The Wyckoff Lab
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 Research Focus & Philosophy
 While constraint and random genetic drift are the primary forces acting on the evolution of most gene sequences over evolutionary time, positive selection does happen at the molecular level and can play a significant role in the development of specific gene sequences. By quantifying the nature of positive and negative selection within and between species, the role that different types of selection can play on the overall "adaptation" of an organism to it's environment can eventually be explored. It is the interplay between these forces and how they can be measured that interests me.

Comparative Genomics:
I have developed a methodology to search for the contrasting effects of positive and negative selection by looking at the physico-chemical properties of amino acids which are differing between species (Wyckoff, Wang, and Wu, 2000). I have also extended this work to a larger data set between humans and old world monkeys (OWM), and have examined human polymorphism in order to determine the rate of fixation of selectively advantageous mutations in primates (Fay, Wyckoff, and Wu, 2001). As I have been collaborating with Dr. Chung-I Wu looking at data coming from a consortium of people working on Macaca fascicularis testis and brain cDNA library sequence, the lab is building in large part upon this work. In addition, we have preliminary data on several reproduction related genes and we are interested in examining these genes more thoroughly. These projects are well suited for graduate thesis work and undergraduate research projects.

Polymorphism analysis:
By extensive human coding region sequence analysis and evolutionary comparisons to outgroup primate species, an appropriate weighting factor can be derived for nonsynonymous polymorphisms. The goal is to use this weighting method to help determine the likelihood that a specific mutation isolated by any of a variety of methods as putatively disease causing is indeed causal within a given population. In addition, the interface between complex disease mapping and evolutionary genomics can provide information which informs mapping experiments while mapping experiments provide data for further evolutionary analysis. This is a major part of the work taking place in the lab to date.

A major effort during my postdoctoral research was to obtain the resources necessary to put together a relational database of genomic sequences and associated information. This includes expression information, divergence information, polymorphism information, and disease linkage information. We envision several types of publications coming directly from the techniques and programs built to handle and query the data, but more importantly, observations made using this tool will lead to hypothesis testing experiments performed at the bench. We in the lab actively seek collaborations with people who work in a variety of systems, including in model organisms such as mice, yeast, and Drosophila, where experimental manipulation of genes and gene pathways will allow for the testing of the effects of predictions made in silico.

design: brainchild