FUNCTIONARCHITECTURE · Functional implications of the remarkable conservation of eukaryotic gene architecture
FP7 — People (Marie Curie Actions)
- Duration
- 2010-01-01 → 2013-12-31
- EU contribution
- €100,000
- Participants
- 1
- Scheme
- MC-IRG
Lines connect the coordinator with its partners.
Results in brief
Functional implications of the remarkable conservation of eukaryotic gene architecture
Reconstructions of intron evolution in the past several years have reached a consensus, viewing spliceosomal introns as neutral or slightly deleterious elements that rapidly spread throughout eukaryotic genomes during the very early days of eukaryogenesis. Consequently, most eukaryotic lineages harbored numerous introns. These introns, being non-coding segments at a close proximity to the coding exons, form a major evolutionary playground. Intronic mutations can accumulate at almost neutral rate, and just by chance some would be advantageous and would acquire function. Today, after way more than a billion years of eukaryotic evolution, many introns fulfill important cellular functions and are essential to the organism (we published a review about it, see [Igor B. Rogozin, Liran Carmel, Miklos Csuros and Eugene V. Koonin, Origin and evolution of spliceosomal introns, Biology Direct 7 (2012) 11]). However, since intron roles are regulatory and diverse, and sometimes even independent on their sequence, there is no good way to tell which intron is functional. The fundamental hypothesis underlying this project is that functionally important introns should be characterized by distinct evolutionary trajectories. For example, we them to display decreases rates of loss, to be present in more closely related species, etc. Evolution of introns can be traced back in time by analyzing the conservation of their position with respect to the exonic mRNA sequence, or the intron positional conservation. The project is designed to prove the link between intron positional conservation and intron function, and to identify the evolutionary trends that are unique to functional introns. Specifically, we have suggested three specific aims. Aim 1: Building a gene architecture database, that will keep architectonic properties of genes in many eukaryotes. Aim 2: Testing the hypothesis that intron positional conservation is indicative of functionality. Aim 3: Characterizing the positional distribution of introns with high level of positional conservation. Our work during the project duration (2009-2013) culminated, as we hoped, in the first characterization of functional introns, and a classifier that reliably discriminates functional introns from non-functional ones [Michal Chorev and Liran Carmel, Computational identification of functional introns: high positional conservation of introns that harbor RNA genes, Nucleic Acids Research 41 (2013) 5604-5613]. This is the first work to suggest a way to predict whether a particular intron is functional or not, and was therefore selected by the Nucleic Acids Research editorial board as a featured article (to 5% of articles in the journal). See an example of several properties that characterize functional introns in Figure 1 below.
Data: CORDIS, © European Union
Project objective
One of the fundamental principles in comparative genomics is that evolutionary conservation implies functional importance. This principle has been used extensively in the life sciences, as a tool to detect biological functionality. In the vast majority of studies, evolutionary conservation has been sought in three biological “entities”: sequence (actual nucleotide or amino-acid sequences, as well as sequence properties like codon usage bias, GC content, and amino-acid bias); structure (like RNA, DNA and protein secondary and tertiary structures); and genome architecture (like synteny, gene order, relative gene orientation). These strategies have worked very well, but evidence is rapidly accumulating that there is a lot of “function without detectable conservation”. Many factors can potentially contribute to such “undetected functionality”, such as functions that do not depend on sequence or structure (for instance, nonsense mediated decay is affected by the mere location of the introns), functions that depend on very short and redundant sequence motifs, co-evolution of factor and target, and migration of functional sequences along the chromosome. We suggest a novel strategy to identify parts of these “undetected functions”. We study how to quantify the conservation in a fourth type of biological “entity”, that we dub gene architecture, and which is derived from the exon-intron structure of the gene. To this end, we are building a eukaryotic gene architecture database, and developing an algorithm to quantitatively evaluate the level of architectonic conservation in the different regions of the gene. Preliminary analysis reveals that conservation of gene architecture is plentiful, and in many cases it can be detected over very long evolutionary times (more than a billion years). This allows us to identify genic elements, mostly introns and splice junctions, which are likely to be of functional importance.
Original text from CORDIS.
Participants
- THE HEBREW UNIVERSITY OF JERUSALEM · JerusalemCoordinatorIsrael
Links
Data: CORDIS, © European Union