House mouse chromosome with homogenously staining regions (HSR) in meiosis

RFBR 19-04-00021

Сells should undergo meiosis for gametes to be produced. In meiosis each chromosome must pair with its homolog. But what if one chromosome would be 1.5 times longer than a homolog? What if it has an inverted region? How would a cell carry out meiosis with such unusual chromosomes?

We answer these questions in our research on the house mouse chromosome with homogenously staining regions (HSR). In fact, we already have results to share with you!

The HSR chromosome is longer, than its homolog — to understand the possibility of their pairing we tracked changes during meiosis. We observed fully synapsed linear homomorphic bivalents 1 both in hetero- and homozygotes, using fluorescent in situ hybridization with HSR specific DNA probe. Studying different meiosis stages, we noticed bilateral synaptic adjustment (not so unique phenomenon): HSR chromosome becomes shorter to match the normal homolog and its homolog becomes longer. But changes in HSR chromosome after synapsis are thrilling: it is again (as before meiosis) significantly longer, and the elongation of its separate regions is uneven with both HSR regions lengthen more than euchromatin parts. The mechanisms of such reversable synaptic adjustment are unknown.

Is recombination in aberrant region of HSR chromosome possible in homo- or heterozygotes? Using immunolocalization we detected peaks of MLH1 foci (marking mature recombination nodules) at distal and proximal euchromatic regions both in the homo- and heterozygotes. In addition, 10% of MLH1 foci in the homozygotes locate in the euchromatic region between two HSRs. To our surprise, we detected one cell with MLH1 focus in the inverted region! We are cautious about that result, because it can be an artifact either of immunolabelling or FISH. We also observed unexpected MLH1 foci in the HSRs themselves, both in homo- and heterozygotes — this could lead to differences of HSR size, as field studies have shown.

The homozygotes for HSR chromosome survive poorly. With that in mind, if recombination in aberrant region of heterozygotes is so rare, we can consider that the chromosome with HSR must be exposed to the Möller ratchet. Thus, it should be an excellent model for assessing the accumulation rate and composition of the genetic load. That is the question we addressing right now, analyzing the genome of the HSR homozygous mouse.

Stay tuned!

Publications

Torgunakov, N.Y., Kizilova, E.A., Karamysheva, T.V., Malinovskaya, L.P., Bikchurina, T.I., Borodin, P.M. Homogeneously Staining Regions (HSR) in Chromosome 1 of the House Mouse: Synapsis and Recombination at Meiosis. Cytogenet. Genome Res., 2021, 161:14–22 , doi.org/10.1159/000513266.

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