I develop mathematical, computational, and conceptual models to study complex phenotypes.
Earlier in my career, I focused on how evolutionary and genetic processes shape reproductive and behavioral traits. It was necessary at that time to treat as a black box many of the genetical and physiological details that determine phenotypes, and to focus in a general way on how natural selection influences phenotypes over very broad assumptions about underlying mechanisms. Some examples can be found in my summary below on past research.
My research has changed in the past few years, following the great changes in modern biology. It is now possible to see below the surface of complex phenotypes to the biochemical and genetical mechanisms that control those characters. I have continued to focus on complex phenotypes as I did earlier in my career, but now with particular emphasis on how the quantitative dynamics of genetical, biochemical, and cellular mechanisms determine those phenotypes, and how evolutionary processes in turn shape the mechanisms and dynamics that give rise to phenotypes.
The integration of mechanistic and evolutionary analyses is the theme of my book, Immunology and Evolution of Infectious Disease, and of my various recent studies on host-parasite interactions. At this point, I have finished much of the conceptual background and the first stages of quantitative modeling. I am now pursuing the next steps of this work through collaborations with experimental laboratories, using the mathematical and computational models to design experiments. The long-term goal is to understand how various mechanistic components determine complex aspects of host immunity and parasite escape, and how evolutionary processes have shaped the underlying mechanisms.
I have recently developed a new line of work on cancer. Cancer might be described as an evolutionary process within individuals that changes the normal regulatory interactions governing cellular birth and death rates. This is a fascinating problem for an evolutionary biologist, because one must understand the short-term evolutionary processes within individuals that disrupt normal regulation, and the long-term evolutionary processes that have shaped the normal network of regulatory controls on cellular dynamics.
The fantastic progress of modern biology at the genetical, biochemical, and cellular levels of cancer once again provides an opportunity to link mechanistic models of complex phenotypes to the evolutionary processes that shape mechanisms. My early work on cancer focused on epidemiological data, linking mechanistic, quantitative models of progression within individuals to rates of incidence in populations. In my recent book, Dynamics of Cancer: Incidence, Inheritance, and Evolution, I start with incidence rates in populations and then develop a deeper understanding of mechanistic details, quantitative models of phenotypes (cellular regulation and cancer progression), and evolutionary processes.
I am also working on how regulatory control networks shape phenotypes. This arises as a fundamental part of studying immunology and cellular proliferation in cancer. One puzzle is how different types of regulatory control structures accumulate germline mutations and therefore lead to different patterns of genetic heterogeneity for complex phenotypes. I have written briefly on this topic, and intend to pursue this subject through the examples of immunology and cancer to develop a more realistic understanding of network architecture and genetic heterogeneity. Another interesting topic is how natural selection shapes the architecture of regulatory networks. In the future, I would also like to work again on symbiosis, to integrate the many recent advances in the biochemistry and genetics of microorganisms with the conceptual issues of replication, conflict and cooperation to which I contributed in the 1990s.
Through much of my career, I have been interested in coevolutionary interactions that lead to conflict or cooperation. These interactions occur at many different levels of biological organization: between members of the same population (social behavior), between different genetic elements within a genome, and between host and pathogen populations. This broad view led me to study coevolutionary interactions in a variety of systems.
(1) I have studied sex allocation, which is the division of resources to sons and daughters, or, more generally, to male and female reproductive function. Sex allocation has played an important role in the study of social behavior because (a) many aspects of reproductive competition affect the relative value of sons and daughters, for example, sexual selection or conflict among genetic relatives; (b) the methods required for analyzing sex allocation problems apply to several questions in adaptation, for example, frequency dependent selection or genetic constraints such as sex chromosomes; and most importantly, (c) numbers of males and females and investment in each are relatively easily measured traits. Perspectives on adaptation and social evolution can therefore be tested by studying sex allocation. My book Foundations of Social Evolution summarizes much of this work.
(2) I have worked on theories of genomic conflict. Different parts of the genome are transmitted in different ways, and therefore may have conflicting reproductive interests. For example, mitochondria are transmitted mostly from mother to daughter, whereas autosomes are passed equally to both sons and daughters. Mitochondria and other matrilineal elements therefore favor a female-biased sex ratio, whereas autosomes tend to favor an equal sex ratio. Conflicting modes of genetic transmission cause many interesting traits, such as cytoplasmic male sterility in plants, sex ratio biasing bacterial and viral symbionts, and high frequencies of transposable genetic elements. Many aspects of genomic organization and patterns of genetic variation can only be understood in the context of genomic conflict.
(3) I have developed theoretical models to analyze the coevolutionary genetics of hosts and parasites. Populations often contain high levels of genetic polymorphism for resistance to pathogens. The effectiveness of this resistance is limited because the pathogens are, in turn, widely polymorphic for host-range genes that can escape host resistance. In addition to the variability found within populations, the frequency of particular host and parasite genes may vary widely over small geographic areas (metapopulation dynamics).
(4) The host-parasite work emphasizes evolutionary dynamics on the conflict side of my interest in conflict and cooperation. I have also studied the evolution of mutual harm or benefit in symbiosis. For example, the more a parasite harms its host (virulence) the more it damages its food supply. But the costs of virulence may be offset by increased competitive success against other parasites within the host or by greater transmission to other hosts. This problem of virulence can be generalized by considering parasite and host genes as replicators that live within a shared compartment (body). The different replicators have a shared interest in using the body's resources prudently, but also conflict over the distribution of resources. This general view of symbiosis applies to the evolution of protocells and genetic systems near the origin of life, to genomic conflict, to the evolution of ecological mutualisms, and to the evolution of group living and social behavior.
(5) My other research interests include population genetics, the history of evolutionary theory, evolutionary aspects of adaptation and development, and the biology of figs.
Click images for information, links, and downloading of my books