Banca de QUALIFICAÇÃO: CLOVIS FERREIRA DOS REIS

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
DISCENTE : CLOVIS FERREIRA DOS REIS
DATA : 27/06/2018
HORA: 11:00
LOCAL: IMD
TÍTULO:

Synonymous mutations and neutral evolution in bacteria

&

Analysis of Transcriptional Data of Human Neural Progenitor Cells Exposed to Lead

 

PALAVRAS-CHAVES:

Molecular Evolution. Codon Bias. Long term evolution experiment. Adaptiveness index. Positive selection. Synonymous mutation.

Lead (Pb) exposure. Transcriptogramer. RNA-Seq. Transcriptome analysis. Time series. Network inference. Data integration. Network visualization.

PÁGINAS: 58
GRANDE ÁREA: Ciências Biológicas
ÁREA: Biologia Geral
RESUMO:

Part I

The study of molecular evolution allows inferring how genetic mutations work  over time. Long Term Evolution Experiments (LTEE) brings to us new way to corroborate theories wich was based only limited and restricted experiments. This work  aims  to verify the influence of synonymous  mutations (Syn)  over prokaryotes  fitness,  its  correlation  with  genome  codon  bias  and  develop  a method to measure this correlation. Later we try to correlate observed mutation under a systemic approach where it was compared to the genome plasticity index and expression data. Therefore we use data of an LTEE involving 50,000 generations of E. coli REL606 where 12 bacteria populations had two clones sequenced  over 11 distinct generations.  For  each group population/age, all observed  Single  Nucleotide  Variants  (SNV)  was  classified  as  Syn  or Nonsynonymous (Non) and recorded. Was create one genome per group with all observed mutations to act as a reference for next generation and the codon adaptation index (w) was calculated.  We propose a w variation index (∆w), based on the ratio of mutation's w over reference's w, to quantify the influence of codon bias over Syn preservation. The analysis of ∆w values could allow inferring if a hypothetical slowing down on the translation ratio of mutated mRNA have any impact on selection, creating a selective pressure over Syn. We created a random and selection free comparison base using a 20,000 rounds Monte  Carlo  simulation  (MC)  where  aleatory  mutations  are  inserted  into reference genome, classified and it ∆w was calculated. In the end, we couldn't confirm the initial hypothesis, and an unequivocal relation between mutations and neutral selection couldn't be established.

Part II

Implications of lead poisoning are important for human health. Lead virtually affects all human systems, especially nervous system. Health concern about lead poisoning  relies  in  its  irreversible  detriment  to  neurodevelopment,  affecting normal memory consolidation and learning processes in children. Lead has been reported  to  interact  with  many  cellular  components,  such  as  ion  binding proteins,  transduction  signaling  proteins,  membrane  ion  channels,  and transcription factors. Here, we applied the transcriptogramer R/Bioconductor package  pipeline  to  evaluate  the  transcriptional  profile  of  human  neural progenitor cells (NPCs) treated with lead acetate 30μM in a time-dependent manner. Transcriptogramer is a non-supervised system biology-based method designed to identify functionally associated gene groups differentially expressed in  case-control  designed  experiments.  The  pipeline  was  able  to  identify differentially expressed clusters in early time of lead treatment. Those clusters increased  in  number  of  genes  as  times  goes  on.  Enrichment  analysis  of differentially  expressed  clusters  revealed  the  modification  in  glycosylation pathways, lipid biosynthesis, G-protein pathways, cytoskeleton organization, ion channels metabolism, and cellular division process in early time of treatment. In late time of treatment, nearby genes were incorporated on each cluster and new GO terms have been identified, such as zinc and calcium related terms. The transcriptogramer  pipeline  was  able  to  identify  several  genetic  systems transcriptionally  altered  in  lead-treated  NPCs,  including  pathways  welldescribed as affected by lead. In conclusion, lead induces huge transcriptional modifications in NPCs which can be related to system damage and/or system adaptation in response to lead.

MEMBROS DA BANCA:
Presidente - 1507794 - RODRIGO JULIANI SIQUEIRA DALMOLIN
Interno - 1939184 - SANDRO JOSE DE SOUZA