Quantitative regulation of alternative splicing in evolution and development

Abstract

Alternative splicing (AS) is a widespread mechanism with an important role in increasing transcriptome and proteome diversity by generating multiple different products from the same gene. Evolutionary studies of AS have focused primarily on the conservation of alternatively spliced sequences or of the AS pattern of those sequences itself. Less is known about the evolution of the regulation of AS, but several studies, working from different perspectives, have recently made significant progress. Here, we categorize the different levels of AS evolution, and summarize the studies on evolution of AS regulation, which point to a high level of evolutionary conservation of the regulation of AS events conserved between related species. This suggests that the quantitative regulation of AS is an intrinsic part of AS function. We discuss the potential role of changes in developmental regulation of AS as an additional layer in complex gene regulatory networks and in the emergence of genetic novelties.

Distinct and redundant expression and transcriptional diversity of MEIS gene paralogs during chicken development

“…A, atrium; ba, branchial arches; bd, bile duct; da, dorsal aorta; dp, dorsal pancreas; du, duodenum; oe, oesophagus; Hyp, hypothalamus; inf, infundibulum; l, lens; lv, liver; lb, lung buds; Mes, mesencephalon; nr, neural retina; nt, notochord; ov, omphalomensenteric vena; of, optic furrow; pe, pigmented epithelium; ph, pharynx; PT, pretectum; p1b, prosomere 1 basal plate; rp, roof plate; sv, sinus venosus; SC, spinal cord; st, stomach; Th, thalamus; V, ventricle. Scale bar ¼ 300 mm in F. et al, 1997; Knoepfler et al, 1997;Shim et al, 2007;Yang et al, 2000) are conserved in chicken at both the genomic and splicing levels, and likely also at the regulation level (Irimia et al, 2009). Interestingly, the alternative region of exon11 in Meis2 seems to be present in the genomic sequence of exon11 of Meis1, although it could not be detected in any transcript, consistent with observations in other species (Maeda et al, 2001;Williams et al, 2005).…”

“…2). We find conservation at the genome level (i.e., exonic sequence and potential splice sites; Irimia et al, 2009) for both AS events in both chicken Meis genes. To assess the conservation of the AS, we designed a pair of primers for each region in both chicken paralogs (see the Experimental Procedures section) and performed reverse transcriptase-PCR (RT-PCRs) in different tissues and for a range of stages of development and diverse postnatal brain regions (Fig.…”

Alternative splicing and the evolution of phenotypic novelty

“…This predicts the rapid divergence of alternative splicing events between species, except if they are selectively constrained. Conserved patterns of differential exon usage, and in some cases, conserved expression profiles have been observed for a proportion of genes in species including nematodes [103] mammals [104,105] and grapevine cultivars [92] (see [106] for more examples). Conserved alternative splicing profiles have also been identified in a lineage-, species-and tissue-specific manner among vertebrates [107,108].…”

Interleukin-7 (IL-7) and IL-7 splice variants affect differentiation of human neural progenitor cells

“…Up to 75% of the human genome is currently estimated to be alternatively spliced. 12 Alternative splicing contributes to the evolution of protein diversity; [13][14][15] both microRNAs and alternative pre-mRNA splicing are implicated in the development of the neuronal system. Neuron-specific microRNA (miR)-124 contributes to progenitor cell differentiation and matures neurons by regulating a complex network of alternative splicing associated with neuronal development.…”