טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentHryshkevich Uladzislau
SubjectEvolutionary Genomics and Transcriptomics
DepartmentDepartment of Biology
Supervisor Professor Itai Yanai
Full Thesis textFull thesis text - English Version


Abstract

Precise execution of gene expression programs is controlled by the set of instructions encoded in the genome. The evolutionary changes to gene expression, therefore, could be in principle traced to the specific alterations in the genome sequence. However, while a lot of progress has been made in our understanding of gene expression evolution, much less is known about the genetic nature of such changes. The focus of my PhD thesis work is in uncovering the genomic consequence of gene expression evolution, and the effect that genomic constraints may impose on evolution. Here I present my research, organized in three separate chapters.

First, I report a periodic poly-thymine motif, which I term T-blocks, enriched in occurrences within core promoter forward strands in Caenorhabditis elegans. An increasing number of T-blocks on either strand is associated with increasing nucleosome eviction. Strikingly, only forward strand T-blocks are correlated with expression levels, whereby genes with ≥ 6 T-blocks have fivefold higher expression levels than genes with ≤ 3 T-blocks. I further demonstrate that differences in T-block numbers between strains predictably affect expression levels of orthologs. Collectively, these results suggest that core promoters may tune gene expression levels through the occurrences of T-blocks, independently of the spatio-temporal regulation mediated by the proximal promoter.

Next, I will demonstrate an existence of genomic constrain in genes propensity to form genotype-environment interactions. I analyze the transcriptomes of five C. elegans strains (genotype) cultivated in five growth conditions (environment), and find that highly regulated genes, as distinguished by intergenic lengths, motif concentration, and expression levels, are particularly biased toward genotype-environment interactions. Sequencing these strains reveals that genes with expression variation across genotypes are enriched for promoter single-nucleotide polymorphisms (SNPs), as expected. However, genes with genotype-environment interactions do not significantly differ from background in terms of their promoter SNPs. Collectively, these results indicate that the highly regulated nature of particular genes predispose them for exhibiting genotype-environment interaction as a consequence of changes to upstream regulators.

Finally, I show that previously observed inverse correlation between alternative splicing and gene duplication is a consequence of their mutual correlation with the gene length. I demonstrate that gene length is associated with both a gene’s family size and its number of encoded splice variants, accounting for a dominant portion of their relationship. Gene duplicates are shorter - due to partial duplications and increased survival of shorter duplications - but increase in length with time.