Date of Award

6-18-1982

Document Type

Open Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Abstract

The cloning of DNA fragments derived from the (beta)-like globin gene cluster of normal and (beta)('+)-thalassemic individuals is described. These and other cloned human DNA fragments are employed to define the strucure and transcription of a family of interspersed, repetitive RNA polymerase III transcription units in human DNA. These data allow unequivocal identification of these transcription units with the Alu family of interspersed, repetitive DNA sequences. Comparison of these sequences to those of other primate and rodent interspersed repeats reveals that the primate sequence resembles in many respects a dimer of the rodent sequence. This striking interordinal divergence stands in marked contrast to the strong intraordinal and intraspecies similarities characteristic of these interspersed repeats.Our observation of hydridization between the human Alu family sequence and the 7S RNA, a conserved, small cellular RNA species, prompted comparison of the two structures of the nucleotide sequence level. Along with other workers, we have noticed that a long internal stretch of 7S sequence information is absent from all Alu-like repeats examined.From this data, a model for the evolution of the rodent and primate Alu-like repeats from the 7S RNA is developed. This model postulates that aberrent replicational activities characteristic of certain viral RNA-directed-RNA and DNA polymerases were responsible for different rearrangements of 7S RNA sequences in rodents and primates. After fixation of one or a small number of these rearrangements by genomic integration, the model postulates their clonal amplification via the actions of RNA polymerase III, reverse transcriptase, and cellular DNA repair enzymes.This model adequately explains the known structural and transcriptional properties of the Alu-like interspersed repeats without recourse to assumptions of positive phenotypic benefit. In fact, the underrepresentation of these sequences in primate mRNA's, documented here, suggests that their amplification may have been phenotypically deleterious on many occasions. Thus, the Alu-like interspersed repeats may be classic examples of "selfish" DNA.

Comments

Title page incorrectly states date the dissertation was submitted. Per the author's copy and library stamping, the correct date is June 18, 1982.

Open Access

This Article is Open Access

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