5,951 research outputs found
The Alternative Choice of Constitutive Exons throughout Evolution
Alternative cassette exons are known to originate from two processes
exonization of intronic sequences and exon shuffling. Herein, we suggest an
additional mechanism by which constitutively spliced exons become alternative
cassette exons during evolution. We compiled a dataset of orthologous exons
from human and mouse that are constitutively spliced in one species but
alternatively spliced in the other. Examination of these exons suggests that
the common ancestors were constitutively spliced. We show that relaxation of
the 59 splice site during evolution is one of the molecular mechanisms by which
exons shift from constitutive to alternative splicing. This shift is associated
with the fixation of exonic splicing regulatory sequences (ESRs) that are
essential for exon definition and control the inclusion level only after the
transition to alternative splicing. The effect of each ESR on splicing and the
combinatorial effects between two ESRs are conserved from fish to human. Our
results uncover an evolutionary pathway that increases transcriptome diversity
by shifting exons from constitutive to alternative splicin
Predominant contribution of cis-regulatory divergence in the evolution of mouse alternative splicing
Divergence of alternative splicing represents one of the major driving forces to shape phenotypic diversity during evolution. However, the extent to which these divergences could be explained by the evolving cis-regulatory versus trans-acting factors remains unresolved. To globally investigate the relative contributions of the two factors for the first time in mammals, we measured splicing difference between C57BL/6J and SPRET/EiJ mouse strains and allele-specific splicing pattern in their F1 hybrid. Out of 11,818 alternative splicing events expressed in the cultured fibroblast cells, we identified 796 with significant difference between the parental strains. After integrating allele-specific data from F1 hybrid, we demonstrated that these events could be predominately attributed to cis-regulatory variants, including those residing at and beyond canonical splicing sites. Contrary to previous observations in Drosophila, such predominant contribution was consistently observed across different types of alternative splicing. Further analysis of liver tissues from the same mouse strains and reanalysis of published datasets on other strains showed similar trends, implying in general the predominant contribution of cis-regulatory changes in the evolution of mouse alternative splicing
Width of Gene Expression Profile Drives Alternative Splicing
Alternative splicing generates an enormous amount of functional and proteomic diversity in metazoan organisms. This process is probably central to the macromolecular and cellular complexity of higher eukaryotes. While most studies have focused on the molecular mechanism triggering and controlling alternative splicing, as well as on its incidence in different species, its maintenance and evolution within populations has been little investigated. Here, we propose to address these questions by comparing the structural characteristics as well as the functional and transcriptional profiles of genes with monomorphic or polymorphic splicing, referred to as MS and PS genes, respectively. We find that MS and PS genes differ particularly in the number of tissues and cell types where they are expressed.We find a striking deficit of PS genes on the sex chromosomes, particularly on the Y chromosome where it is shown not to be due to the observed lower breadth of expression of genes on that chromosome. The development of a simple model of evolution of cis-regulated alternative splicing leads to predictions in agreement with these observations. It further predicts the conditions for the emergence and the maintenance of cis-regulated alternative splicing, which are both favored by the tissue specific expression of splicing variants. We finally propose that the width of the gene expression profile is an essential factor for the acquisition of new transcript isoforms that could later be maintained by a new form of balancing selection
Comparative analysis of transposed element insertion within human and mouse genomes reveals Alu's unique role in shaping the human transcriptome
Background: Transposed elements (TEs) have a substantial impact on mammalian
evolution and are involved in numerous genetic diseases. We compared the impact
of TEs on the human transcriptome and the mouse transcriptome. Results: We
compiled a dataset of all TEs in the human and mouse genomes, identifying
3,932,058 and 3,122,416 TEs, respectively. We than extracted TEs located within
human and mouse genes and, surprisingly, we found that 60% of TEs in both human
and mouse are located in intronic sequences, even though introns comprise only
24% of the human genome. All TE families in both human and mouse can exonize.
TE families that are shared between human and mouse exhibit the same percentage
of TE exonization in the two species, but the exonization level of Alu, a
primatespecific retroelement, is significantly greater than that of other TEs
within the human genome, leading to a higher level of TE exonization in human
than in mouse (1,824 exons compared with 506 exons, respectively). We detected
a primate-specific mechanism for intron gain, in which Alu insertion into an
exon creates a new intron located in the 3' untranslated region (termed
'intronization'). Finally, the insertion of TEs into the first and last exons
of a gene is more frequent in human than in mouse, leading to longer exons in
human. Conclusion: Our findings reveal many effects of TEs on these two
transcriptomes. These effects are substantially greater in human than in mouse,
which is due to the presence of Alu elements in human
H-DBAS: human-transcriptome database for alternative splicing: update 2010
H-DBAS (http://h-invitational.jp/h-dbas/) is a specialized database for human alternative splicing (AS) based on H-Invitational full-length cDNAs. In this update, for better annotations of AS events, we correlated RNA-Seq tag information to the AS exons and splice junctions. We generated a total of 148 376 598 RNA-Seq tags from RNAs extracted from cytoplasmic, nuclear and polysome fractions. Analysis of the RNA-Seq tags allowed us to identify 90 900 exons that are very likely to be used for protein synthesis. On the other hand, 254 AS junctions of human RefSeq transcripts are unique to nuclear RNA and may not have any translational consequences. We also present a new comparative genomics viewer so that users can empirically understand the evolutionary turnover of AS. With the unique experimental data closely connected with intensively curated cDNA information, H-DBAS provides a unique platform for the analysis of complex AS
Recommended from our members
The how and why of lncRNA function: An innate immune perspective.
Next-generation sequencing has provided a more complete picture of the composition of the human transcriptome indicating that much of the "blueprint" is a vastness of poorly understood non-protein-coding transcripts. This includes a newly identified class of genes called long noncoding RNAs (lncRNAs). The lack of sequence conservation for lncRNAs across species meant that their biological importance was initially met with some skepticism. LncRNAs mediate their functions through interactions with proteins, RNA, DNA, or a combination of these. Their functions can often be dictated by their localization, sequence, and/or secondary structure. Here we provide a review of the approaches typically adopted to study the complexity of these genes with an emphasis on recent discoveries within the innate immune field. Finally, we discuss the challenges, as well as the emergence of new technologies that will continue to move this field forward and provide greater insight into the biological importance of this class of genes. This article is part of a Special Issue entitled: ncRNA in control of gene expression edited by Kotb Abdelmohsen
Characteristics of transposable element exonization within human and mouse
Insertion of transposed elements within mammalian genes is thought to be an
important contributor to mammalian evolution and speciation. Insertion of
transposed elements into introns can lead to their activation as alternatively
spliced cassette exons, an event called exonization. Elucidation of the
evolutionary constraints that have shaped fixation of transposed elements
within human and mouse protein coding genes and subsequent exonization is
important for understanding of how the exonization process has affected
transcriptome and proteome complexities. Here we show that exonization of
transposed elements is biased towards the beginning of the coding sequence in
both human and mouse genes. Analysis of single nucleotide polymorphisms (SNPs)
revealed that exonization of transposed elements can be population-specific,
implying that exonizations may enhance divergence and lead to speciation. SNP
density analysis revealed differences between Alu and other transposed
elements. Finally, we identified cases of primate-specific Alu elements that
depend on RNA editing for their exonization. These results shed light on TE
fixation and the exonization process within human and mouse genes.Comment: 11 pages, 4 figure
- …