Comparison of orthologs across multiple species by various strategies

Liu, Hui

Permalink

https://hdl.handle.net/2142/49436 Copy

Description

Title

Comparison of orthologs across multiple species by various strategies

Author(s)

Liu, Hui

Issue Date

2014-05-30T16:44:00Z

Director of Research (if dissertation) or Advisor (if thesis)

Jakobsson, Eric

Doctoral Committee Chair(s)

Jakobsson, Eric

Committee Member(s)

• Robinson, Gene E.
• Sinha, Saurabh
• Ma, Jian

Department of Study

School of Molecular & Cell Bio

Discipline

Biophysics & Computnl Biology

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• orthology
• alignment
• zinc finger
• honeybee
• social-behavior

Abstract

Thanks to the improvement of genome sequencing technology, abundant multi-species genomic data now became available and comparative genomics continues to be a fast prospering filed of biological research. Through the comparison of genomes of different organisms, we can understand what, at the molecular level, distinguishes different life forms from each other. It shed light on revealing the evolution of biology. And it also helps to refine the annotations and functions of individual genomes. For example, through comparisons across mammalian genomes, we can give an estimate of the conserved set of genes across mammals and correspondingly, find the species-specific sets of genes or functions. However, comparative genomics can be feasible only if a meaningful classification of genes exists. A natural way to do so is to delineate sets of orthologous genes. However, debates exist about the appropriate way to define orthologs. It is originally defined as genes in different species which derive from speciation events. But such definition is not sufficient to derive orthologous genes due to the complexity of evolutionary events such as gene duplication and gene loss. While it is possible to correctly figure out all the evolutionary events with the true phylogenetic tree, the true phylogenetic tree itself is impractical to be inferred. Furthermore, evolutionary orthology does not necessarily have a strict correspondence to function similarity. Kruppel type zinc finger genes are important transcription factor families in eukaryotic species. Important as it is, the evolution of this zinc finger family is not completely clear yet. For example, the vertebrate roots of the KRAB-ZNF family in particular and of polydactyl ZNF genes in general, remain somewhat mysterious. In addition, due to its repeating gene structure and the fact that they often reside as clusters, these genes can be difficult to model correctly with common gene-finding tools. Furthermore, due to the repeating gene structures, conventional tools like BLAST lack the necessary sensitivity to successfully define orthologous relationships. This research presents a novel and species-specific way of defining orthology for zinc finger genes-‘fingerprint’ alignment, hundreds of lineage-specific genes in each species and also hundreds of orthologous groups are found. Most groups of orthologs displayed some degree of fingerprint divergence between species. Focusing on the dynamic KRAB-ZNF subfamily, only three genes conserved between mammals and nonmammalian groups are found. These three genes, members of an ancient familial cluster, encode an unusual KRAB domain that functions as a transcriptional activator. Evolutionary analysis confirms the ancient provenance of this activating KRAB and reveals the independent expansion of KRAB-ZNFs in every vertebrate lineage. Most human ZNF genes, from the most deeply conserved to the primate-specific genes, are highly expressed in immune and reproductive tissues, indicating that they have been enlisted to regulate evolutionarily divergent biological traits. Notably, the honeybee has been successfully used as a model to study social-behavior. The honeybee has highly-socialized colony and exhibits varieties of social behaviors such as foraging. Simultaneously, it is relatively simple and easy for honeybee to be manipulated comparing to other social animals. However, it is still unclear about the evolutionary relationship between honeybee and other social animals like human. Specifically, is there a conserved common genetic basis for social behavior between honey bee and human? Based on conventional ortholog data defined by whole-sequence comparison, ortholog distribution patterns are compared for sets of aggression-related honey bee genes. We found that for one particular stimulus, response to alarm pheromone, the set of honey bee genes differentially expressed in the brain contains disproportionately large numbers of genes also found in mammals, including humans. Functionally, a large number of the human counterparts of these genes are important for regulating protein folding, a process whose misregulation is prominently implicated in human neurodegenerative disease. Moreover, the human counterparts are also predicted to be co-regulated similarly to the bee genes that respond to alarm pheromone, even though alarm pheromone is a highly species-specific signal. These results suggest surprisingly strong similarities in socially responsive genetic circuits common to honey bees and mammals.

Graduation Semester

2014-05

Permalink

http://hdl.handle.net/2142/49436

Copyright and License Information

Copyright 2014 Hui Liu

Owning Collections