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Genome Evolution in the Animal Kingdom

Final Report Summary - GENEVA (Genome Evolution in the Animal Kingdom)

The shape and form of each species is dependent on the process of embryonic development. If cells make different decisions in the embryo, then the adult will be different. Hence, the great diversity of animal life must be rooted in great diversity of embryos. But how does evolution change embryos? Evolution takes place through inherited changes to genes: mutations in DNA that become fixed in time. Of particular relevance must be mutations in genes such as homeobox genes which encode regulators of other genes in development. The goal of the ERC project ‘Genome Evolution in the Animal Kingdom’ was to investigate a special type of mutation – gene duplication – and how it affects these genes. Gene duplication can take place by two main routes – a single gene being accidentally copied along a chromosome to make two versions (tandem duplication), or an error in cell division whereby every chromosome and gene in the genome becomes doubled (whole genome duplication). We studied both mechanisms.
Whole genome duplication occurred twice in our history ~450 million years ago. We examined a set of three homeobox genes generated by these events. The three Cdx genes pose a conundrum because they are utilised at the same time and place as each other suggesting similar roles, but why would evolution keep all three genes for 450 million years if they did the same job? We reduced the function of each gene in turn in frog embryos and found that each regulated different genes. This showed that evolution can change gene function without changing expression. We also wanted to know how genes initially start to change, but for this question we needed to see genome duplication ‘in action’. After trying several approaches, we invented a new method of triangulating back in time. A genome duplication occurred in fish, around 350 million years ago, and thus by analysing genomes of fish that split in evolution just after this event we could infer what happened in the first few million years after a genome duplication. Surprisingly, we found that the duplicated genes do not necessarily start to change straight away, but instead recombination can keep them identical for many millions of years. This slows down sequence change and means genome duplication events can influence speciation and evolution over very long periods of time.
Tandem duplication affects just one gene at a time, but we found it is the most important route for generating ‘new’ types of genes in evolution. This is because after duplication one copy often changes little, while the second gene accumulates many mutations rapidly becoming a distinct type of gene. We discovered that the origin of animals, the origin of placental mammals, the evolution of molluscs, and the origin of advanced moths and butterflies, all experienced new genes arising by this route. Gene loss also occurs because the mutation process is dynamic, and we discovered tapeworms as the most extreme case of gene loss. We studied the moth and mammal examples in greater detail, finding that in each case tandem duplication generated new homeobox genes that were recruited for important new developmental roles. For example, in mammals we used ectopic gene expression in cell culture followed by RNA sequencing to reveal that the new homeobox genes prepare the early preimplantation embryo (8-cell to 16-cell) for the earliest cell decisions that must be made in development. Although this finding came from a research project focussed on evolution, the discovery has practical biomedical implications. In moths, the new genes most likely acquired roles in protecting the egg from desiccation on a leaf, influencing the evolution of 150,000 species. Finally, in comparing the genomes of many animal species, we found unexpected patterns in the distribution of mutations, which leads us to deduce the existence of mutation hotspots in genomes. This has implications for understanding the mode and tempo of evolution.