LCHES research

The Cambridge-Leverhulme Initiative in Post-Genomics Research	Human Evolution & Development: Evolution, post-genomics and contextual biology
Principal Investigator:	Dr. Robert A. Foley
Co-Investigators:	Prof. P. Bateson, Prof. B. Keverne, Dr. M. Mirazón Lahr
Collaborators:	Dr. J. Stock, Dr. Nick Mundy, Dr. L. Vinicius Castilho, Dr. James Curley
Funding:	The Leverhulme Trust

A collaborative research initiative between LCHES and the Department of Zoology, Cambridge

One of the most powerful ideas in the Darwinian revolution was that biological diversity was 'context dependent'. Patterns of biological function, adaptation and distribution in time and space depended upon seeing organisms in the context of their environment. The technical demands of molecular biology, which culminated in the HGP, often led to a dilution of this perspective. In effect post-genomics can be seen as the second Darwinian revolution, returning to contextual biology with a far greater understanding of the complexity of the environment in which organisms, including humans, develop and evolve. This environment ranges from the genome itself to the cellular conditions of development to the ecological and cultural settings of individuals and populations. This initiative represents a strategy for the development of contextual biology within a post-genomic framework.

Members of LCHES are carrying out three projects within the Cambridge-Leverhulme Initiative in Post-Genomic Research:
Project 1: Adaptive Evolutionary Heritage - Heterochony and allometry in the evolution of human ontogeny
Project 2: Adaptive Environmental Mechanisms - Ecological patterning of human growth & development
Project 3: The Evolutionary Context of Human Post-Genomic Research

Professor Pat Bateson and Professor Barry Keverne, from the Sub-Department of Animal Behaviour, Department of Zoology , Cambridge, co-ordinate two further projects: "Development and the mammalian evolutionary heritage: genomic imprinting" and "Alternative Modes of Development: Plasticity and Epigenesis"

A STRATEGY FOR INTEGRATIVE POST-GENOMIC RESEARCH
A number of pivotal moments have occurred in the history of science when biologists have radically changed their view of organisms. The acceptance of Darwin's theory of evolution was clearly one such, as was the discovery of the structure of the genetic code of inheritance. While the first of these led to biologists looking at what had previously been considered separate problems in an integrated way, the second could be said to have led to a separation between whole organism research on the one hand, and a more reductionist approach to biology on the other - the search for the fundamental descriptor of any living system at the molecular level. The publication of the genetic sequence for humans, the fruit of the Human Genome Project, can be thought of as the end of this phase.

Post-genomics research represents a new pivotal moment in the biological sciences. Its foundations lie in bringing together molecular and whole organism aspects of biological systems, to understand how these have evolved and function, comparable to the way in which Darwinism brought together such diverse branches of the embryonic life sciences as genetics, physiology and development, palaeontology, biogeography, and ecology. In this post-genomics phase, human biological research has to be re-oriented to address the question of how the knowledge of our genetic code can be transformed into a baseline for a new integrated biology of humans.

Across biology as a whole, we can recognise two distinct long-term post-genomic strategies.

Functional Post-Genomics Research is the unravelling of the translation of the DNA sequence into genes and their products, and from these the identification of the entire human genomic function. We foresee the greatest impact of this research strategy on the medical sciences, and its forum within both research institutes like the Sanger Centre and private biomedical enterprises.
Integrated Post-Genomics Research is the advancement of our knowledge of the development of humans, its regulation, function, variability and evolution. Human development is the outcome of complex gene-environment interactions, and its link to the genetic code can only be made once the mechanisms behind variability of expression are understood. Both strategies of post-genomics research have to develop in tandem and feed each other's progress in order to achieve the biological synthesis that should emerge from knowing the human genetic sequence.

The Cambridge-Leverhulme Initiative aims at developing and promoting this second strategy of Integrated Post-Genomics Research. It proposes to bring together anthropological and zoological research that directly addresses the evolutionary biology of human development under a single post-genomics programme, and thus foster this integrative phase of the biological sciences.

The Cambridge-Leverhulme Initiative
The genetic code, embedded in the human genome, has been revealed by the HGP. If one asked why biological science was not transformed overnight by the publication of the human genome, the answer would lie in the fact that having the sequence does not tell us how genes build organisms. Understanding the ways in which information, embedded in the genome, interacts with internal and external forces to become the characteristics of the whole individual is a key priority for post-genomics research. By pursuing the second post-genomics strategy, the Cambridge-Leverhulme Initiative in Post-Genomics will focus on the interaction of these genetic instructions within the genome and the cellular environment, within the ecological and cultural contexts of the growing individual, and within the historical and demographic background of the populations to whom the individuals belong. The overall aim of this strategy is to understand the mechanisms that generate variation in humans, as well as the ontogenetic and phylogenetic components of this variation upon which Darwinian and other evolutionary mechanisms operate.

Beyond the intrinsic interest on human biology, we believe that humans offer a unique opportunity to study the mechanisms and processes that shape the phenotype in a population level context. In this conceptual framework, humans offer a particularly fascinating challenge for a number of related reasons:

Human development and growth is particularly prolonged, with a very large proportion taking place post-natally, and therefore in the context of a more complex environment than most mammals.

The evolution of the human brain has resulted, to some extent, in an emancipation of behaviour patterns from the deterministic influence of hormones, and therefore a greater detachment of development from the direct influence of genes.

Humans live in complex social systems, and so the environmental component related to intra-specific interactions is particularly high.

Humans live in physical environments in which there is a very high degree of environmental buffering, and thus elements of the environment, which play a major role in the development of other species, are strongly mediated in humans by cultural factors.

Across the globe humans live in remarkably different environmental conditions (social, cultural, economic and ecological), and thus the scope for variation influencing growth and development at this level is very high.

The extremely rich cultural and biological record of human evolution open new avenues of enquiry into how and to what extent this unique pattern and context of growth and development is a product of our particular evolutionary history, over the long term (mammalian and primate heritage), medium term (unique human universals), and short term (generating differences among humans).

The Cambridge-Leverhulme Initiative offers the context in which one of the two main long-term strategies of human post-genomics research - Integrated Post-Genomics, should be pursued. It focuses on evolution and development in humans, comprising general evolutionary biology, anthropology, developmental biology, behaviour, ecology, evolutionary molecular genetics, and functional genomic interactions. It is organized around five themes. Each of these has at their core different means of scientific enquiry, from subject to technical implementation. Together they explore the complexity of the factors affecting gene expression and the importance of looking at the whole organism in an evolutionary context, and serve as foundations for future expansion into baseline and applied post-genomics research. These are:

Development and the mammalian evolutionary heritage: genomic imprinting.

Adaptive evolutionary heritage - heterochrony and allometry in the evolution of human ontogeny

Alternative modes of development: plasticity and epigenesis,

Adaptive environmental mechanisms - ecological patterning of human growth and development

The evolutionary history and context of human development.

The evolutionary history and context of humans attempts to build an integrated framework for human evolution, one in which the major changes in hominin biological, demographical and social environments are ecologically contextualised, as well as their spatial and temporal diversity in behavioural and morphological patterns. This framework will then serve as the basis for exploring the evolutionary context of changes in human growth and development.

Genomic imprinting addresses the factors influencing gene expression at the genomic level, with particular focus on brain development.

The evolution of human growth explores the mechanisms by which ontogeny influences human morphology, focusing on the evolutionary processes that regulate the timing and growth of different parts of the body.

Plasticity and epigenesis investigates the role of intra-uterine and postnatal environments on the phenotype/genotype interaction at different phases of the life cycle.

Finally, the ecology of human development explores the environmental, behavioural and cultural factors underlying the evolution of diverse patterns of growth in human populations.

Although these components have their own research aims and strategies, all five research areas are linked together by a concern with the unique features of humans and the extent to which behavioural and ecological factors influence development.