Much of what makes us human is written in our genome the rest results from how our genes interact with the environment
Changes in gene activity underlie much of the phenotypic differences observed between species. We study how gene activity patterns change during evolution and disease states and what factors modulate these changes on a genome wide scale. To address these topics we use an in silico approach using bioinformatics tools to process large expression (Microarrays/ESTs/RNA-Seq), functional and genomic datasets.
In a broad sense I am interested in how genes and genomes evolve through time and how these changes an help us better understand the function and interaction between genes during normal development/adult life and disease states. To address these issues I use bioinformatics tools to analyse large scale genomic and functional data for a number of mainly mammalian species.
My current research addresses the following main questions: 1) How alternative splicing has evolved through time and what is the role of alternative splicing in normal and disease states? 2) What are the genomic bases of the evolution of complex phenotypes and behaviour in mammalian and avian systems and other eukaryotic taxa? 3) What factors account for gene and genome evolution in plants and drosophila? Details of some of past and current research questions follow:
Are highly expressed genes at all adapted for cost-efficient and accurate expression?
We have found that highly active genes have shorter introns, higher codon usage bias and encode shorter proteins with higher frequencies of less complex amino acids. In addition, we have found that rates of protein evolution are strongly influenced by intron splicing requirements, a fact that partially explains why broadly expressed genes evolve slowly. These findings provide a snapshot into the broad relationships at the genomic scale between genes and their activity profiles which, contrary to prior expectations given the small population size of mammalian species, are consistent with selection on reducing costs and maximisation of accuracy of protein synthesis.
But are the properties of highly expressed genes the result of ongoing selective pressures within mammalian lineages? Current projects address this questions using a comparative genomics approach in mammalian genomes
Are expression patterns and alternative splicing related to genomic context?
Surprisingly, as gene order was thought to be mostly random, we found that housekeeping genes cluster in gene dense GC rich regions of the genome. Continuing work on these questions addresses the reasons behind the relationship between genome organization and expression profiles. In particular I am studying the possible functional relevance of gene sorting according to expression profiles in the genome by using a comparative analysis approach in yeast genomes. I am also studying the effects of genome rearrangements on gene expression profiles and the role of alternative splicing.
What variables modulate patterns of gene activity divergence at a genomic scale?
Contrary to recent work based single-genome analyses supporting a prominent role of the SINE family of Alu repeats in primate transcriptome evolution, using a comparative analysis we have found that these repeats do not in fact have any significant impact on genome evolution. Current work investigates whether there is any evidence of an involvement of Alu sequences in developmental regulatory control and also looking for short term effects of Alu insertion on primates.
How gene activity evolves through time in response to changes in the environment
Are changes in gene activity patterns the result of selective pressures or do they evolve neutrally as much of the sites on the DNA molecules? We use a transcriptomics comparative approach to evaluate the changes in gene expression in response to environmental changes.
If you are interested in collaborating with us or would like to join the lab please get in touch!
Evolutionary Functional Genomics Lab