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The evolution of gene function
Since Darwin, the central task of evolutionary biology has been to provide
an historical explanation for biodiversity -- the great number of species
in nature, each with features so well adapted it to its environment. With
the rise of molecular biology, a new level of biodiversity has emerged
which demands an explanation -- the remarkable variety of genes in our
genomes, each with specialized and optimized for its functions within the
cell. We would like to understand the mechanisms and dynamics by which
genes and the proteins they code for evolved their diverse functions. We
employ a synthesis of evolutionary and phylogenetic techniques with
functional molecular biology and biochemistry. Our current model system is
a gene family of great biological and biomedical importance.
The Functional Synthesis in molecular biology and
evolution
We are interested in fascinating, unresolved
questions about the evolutionary processes, such as whether adaptation
proceeds by many small steps or a few large ones, whether interactions
among mutations limits the pathways and outcomes that evolution can
explore, whether the outcomes of evolution are deterministic or contingent
upon low-probability chance events, whether evolution is reversible, how
complexity evolves, and what the mechanisms are for the evolution of new
functions. All of these questions depend upon the map that relates
changes in gene sequence to changes in gene function and, ultimately, in
phenotype. They remain unresolved because evolutionary biologists have,
until recently, ignored the connection between genotype and phenotype by
treating genes as mere beans in a bag or long strings of letters. We are
advocates of the Functional
Synthesis in molecular biology and evolution -- a combination of
evolutionary approaches for reconstructing history with the experimental
strategies of molecular biology and biochemistry to rigorously test
hypotheses about the mechanisms of evolution.
Molecular evolution of hormones and their
receptors
How did hormones and their diverse functions in
humans and other animals evolve? We study the evolution of vertebrate
steroid hormones -- such as estrogen, testosterone, and the stress hormone
cortisol -- and the receptor proteins that mediate these hormones' effects
on the body's cells. Our goal is to reveal the specific molecular events
by which hormones and receptors diversified and evolved their specific
partnerships during the last 600 million years or so. By
combining techniques from statistical phylogenetics,
molecular endocrinology, ancestral gene resurrection, structural biology,
biophysics, and experimental evolution, we are characterizing receptor
biodiversity across the animal kingdom, testing hypotheses about the
functions of ancient proteins, and determining the specific mutations and
changes in protein structure by which new receptor functions evolved
hundreds of millions of years ago. Our goal is to offer a complete
mechanistic and historical explanation for a complex, tightly integrated
molecular system.
Phylogenetic techniques
We are also evaluating and developing new phylogenetic methods for
analyzing gene family evolution. We are particularly interested in
understanding how heterogeneity in the evolutionary process affects the
accuracy of current techniques, and in developing new methods that
perform better when sequences evolve differently among sites and
lineages.
Environmental health and policy
Many pesticides and industrial chemicals can cause severe effects on
reproduction, development, behavior, and immunity, because they mimic
or block the actions of our body's steroid hormones. I have long been
interested in how scientific knowledge can be used to support policies
that protect both natural systems and democratic principles. We are
working to help insure that environmental policies take better account
of the complexity and diversity of animal endocrine systems and
contribute to long-term reductions in the production and use of
persistent toxic chemicals. This work builds on the argument made in my
book Pandora's
Poison.
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