of inter-chromosomal paralogs, DNA-mediated paralogs reside largely on the same chromosome, in which case inter-paralog distance does not increase over time. These results in conjunction with results of previous studies in nematodes, yeast, and flies, suggest that the structural resemblance types and location of duplicates are closely linked to the duplication mechanism by which paralog pairs arise. This is also true for closely related species, as illustrated by the comparison of the human and chimpanzee genomes. The above studies illustrate the relationship duplication span (as illustrated in Chapter Two) and mechanisms (illustrated in Chapters Three and Four) have on the location, synteny, structural resemblance types, and functionality of gene duplicates in different genomes. The findings imply that differences in mechanisms between species can have significant effects on the genome evolution and divergence between even closely related taxa

Early evolutionary history and genomic features of gene duplicates in the human genome

BACKGROUND: Human gene duplicates have been the focus of intense research since the development of array-based and targeted next-generation sequencing approaches in the last decade. These studies have primarily concentrated on determining the extant copy-number variation from a population-genomic perspective but lack a robust evolutionary framework to elucidate the early structural and genomic characteristics of gene duplicates at emergence and their subsequent evolution with increasing age. RESULTS: We analyzed 184 gene duplicate pairs comprising small gene families in the draft human genome with 10 % or less synonymous sequence divergence. Human gene duplicates primarily originate from DNA-mediated events, taking up genomic residence as intrachromosomal copies in direct or inverse orientation. The distribution of paralogs on autosomes follows random expectations in contrast to their significant enrichment on the sex chromosomes. Furthermore, human gene duplicates exhibit a skewed gradient of distribution along the chromosomal length with significant clustering in pericentromeric regions. Surprisingly, despite the large average length of human genes, the majority of extant duplicates (83 %) are complete duplicates, wherein the entire ORF of the ancestral copy was duplicated. The preponderance of complete duplicates is in accord with an extremely large median duplication span of 36 kb, which enhances the probability of capturing ancestral ORFs in their entirety. With increasing evolutionary age, human paralogs exhibit declines in (i) the frequency of intrachromosomal paralogs, and (ii) the proportion of complete duplicates. These changes may reflect lower survival rates of certain classes of duplicates and/or the role of purifying selection. Duplications arising from RNA-mediated events comprise a small fraction (11.4 %) of all human paralogs and are more numerous in older evolutionary cohorts of duplicates. CONCLUSIONS: The degree of structural resemblance, genomic location and duplication span appear to influence the long-term maintenance of paralogs in the human genome. The median duplication span in the human genome far exceeds that in C. elegans and yeast and likely contributes to the high prevalence of complete duplicates relative to structurally heterogeneous duplicates (partial and chimeric). The relative roles of regulatory sequence versus exon-intron structure changes in the acquisition of novel function by human paralogs remains to be determined. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1827-3) contains supplementary material, which is available to authorized users

Transcriptional responses of Biomphalaria pfeifferi and Schistosoma mansoni following exposure to niclosamide, with evidence for a synergistic effect on snails following exposure to both stressors.

BackgroundSchistosomiasis is one of the world's most common NTDs. Successful control operations often target snail vectors with the molluscicide niclosamide. Little is known about how niclosamide affects snails, including for Biomphalaria pfeifferi, the most important vector for Schistosoma mansoni in Africa. We used Illumina technology to explore how field-derived B. pfeifferi, either uninfected or harboring cercariae-producing S. mansoni sporocysts, respond to a sublethal treatment of niclosamide. This study afforded the opportunity to determine if snails respond differently to biotic or abiotic stressors, and if they reserve unique responses for when presented with both stressors in combination. We also examined how sporocysts respond when their snail host is treated with niclosamide.Principal findingsCercariae-producing sporocysts within snails treated with niclosamide express ~68% of the genes in the S. mansoni genome, as compared to 66% expressed by intramolluscan stages of S. mansoni in snails not treated with niclosamide. Niclosamide does not disable sporocysts nor does it seem to provoke from them distinctive responses associated with detoxifying a xenobiotic. For uninfected B. pfeifferi, niclosamide treatment alone increases expression of several features not up-regulated in infected snails including particular cytochrome p450s and heat shock proteins, glutathione-S-transferases, antimicrobial factors like LBP/BPI and protease inhibitors, and also provokes strong down regulation of proteases. Exposure of infected snails to niclosamide resulted in numerous up-regulated responses associated with apoptosis along with down-regulated ribosomal and defense functions, indicative of a distinctive, compromised state not achieved with either stimulus alone.Conclusions/significanceThis study helps define the transcriptomic responses of an important and under-studied schistosome vector to S. mansoni sporocysts, to niclosamide, and to both in combination. It suggests the response of S. mansoni sporocysts to niclosamide is minimal and not reflective of a distinct repertoire of genes to handle xenobiotics while in the snail host. It also offers new insights for how niclosamide affects snails

The in vivo transcriptome of Schistosoma mansoni in the prominent vector species Biomphalaria pfeifferi with supporting observations from Biomphalaria glabrata.

BackgroundThe full scope of the genes expressed by schistosomes during intramolluscan development has yet to be characterized. Understanding the gene products deployed by larval schistosomes in their snail hosts will provide insights into their establishment, maintenance, asexual reproduction, ability to castrate their hosts, and their prolific production of human-infective cercariae. Using the Illumina platform, the intramolluscan transcriptome of Schistosoma mansoni was investigated in field-derived specimens of the prominent vector species Biomphalaria pfeifferi at 1 and 3 days post infection (d) and from snails shedding cercariae. These S. mansoni samples were derived from the same snails used in our complementary B. pfeifferi transcriptomic study. We supplemented this view with microarray analyses of S. mansoni from B. glabrata at 2d, 4d, 8d, 16d, and 32d to highlight robust features of S. mansoni transcription, even when a different technique and vector species was used.Principal findingsTranscripts representing at least 7,740 (66%) of known S. mansoni genes were expressed during intramolluscan development, with the greatest number expressed in snails shedding cercariae. Many transcripts were constitutively expressed throughout development featuring membrane transporters, and metabolic enzymes involved in protein and nucleic acid synthesis and cell division. Several proteases and protease inhibitors were expressed at all stages, including some proteases usually associated with cercariae. Transcripts associated with G-protein coupled receptors, germ cell perpetuation, and stress responses and defense were well represented. We noted transcripts homologous to planarian anti-bacterial factors, several neural development or neuropeptide transcripts including neuropeptide Y, and receptors that may be associated with schistosome germinal cell maintenance that could also impact host reproduction. In at least one snail the presence of larvae of another digenean species (an amphistome) was associated with repressed S. mansoni transcriptional activity.Conclusions/significanceThis in vivo study, emphasizing field-derived snails and schistosomes, but supplemented with observations from a lab model, provides a distinct view from previous studies of development of cultured intramolluscan stages from lab-maintained organisms. We found many highly represented transcripts with suspected or unknown functions, with connection to intramolluscan development yet to be elucidated

Salmonid alphavirus infection causes skin dysbiosis in Atlantic salmon (Salmo salar L.) post-smolts

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Additional file 1: Table S1. of Early evolutionary history and genomic features of gene duplicates in the human genome

Evolutionary and genomic features of 184 gene duplicates with low synonymous divergence in the human genome. (PDF 262 kb