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DNA recombination

Biological background

Ciliates exhibit nuclear dimorphism through the presence of somatic mancronuclei (MAC) and germline micronuclei (MIC).

The MAC controls metabolism, and works as a template for genes required for asexual growth. Its DNA is the one actively expressed and effectively results in the phenotype of the organism.

The MIC has reproductive functions, produces meiotic products during sexual reproduction (conjugation). Its DNA is passed during this phase.

The rearrangement process

In some ciliates - e.g. the species Oxytricha trifallax (genus Oxytricha, class Spirotrichea) - the MAC DNA is derived from the MIC DNA by extensive DNA recombination.

This process consists in:

  • The MAC begins a copy of the MIC DNA. The chromosomes are fragmented and amplified The result of this process is the precursor. ~90% of the complexity is lost.
    • Fragmentation
    • Amplification
  • From the precursor the final MAC DNA is produced through these further operations:
    • Elimination
    • Inversion
    • Telomere Addition
    • Gene Scrambling / Unscrambling

The extent and the nature of these operations varies among ciliate species.

The precursor DNA pieces are called Macronuclear-Destined Sequences (MDSs). Precursor's MDSs are interrupted/separated by Internally-Eliminated Sequences (IESs): they mostly fall between genes in the Tetrahymena but in Oxytricha and Paramecium they interrupt them.

MDSs overlap slightly in the MAC (pointers).

Some complex IESs in Oxytricha can even contain MDSs for other genes or entire genes themselves (AV\footnotemark: how to handle overlap?).

Some MDSs rearranges during the MAC development (AV\footnotemark: is this a different phase?).

This entire - error correcting - mechanism is guided by small RNAs and epigenetic chromatin marks (AV\footnotemark: The resulting map is definitely correlated with this. What is the role of understanding this mechanism in our work? )

Instance

Input

  • MIC (or precursor?) and MAC (AV\footnotemark: should the sequences be already annotated with the MDSs, IESs and pointers?)

Respectively the input and the product genomes (Input and Output of the described DNA rearrangement process in the named species of Ciliates).

Admissible Solution

A rearrangement map: a set of disjoint substrings representing the building blocks (MDSs, IESs, pointers), eventual operations they will go through the process (scrambling, inversion/orientation, ..) and their "destination" on the MAC final produced genome.

An algorithm g should then be able to build the product genome having the input and the computed rearrangement map (and viceversa).

f(MIC, MAC) = Map
g(MIC, Map) = MAC
g'(MAC, Map) = MIC

AV\footnotemark: Should the precursor building process be considered? i.e. the first input could be the MIC or the precursor:

MIC is fragmented and amplified to produce the precursor, should we accept the former, and include these operations in the solution (maybe in phases) or the latter, and accept directly the precursor as input?