Serna, A. | bioRxiv Science

bioRxiv2021

Telomere transcription in MLL-rearranged acute leukemia: increased levels of TERRA associate with lymphoid lineage and are independent of telomere length and ploidy

Telomere transcription into telomeric repeat-containing RNA (TERRA) is an integral component of all aspects of chromosome end protection consisting of telomerase- or recombination-dependent telomere elongation, telomere capping, and preservation of (sub)telomeric heterochromatin structure. The chromatin modifier and transcriptional regulator MLL associates with telomeres and regulates TERRA transcription in telomere length homeostasis and response to telomere dysfunction. MLL fusion proteins (MLL-FPs), the product of MLL rearrangements in leukemia, are also associated with telomeric chromatin. However, an effect on telomere transcription in MLL-rearranged (MLL-r) leukemia has not yet been evaluated. Here, we show increased UUAGGG repeat-containing RNA levels in MLL-r acute lymphoblastic leukemia (ALL) when compared to myeloid and non-MLL-r ALL leukemia. MLL rearrangements do not affect telomere length and increased levels of UUAGGG repeatcontaining RNA correlate with mean telomere length and reflect increased levels of TERRA. Also, increased TERRA levels in MLL-r ALL occur in the presence of telomerase activity and are independent of ploidy, an underestimated source of variation on the overall transcriptome size in a cell. This MLL rearrangement-dependent and lymphoid lineage-associated increase in levels of TERRA supports a sustained telomere transcription by MLL-FPs that correlates with marked genomic stability previously reported in pediatric MLL-r ALL.

cancer biology↗

bioRxiv2020

Hundreds of nuclear and plastid loci yield insights into orchid relationships

Premise of the studyEvolutionary relationships in the species-rich Orchidaceae have historically relied on organellar DNA sequences and limited taxon sampling. Previous studies provided a robust plastid-maternal phylogenetic framework, from which multiple hypotheses on the drivers of orchid diversification have been derived. However, the extent to which the maternal evolutionary history of orchids is congruent with that of the nuclear genome has remained uninvestigated. MethodsWe inferred phylogenetic relationships from 294 low-copy nuclear genes sequenced/obtained using the Angiosperms353 universal probe set from 75 species representing 69 genera, 16 tribes and 24 subtribes. To test for topological incongruence between nuclear and plastid genomes, we constructed a tree from 78 plastid genes, representing 117 genera, 18 tribes and 28 subtribes and compared them using a co-phylogenetic approach. The phylogenetic informativeness and support of the Angiosperms353 loci were compared with those of the 78 plastid genes. Key ResultsPhylogenetic inferences of nuclear datasets produced highly congruent and robustly supported orchid relationships. Comparisons of nuclear gene trees and plastid gene trees using the latest co-phylogenetic tools revealed strongly supported phylogenetic incongruence in both shallow and deep time. Phylogenetic informativeness analyses showed that the Angiosperms353 genes were in general more informative than most plastid genes. ConclusionsOur study provides the first robust nuclear phylogenomic framework for Orchidaceae plus an assessment of intragenomic nuclear discordance, plastid-nuclear tree incongruence, and phylogenetic informativeness across the family. Our results also demonstrate what has long been known but rarely documented: nuclear and plastid phylogenetic trees are not fully congruent and therefore should not be considered interchangeable.

evolutionary biology↗