What is the problem/issue being addressed?
A whole genome is a complete sequence of the DNA that each cell in a living organism contains. With the undertaking of the human genome project, we entered a new era of studying DNA where we can obtain complete sequences of chromosomes; the building blocks of genomes. Over evolutionary time, chromosomes diverge in their organization and content as species evolve and diversify. Understanding exactly how these changes occurred is a major goal in biology. Since the human genome project, DNA sequencing technology has evolved vastly substantially increasing the number of genomes across different species., yet with more genomes comes greater analytical challenges. Despite constant methodological advances in genomics, it is still difficult and time consuming to compare the genome structure of different species and identify how physical characteristics of organisms are influenced by changes in chromosome structure.
During this project, we focussed on specific genomic sequences that are highly conserved in vertebrate animals. These ~2000 bits of vertebrate genomes have remained the same despite 300+ million years of evolution. They are called ‘Ultraconserved Elements’ or UCEs. Each UCE has a different nucleotide sequence, yet individual UCEs are near identical across more than 33,000 species of tetrapods (a group that contains birds, reptiles, amphibians, and mammals). Scientists are not completely sure why UCEs have remained so conserved over evolutionary time, but prominent hypotheses include that they are important for developmental regulation and/or the stability of genome structure. In the ULTRAMOD project, we leverage the conserved nature of UCEs to compare different chromosomes across species with the goal of yielding new insights into how chromosome structure differs across species.
Why is it important for society?
Genomic data are imperative to human society, from tracking strains of disease-causing organisms to identifying how prone someone is to a particular condition, understanding underlying drivers of evolutionary change, adaptation and more. Genome data are also used to cultivate and breed plants and animals as well as make them more resistant to disease and environmental stress. The ability to compare and analyse whole genome data is limited by computational resources. Methods such as ours that do not require access to high performance computing will play a key role in making genomics more accessible to everyone, notwithstanding political borders and power differences.
What are the overall objectives?
Based on the availability of genomes, we expanded the scope of ULTRAMOD, which was originally restricted to lizards and snakes, to include all tetrapod animals. We sought to answer several key questions about UCEs in different species. Initially we asked three questions. First, how are UCEs distributed across the genome? Second, do all chromosomes have UCEs? Third, how can we compare the position of UCEs on many different species at the same time? Because specific UCEs are linked to genes that play a key role in limb development, we were also interested in their link to limb loss which is observed in some tetrapod groups like snakes and lizards. To achieve these objectives, we developed a method to landmark UCEs on the chromosomes of different species and are also sequencing a high-quality genome from an endemic limbless lizard from Sri Lanka.
