Quantitative and evolutionary biology of alternative splicing: how changing the mix of alternative transcripts affects phenotypic plasticity and reaction norms

Abstract

Alternative splicing (AS) of pre-messenger RNA is a common phenomenon that creates different transcripts from a single gene, and these alternative transcripts affect phenotypes. The majority of AS research has examined tissue and developmental specificity of expression of particular AS transcripts, how this specificity affects cell function, and how aberrant AS is related to disease. Few studies have examined quantitative between-individual variation in AS within a cell or tissue type, or in relation to phenotypes, but the results are compelling: quantitative variation in AS affects plastic traits such as stress, anxiety, fear, egg production, muscle performance, energetics and plant growth. Genomic analyses of AS are also at a nascent stage, but have revealed a number of significant evolutionary patterns. Growing knowledge of upstream genes and kinases that regulate AS provides the as-yet little explored potential to examine how these genes and pathways respond to environmental and genotype variables. Research in this area can provide glimpses of a labyrinth of genetic architectures that have rarely been considered in evolutionary and organismal biology, or in quantitative genetics. The scarcity of contribution to knowledge about AS from these fields is illustrated by the fact that heritability of quantitative variation in AS has not yet been determined for any gene in any organism. New research tactics that incorporate quantitative analyses of AS will allow organismal and evolutionary biologists to attain a fuller mechanistic understanding of many of the traits they study, and may lead to more rapid discovery of functionally important polymorphisms.

Mammalian mRNA Splice-Isoform Selection Is Tightly Controlled

“…The scale in A-C is the percentage fraction of the shorter isoform relative to the total of both isoforms: [short isoform/(short isoform 1 long isoform)] 3 100. The numerical values for the population means and standard deviations are given in Table 2. control point for tissue-specific phenotype determination and homeostasis (Marden 2006). Four strategies may prove valuable in confirming this hypothesis in future experiments.…”

Differential Expression of Glycerol-3-Phosphate Dehydrogenase Isoforms in Flight Muscles of the Chagas Disease Vector Triatoma infestans (Hemiptera, Reduviidae)

“…27 In this regard, in previous studies in T. infestans, we demonstrated that the GPDH isoforms are not distributed equally in space or time. It was determined that expression is related to insect tissue or development stage and the pattern of expression differs between sexes.…”

Systematic evaluation of the effect of common SNPs on pre-mRNA splicing

“…There is a growing realization that splicing efficiency is a significant contributor to phenotypic variability (Marden, 2008), and the contribution of splicing to phenotype has become particularly apparent through its impact on modifying the severity of human disease (Nissim-Rafinia and Kerem, 2002) and its contribution to disease susceptibility (Wang and Cooper, 2007). Indeed, a key factor in the motivation for the present study was the recent positional cloning of the first sarcoidosis (a polygenic autoimmune disorder of the lungs (Valentonyte et al, 2005)) disease gene, namely BTNL2.…”