Ranajit Das

Defense Date

6-23-2014

Graduation Date

Fall 2014

Availability

Immediate Access

Submission Type

dissertation

Degree Name

PhD

Department

Biological Sciences

Committee Chair

Michael I Jensen-Seaman

Committee Member

Brady Porter

Committee Member

David Lampe

Committee Member

Nathan Clark

Keywords

Eastern Lowland Gorilla, In vitro Luciferase Assay, Promoter-Silencer Interaction, Seminal plasma proteins, TMRCA, Unique hominoid miRNAs

Abstract

The complete mtDNA of one eastern gorilla was sequenced to provide the most accurate date for the mitochondrial divergence of gorillas. The most recent common ancestor of eastern lowland and western lowland gorillas existed about 1.9 million years ago, slightly more recent than that of chimpanzee and bonobo. This study also depicts that the eastern and western gorillas show species level genetic divergence.

Hominoid mating systems differ tremendously. The level of sperm competition varies according to the mating system, which presumably imposes unique selective pressures on the seminal proteins of each species. Cartilage acidic protein 1 (CRTAC1) was identified in our lab as the protein with the largest difference in abundance between human and chimpanzee, being found at 142-fold higher in chimpanzee. The coding region of CRTAC1 is extremely conserved with signature of strong purifying selection. Paradoxically, CRTAC1 `promoter' from human drives transcription significantly greater than chimpanzee, with or without androgen stimulation. Analyzing H3K27Ac data, a ~2.2kb region was identified as a possible additional cis-regulatory element. The cis-regulatory region behaved like a silencer and aided in strong transcriptional repression in humans. Although its underlying basis remains elusive, it can be speculated that the differential expression of CRTAC1 between human and chimpanzee seminal plasma results from tissue specific over/under expression of this gene.

The unique gains and losses of miRNAs within hominoids have remained understudied. The overall goal of this project was to identify the uniquely gained and lost miRNAs and their targets within hominoids. I found 14 miRNAs uniquely gained in humans. Maximum uniquely gained and lost miRNAs were found to be brain specific. The targets of uniquely gained miRNAs in human are also associated with brain-associated functions. Older miRNAs were found to be more conserved compared to the newer miRNAs gained <15 Mya.

Format

PDF

Language

English

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