Distinct replication mechanisms leading to polyploidy. Jessica R. Von Stetina¹, Noa Sher¹, George Bell¹, Shinobu Matsuura², Katya Ravid², Terry L. Orr-Weaver¹. 1) Whitehead Inst, Dept. of Biol., MIT, Cambridge, MA; 2) Boston University Medical School, Boston MA.

   Polyploidy is fundamental for the terminal differentiation of many large or highly metabolic cells in both plants and animals. In Drosophila, most differentiated larval and adult tissues increase DNA content via the endo cycle, in which repeated rounds of DNA replication take place in the absence of cell division. Mammalian placental trophoblast giant cells (TGCs) also use endocycles to become polytene. In contrast, mammalian blood megakaryocytes (MKs) polyploidize via endomitosis, mitosis without nuclear division or cytokinesis. In Drosophila endocycles replication of the genome is not uniform; differential replication leads to under-replicated domains and amplified genes. We isolated TGCs and MKs from mice and performed array Comparative Genome Hybridization to test for differential replication. Replication of the euchromatin is uniform, in striking contrast to Drosophila tissues. Furthermore, quantitation of copy number of heterochromatic genomic regions in TGCs by qPCR revealed full replication of heterochromatin. Analysis of the transcriptome of TGCs and MKs shows profound differences in expression of cell cycle regulatory genes compared to Drosophila endocycling cells, highlighting distinct parameters for endoreplication between mice and flies.