Ciliate - DNA Rearrangements (gene Scrambling)

DNA Rearrangements (gene Scrambling)

Ciliates contain two types of nuclei: the somatic "macronucleus" and the germline "micronucleus". Only the DNA in the micronucleus is passed on during sexual reproduction (conjugation). On the other hand, only the DNA in the macronucleus is actively expressed and results in the phenotype of the organism. Macronuclear DNA is derived from micronuclear DNA by amazingly extensive DNA rearrangement and amplification.

The macronucleus begins as a copy of the micronucleus. The micronuclear chromosomes are fragmented into many smaller pieces and amplified to give many copies. The resulting macronuclear chromosomes often contain only a single gene. In Tetrahymena, the micronucleus has 10 chromosomes (5 per haploid genome), while the macronucleus has over 20,000 chromosomes.

In addition, the micronuclear genes are interrupted by numerous "Internal Eliminated Sequences" (IESs). During development of the macronucleus, IESs are deleted and the remaining gene segments, Macronuclear Destined Sequences (MDSs), are spliced together to give the operational gene. Tetrahymena has about 6000 IESs and about 15% of micronuclear DNA is eliminated during this process. The process is guided by small RNAs and epigenetic chromatin marks.

In spirotrich ciliates (such as Oxytricha), the process is even more complex due to "gene scrambling": the MDSs in the micronucleus are often in different order and orientation from that in the macronuclear gene, and so in addition to deletion, DNA inversion and translocation are required for "unscrambling". This process is guided by long RNAs derived from the parental macronucleus. More than 95% of micronuclear DNA is eliminated during spirotrich macronuclear development.