Award details

Revealing the processes causes and correlates of molecular evolutionary rates of mammals

Reference	BB/D017750/1
Principal Investigator / Supervisor	Dr Andrew Rambaut
Co-Investigators / Co-Supervisors
Institution	University of Edinburgh
Department	Inst of Evolutionary Biology
Funding type	Research
Value (£)	213,288
Status	Completed
Type	Research Grant
Start date	01/10/2006
End date	30/09/2009
Duration	36 months

Abstract

The proposed research is a comprehensive investigation of the causes and consequences of variation in the rate of molecular evolution in mammals. The work stems from a recognition that multiple factors may influence the substitution rate in a particular gene in a particular lineage; these include properties of the gene which apply to all lineages, properties of the lineage applying to all genes in that lineage, and factors that apply solely to one gene in one lineage. The research aims to separate and quantify these components of rate variation, and to make progress towards identifying their causes. Then, the work aims to make practical use of the patterns found to develop new methods for molecular dating and phylogenetic estimation. Finally, these improved methods will be used to address controversies about the ordinal radiation of mammals. The research falls into four interlinked stages. Stage 1 is the development of a new analytical framework for partitioning variation in the rate of mammalian molecular evolution. The method will be implemented in a freely-available software package, and applied to large multi-species, multi-locus DNA datasets. Stage 2 aims to identify life-history and other correlates of the lineage component of molecular rate variation. Our method will account for correlations between life-history variables, and for phylogenetic non-independence. Stage 3 will test the hypothesis that significant gene-by-lineage interactions (equivalent to overdispersal of the substitution rate after correction for lineage effects), are due to adaptive evolution. Stage 4 will utilise results from the previous stages as prior knowledge in a Bayesian MCMC phylogenetics and dating package. The new methods will be then be used to estimate dates for the origin of the mammalian orders. In this way, a detailed study of recent mammalian molecular evolution will be used to improve inferences about the origin of their major groups.

Summary

The genomes of all organisms are directly comparable, because they are all made of DNA sequences with the same four letters, A, C, T and G. As genomes are copied from one generation to another, occasional mistakes are made, for example, a G might be added instead of a T. This mutation from G to T may be passed on from parent to offspring and become an inherited part of the genome of all their descendents. The more times DNA is copied, the more chance there is for mutations to accumulate. So the more distantly related organisms are, the more differences we expect to see between their genomes. This works on recent timescales (your genome will be more similar to your sister's, because you share a parent, than it is to your cousin's, with whom you share a grandparent) and on evolutionary timescales (the human genome is, on average, 98% similar to the chimp genome, but only 85% similar to the mouse genome). Therefore we can use the amount of differences between genomes to estimate evolutionary time. This technique, known as molecular dating, has revolutionised biology, providing a timescale for evolutionary events ranging from the origins of HIV to the beginnings of the animal kingdom. But the results have often been controversial. In particular, there is growing evidence that the rate of genomic change may not be the same in all species. For example, mammal species with short generation times (such as mice, which can reproduce every 3 months) copy their DNA more often than species with long generation times (such as elephants, which take ten years to reach reproductive age), so a mouse genome should accumulate more mutations per unit time than an elephant genome. So if we want to use DNA sequences to date evolutionary events, we have to allow for the fact that different lineages can have different rates of change. To do this, we need to develop a clearer understanding of how rates of molecular evolution vary between different genes, across the genome, and between species. This project will use mammals as a test case, because comparable gene sequences are available for a large number of mammal species, and there is a lot of information about mammalian characteristics (such as generation time), ecology, fossil record and evolutionary relationships. By using statistical techniques to compare the rate of change in different genes across different species, we hope to be able to discover whether a gene tends to evolve at the same rate in all species, or if a species has a characteristic rate of evolution across all of its genes. We will compare the rate of molecular evolution across species to see if any particular biological traits appear to explain the variation in rate (taking into account the fact that more closely related species are likely to have more similar characteristics). We will also develop methods for detecting the effects of natural selection in the evolution of genes in mammals. We will use this understanding of gene and lineage effects to develop better computational methods for analysing DNA sequences, combining fossil dates with data on mammalian characteristics, and allowing for variable rates of genomic evolution. We can use these new methods to test controversial theories about the origins of mammals. It has long been believed that modern mammals diversified only after the dinosaurs went extinct. Previous analyses of genetic data have suggested a radically different picture - that mammals diversified in the Cretaceous long before the dinosaur extinctions. But are these old molecular dates due to the fact that the early mammals were smaller, with much shorter generation times, so had faster rates of molecular evolution? We hope to make more reliable date estimates from molecular data to test these important hypotheses. More importantly, the methods we develop for this grant can be used for a much wider range of questions in biology, when sufficient data becomes available.

Committee	Closed Committee - Genes & Developmental Biology (GDB)
Research Topics	Technology and Methods Development
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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