9.7 KiB
Further development on FTAG Finder, a pipeline to identify Gene Families and Tandemly Arrayed Genes
| key | abbreviation | full form |
|---|---|---|
| TAG | TAG | Tandemly Arrayed Gene |
| FTAG | FTAG | Families and Tandemly Arrayed Gene |
| WGD | WGD | Whole Genome Duplication |
| MCL | MCL | Markov Clustering |
Duplicate genes is an important component of genomes. They have a particular role in genome evolution, allowing species to explore new gene functionality offering a pool of usable genes to build on. TODO:
keywords: duplicate genes, tandemly arrayed genes, pipeline
Context
It is estimated that between 46% and 65.5% of human genes could be considered as duplicate genes [cite:@correaTransposableElementEnvironment2021]. Duplicate genes offers a pool of genetic material available for further experimentation during species evolution.
Duplication mechanisms
Multiple mechanisms may lead to gene duplication. We review them in this section.
Segment duplication
Retroduplication
Retrotransposons, or RNA transposons are one type of transposable elements. Retrotransposons share similar structure and mechanism with retroviruses. They may replicate in the genome through a mechanism known as "copy-and-paste". These transposons are typically composed of a reverse transcriptase gene. This enzyme may proceed in the reverse transcription of an mRNA transcript into DNA sequence which can then be inserted elsewhere in the genome. More generally, retroduplication refers to the duplication of a region of a chromosome through reverse transcription or a RNA transcript.
Transduplication
DNA transposons are another type of transposable element whose transposition mechanism can also lead to gene duplication. This type of transposable element moves in the genome through a mechanisms known as "cut-and-paste". A typical DNA transposon contains a transposase gene. This enzyme recognize two sites surrounding the donnor transposon sequence in the chromosome resulting in a DNA cleavage and excision of the transposon. The transposase can then insert the transposon in a new place of the genome. Similarly to retrotransposon, if a gene was present between the two cleavage sites of the donnor transposon, it may move with the transposed sequence.
Tandem Duplication
Polyploidisation and Whole Genome Duplication
In an event of whole genome duplication, the entire set of genes present on the chromosomes is duplicated. Whole genome duplication is more frequent in plants. A striking example is probably the Triticum genus (wheat) in which some species (such as T. aestivum) are hexaploid, due to hybridisation events [cite:@golovninaMolecularPhylogenyGenus2007].
We distinguish two kinds of polyploidisation, based on the origin of the duplicate genome:
- Allopolyploidisation occurs when the supplementary chromosomes comes from an other species. This is the case for Triticum aestivum hybridisation.
- Autopolyploidisation consist in the hybridisation of the genome within the same species.
Whole genome duplication can occur thanks to polyspermy or in case of a non-reduced gamete, for instance.
Unequal crossing-over
A crossing-over may occur during cell division. A fragment of chromosome is exchanged between two chromatids of a pair of chromosome. If the cleavage of the two chromatids occured at different positions on both chromosomes, the shared fragments may have different lengths. When the repair of missing fragment is performed, the resulting chromosome will incorporate a duplicate region of the chromosome, leading to a potential duplication for genes present in this region, as represented in figure fig:gene-duplication-mechanisms. This mechanism leads to the duplication of the whole set of genes present in the inserted fragment. An array of genes is duplicated after the original array and are thus called Tandemly Arrayed Genes.
Role of duplicate genes in genome evolution
In his book Evolution by Gene Duplication, Susumu Ohno proposed that gene duplication plays a major role in species evolution [cite:@ohnoEvolutionGeneDuplication1970].
Methods to identify duplicate genes
Lallemand et al. review the different methods used to detect duplicate genes. These methods are dependant on the type of duplicate genes they target [cite:@lallemandOverviewDuplicatedGene2020].
FTAG Finder
Developped in the LaMME laboratory, this pipeline targets the detection of gene families and tandemly arrayed genes from a given species' proteome [cite:@bouillonFTAGFinderOutil].
Estimation of homology links between genes
This steps consists in establishing a relation between each genes in a genome.
In this step, the typical tool involved is BLAST (Basic Local Alignment Search Tool) [cite:@altschulBasicLocalAlignment1990] run on the whole proteome.
Several BLAST metrics can be used as an homology measure, such as bitscore, identity percentage, E-value or variations on those. The metrics choice may have an impact on the results of graph clustering in the following step [cite:@gibbonsEvaluationBLASTbasedEdgeweighting2015].
Identification of gene families
Based on the homology links between each pair of genes, we construct a weighted undirected graph whose vertices corresponds to genes and edges to homology links. Then, a graph clustering algorithm is applied on this graph in order to infer the gene families.
The team chosed to propose three clustering algorithms: Single linkage, Markov Clustering or Walktrap.
Objectives
Extend the existing Galaxy pipeline
Galaxy is a web-based platform for performing accessible data analysis pipeline, first designed for use in genomic data analysis [cite:@goecksGalaxyComprehensiveApproach2010].
Last year, Séanna Charles, worked on the Galaxy's version of the gls:FTAG Finder pipeline during her M1 internship [cite:@charlesFinalisationPipelineFTAG2023]. I will continue this work.
Port FTAG Finder pipeline on a workflow manager
Another objective of my internship will be to port FTAG Finder on a workflow manager better suited to larger and more reproducible analysis.
We will have to make a choice for the tool we will use. The two main options are Snakemake and Nextflow. Snakemake is a python powered workflow manager based on rules à la GNU Make [cite:@kosterSnakemakeScalableBioinformatics2012]. Nextflow, is a groovy powered workflow manager, which rely on data flows [cite:@ditommasoNextflowEnablesReproducible2017]. Both are widely used in the bioinformatics community, and their use have been on the rise since they came out in 2012 and 2016 respectively [cite:@djaffardjyDevelopingReusingBioinformatics2023].
These tools ease the deployment of large scale data analysis workflow with reproducible output.