I am interested in the causes and effects of mRNA editing in kinetoplastid mitochondria. Kinetoplastid mitochondria have a remarkably elaborate system of uridine insertion and deletion editing which in some cases changes more residues than are originally transcribed. This creates an additional task for ribosomes, which need to distinguish between unedited and improperly edited mRNA, which they should not translate, and properly edited mRNA, which they should. I am testing the hypothesis that kinetoplasts exploit the large size of their mitochondria, over 5 µm long, to spatially or stucturally segregate edited from unedited mRNAs. At present I am identifying membrane associations of ribosomes, edited, and unedited mRNA; I predict greater membrane association for ribosomes and edited mRNA than unedited mRNA.
I am also interested in the evolutionary mechanisms that caused and maintains the editing process. Editing requires a collection of several dozen classes to several hundred of vertically transmitted plasmid-like minicircles. Each class has multiple copies and the total number of minicircles per cell is in the thousands. Since the number in each class can vary by errors in replication rates and partitioning amongst offspring, maintaining functioning sets of minicircles is unlikely by chance over evolutionary time. A currently popular theory holds that number of minicircles varies randomly over time due to neutral partitioning errors and that complete functioning sets are maintained by loss of lineages in which an essential class has been loss. The distribution of mincircle copy numbers fits this model but initial estimates of changes in each copy number over time do not. I plan to investigate for selective effects on minicircle copy number by maintaining multiple clonal lineages over time and observing changes in minicircle copy number. The neutral model predicts that the variance in minicircle copy number over time should be propotional to the square root of the copy number; selection theory broadly predict greater changes to copy number in populous classes.
An intriguing side note to selection on minicircle copy number (if it occurs) is that it would approximate Darwin's original model of evolution much more closely than standard Mendelian genetics. Darwin originally proposed that novel variants were created in the process of reproduction while Mendelian genetic proposes the reproduction mostly just shuffles exiting variants around. Kinetoplasts reproduce, so Mendelian segregation does not happen; yet minicircle copy number appear to change each generation, conforming to the Darwinian model. Kinetoplasts mitochondria may model not neodarwinian evolution but Darwinian evolution sensu stricto and, if so, would be the first such case.
PUBLICATIONS:
Conn RL; Muschter R; Adams CS; Esch V. 1996. International Registry Results for an Interstitial Laser BPH Treatment Device. SPIE Proceedings, Volume 2671, pp. 316-320.
Litvack R, Eigler N; Margolis J; Rothbaum D; Bresnahan JF; Holmes D; Untereker W; Leon M; Kent K; Prichard A; King S; Ghazzal Z; Cummins F; Krauthamer D; Palacios I; Block P; Hartzler G; O'Neill W; Cowley M; Roubin F; Klein L; Frankel PS; Adams C; Goldenberg T; Laudenslager J; Grundfest WS; Forrester JS. 1994. Percutaneous Excimer Laser Coronary Angioplasty: Results in the First Consecutive 3,000 Patients. Journal of the American College of Cardiology, Volume 23(2) pp. 323-9.