Although
DNA gain and loss in human occurred mostly in different regions, they both tended to impact on the same biological processes, while in mouse DNA loss was enriched for developmental genes and DNA gain did not associate with any particular biological process.
To understand the evolutionary impacts and trajectories of
DNA gain and loss dynamics we analysed their genomic distributions in the context of various genomic features and biological processes.
Therefore, the role of genome structure on widespread
DNA gain and loss and its subsequent impact on lineage - specific species evolution remains unknown.
To understand the relationship between both the spatial and temporal dynamics of
DNA gain and loss, we analysed the genomic distribution of
DNA gain and loss events that occurred between each divergence event.
We also investigated various groups of transposons whose genomic distributions have been previously characterised and used to investigate genome - wide
DNA gain and loss rates.
Using our identified
DNA gain and loss events it is possible to characterise genome - wide patterns of
DNA gain and loss and to begin to determine how DNA turnover may impact on mammalian genome evolution.
This makes it possible to compare them to a wide variety of outgroup species and detect genomic features that associate with
DNA gain and loss.
For our analysis, we detected
DNA gain and loss events using two distinct, yet complementary, methods from which we characterised
DNA gain and loss hotspots.
Importantly, our understanding of
DNA gain and loss stems from genome - wide estimates rather than detection of individual events.
Citation: Buckley RM, Kortschak RD, Adelson DL (2018) Divergent genome evolution caused by regional variation in
DNA gain and loss between human and mouse.
In addition, we also measured how gene in
DNA gain and loss hotspots associate with gene regulatory blocks (GRBs), genomic regions preserved between mammals and birds that are enriched for highly conserved elements [72].
Collectively, these results demonstrate that it is possible to identify locations for the majority of
DNA gain and loss events since human and mouse divergence.
However in contrast to hg19, older mm10
DNA gain and loss events show strong negative associations with each other (Fig 8).
Consistent between both methods is size distribution difference between
DNA gain and loss.
To better characterise the molecular drivers and evolutionary impacts of
DNA gain and loss, we calculated lineage - specific gain and loss rates across the human and mouse genomes.
Thus, regional / species specific variation in
DNA gain and loss are primarily driven by clade specific / recent transposons interacting with open chromatin either in the male germ line, female germ line or early embryo.
This is consistent with a model in which
DNA gain and loss results in turnover or «churning» in regulatory element dense regions of open chromatin, where interruption of regulatory elements is selected against.
Our results showed that both hg19 and mm10 underwent similar temporal patterns of
DNA gain and loss.
It indicates that the recent transposon method is a reasonably effective method in identifying
DNA gain and loss in species where it is difficult to detect ancestral elements.
First, we identified
DNA gain and loss hotspots using the hotspot identification procedure described in the methods section.
Next, the genomic distribution for each set of time - specific
DNA gain and loss hotspots were then compared by performing Fisher's exact test based on their overlap, hotspot overlaps were considered significant if their FDR was < 0.05.
Bins with less than 150 kb of DNA not belonging to RBH nets were removed and our tallies were normalised to reflect
DNA gain and loss amounts per 200 kb.
To better understand the spatio - temporal dynamics of
DNA gain and loss, we dated individual DNA gain or loss events using a series of ingroup species that each mark specific divergence events between either human or mouse (Methods).
Fourth, the observed autosomal divergence of gain and loss hotspot patterns in proximity to genes supports a model in which developmental / regulatory mechanisms (based on GO term results) are robust to large amounts of transposon driven
DNA gain and loss.
Focusing on the distribution of
DNA gains and losses, relationships to important structural features and potential impact on biological processes, we found that in autosomes,
DNA gains and losses both followed separate lineage - specific accumulation patterns.
Our results revealed that
DNA gains and losses occur in different regions across autosomes, while DNA gains from both species are particularly enriched on the X chromosome where they overlap.
This creates a synthetic genome consisting of
DNA gains and losses that occurred across both the reference and query lineages.
This suggests that for the most part the accumulation of
DNA gains and losses have had little impact on phenotypic change.
Interestingly, Human
DNA gains and losses and mouse DNA losses all occurred near genes involved in fundamental cellular / metabolic processes.
Because DNA loss is caused by repair of DNA Double Stranded Breaks (DSB)[81], this means that L1 ORF2p activity can both cause
DNA gains and losses as a cause of DSB.
First, hot spots for
DNA gains and losses occur in different compartments; loss hot spots in open chromatin / regulatory regions and gain hot spots in heterochromatin.
Collectively, our results show that the regional distribution of
DNA gains and losses over time have been highly dynamic and most likely the result of complex interactions between genome organisation, genome biology and transposon activity.
Not exact matches
«Our study shows that epigenetic drift, which is characterized by
gains and losses in
DNA methylation in the genome over time, occurs more rapidly in mice than in monkeys
and more rapidly in monkeys than in humans,» explains Jean - Pierre Issa, MD, Director of the Fels Institute for Cancer Research at LKSOM,
and senior investigator on the new study.
DNA gain events generally associate with L1 accumulation
and DNA loss occurs in regions associated with biological activity such as transcription
and regulation.
These non-aligning reference sequences are absent from the query
and are either the result of
DNA gain in the reference or
DNA loss in the query.
However, the high level of consistency for both methods in identifying hg19
DNA gain and mm10
DNA loss where there is good support for outgroup species is highly encouraging.
To determine whether or not increased
DNA gain or
loss likely had an evolutionary impact we compared human
and mouse gene expression divergence.
They performed testing for IDH1 R132H
and ATRX by immunohistochemistry (IHC); 1p / 19q deletion, 7p
gain,
and 10q
loss by
DNA array;
and IDH 1
and 2
and H3.3 K27M by sequencing.
The resulting
DNA copy number variation
and patterns of chromosome
loss and gain are tumor - type specific, suggesting differential selective pressures on the two tumor cell types.
For this study, researchers conducted genome - wide sampling of methylation, gene expression
and DNA structural abnormalities, including the
gain or
loss of
DNA.
Through
DNA testing we analyze genetic markers known to impact weight
gain or
loss, metabolism, exercise,
and energy use within the human body.