Evolution of Homeobox Genes and Mammalian Embryo Development - WCUB, ENWW

Lead Research Organisation: University of Oxford
Department Name: Interdisciplinary Bioscience DTP

Abstract

Changes in the regulation of embryonic development are major players in the evolution of complex organisms. The homeobox gene superclass encode DNA-binding proteins, many of which possess an important function in embryogenesis. We are looking at homeobox genes with specific expression in the early embryo of eutherian mammals; mammals that develop a placenta and an extended pregnancy resulting in live birth. These genes, however, are highly variable among different species of eutherian mammal, some so divergent they are no longer recognisable as related genes, and some lost from the genome all together. This project will investigate the function and phylogenetic distribution of these embryonic genes (ETCHbox genes) in mice and other rodents. In mice, the subset of ETCHbox genes retained in the genome is unusually reduced and remaining genes have expanded compared to other eutherians. As these genes have only very recently evolved, understanding their function and the mechanisms behind their variability will provide insight on how evolutionarily new genes are co-opted into new functions, as well as potentially increasing understanding on the mechanisms behind the emergence of eutherian mammals.

BBSRC Priority Areas:

Data driven biology: This project has a substantial bioinformatic component. Analysing large data sets after sequencing analysis and working with genome data to define the phylogenetic distribution of genes results in this study being largely driven by the acquisition and existence of sequencing data.

The replacement, refinement, and reduction in research using animals (3Rs): The methodologies that are described here aim to do functional work on embryonic genes with minimal in vivo animal work. Experiments will be carried out in established cell lines for the most part which reduces any potential ethical issues with this study.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011224/1 01/10/2015 31/03/2024
1810161 Studentship BB/M011224/1 01/10/2015 31/12/2019
 
Description We are interested in the evolution and function of the earliest stages of mammalian development. We have discovered that, although some genes show marked differences in gene sequence and number between mouse and human genomes, there is some overlap in their function.

Additionally we have analysed the evolutionary history of these genes and identified subfunctionalisation in the placental mammal lineage, followed by what we think is specialisation of their function
Exploitation Route Our results inform about the earliest stages of mouse development and draw comparisons between mouse and human embryogenesis. We show that gene family evolution can be very dynamic and supply an instance of where intense gene content evolution may contribute to phenotypic evolution.
Sectors Other

URL https://evodevojournal.biomedcentral.com/articles/10.1186/s13227-018-0091-4