ALTERNATIVE TRANSCRIPTION AND SPLICING OF DUPLICATED mitf GENES IN THE FISH MEDAKA

Abstract

ALTERNATIVE TRANSCRIPTION (AT) AND ALTERNATIVE SPLICING (AS) REPRESENT A HALLMARK OF EUKARYOTIC EVOLUTION. THIS THESIS WORK FOCUSED ON AT AND AS BY USING MICROPHTHALMIA-ASSOCIATED TRANSCRIPTION FACTOR (MITF) AS A MODEL GENE. THE FISH MEDAKA HAS TWO MITF GENES, MITF1 AND MITF2, ARISEN FROM GENE DUPLICATION. MITF1 PRODUCED 5 AND 3 TRANSCRIPT VARIANTS VIA AT AND AS, RESPECTIVELY. THESE VARIANTS EXHIBITED DIFFERENTIAL EXPRESSION. ISOFORMS PREDICTED FROM THESE MITF1 VARIANTS DIFFERED DRAMATICALLY IN ACTIVATING TARGET GENE EXPRESSION. INTRIGUINGLY, THESE MITF1 ISOFORMS POSSESS CONSIDERABLE DIFFERENCES IN INDUCING THE EXPRESSION OF MULTIPLE CELL LINEAGE MARKER GENES. INTERESTINGLY, MITF2 HAS A SINGLE PROMOTER AND THUS LACKS AT BUT IS ABLE TO PRODUCE 2 AS VARIANTS. THUS, MEDAKA MITF1 AND MITF2 SHOW A CONSIDERABLE DIFFERENCE IN THE RETENTION AND LOSS OF AT AND AS DURING THEIR EVOLUTION. THIS FINDING SHEDS NEW LIGHTS ON DIFFERENTIAL EVOLUTION AFTER GENE DUPLICATION THROUGH AT AND AS FOR INCREASI