Welcome to the Putnam Lab

 
 

Research


After five hundred million years of independent evolution since their divergence in the Pre-Cambrian, metazoan genomes still retain recognizable similarities that allow the partial reconstruction not only of their common ancestors’ protein coding genes, but of its genomic organization (intron-exon structures, organization into chromosomes, and cis-regulatory elements).  There is also new evidence for very ancient conservation of elements of the gene networks controlling body plan and neural patterning.  These recent developments, and the dramatic increase in metazoan diversity spanned by genomic data sets, make comparative genomics a promising approach to some of evolution and development's most important questions:  How do novelty and complexity arise in evolution?  What impact does evolutionary history have on the architecture, function, and future evolution of biological systems?  Our research approaches these questions by coupling the development of novel computational analyses with genomic experiments designed to leverage them.  Our goal is to reconstruct ancestral genomes, pathways, and regulatory networks, and use these reconstructions to test the predictions of models of evolution, and functional hypotheses.


Projects:


Evolution of Genome Organization


It has recently been shown that the organization of animal genomes at the chromosomal scale is preserved in the human genome and in the genomes of very distantly-related animals in other phyla (sea anemones, mollusks, and others; but not in insects or nematodes), and is therefore a relic of, and allows us to reconstruct, the genome organization of ancient animal ancestors going back at least to the last common ancestor of all “eumetazoans” — all animals excluding sponges — and perhaps further.  The biological explanation for this conservation is unknown, but there are two broad possibilities:  either this organization is conserved because it has a role in an unknown mechanism for regulating the genome, or it has no functional importance to the animal, but changes much more slowly than was suggested by previously-available data.  This project aims to answer this question, and investigate the mechanisms and dynamics of genome evolution.


The primary method we employ is computational comparative genomics:  we are building on methods developed by Dr. Putnam as a post-doc in Dan Rokhsar’s lab, comparing the large-scale organization of sequenced genomes (and other genomic data sets) to theoretical models of genome evolution. 


Genome Structure Variation in a Natural Population


The recently-published genome of the Florida lancelet, also commonly called amphioxus (Branchiostoma floridae) showed a very high degree of variation between the two copies of the genome sequenced (polymorphism).  The source DNA for the project was taking from a single wild-caught animal, and therefore contained two copies of the genome:  one inherited from each parent of that individual.  The assembly of the genome was able to reconstruct both of these copies independently for many regions of the genome, providing a large data set in which to examine variations between the two sampled genotypes, including insertions (or deletions) in one relative to the other, and inversions.  The distribution of sequence differences between the two genotypes is consistent with a very large population size, which has been free of dramatic bottlenecks for a long time, making it a potentially useful natural laboratory for studying the rates of various mutational processes, including those that produce structural variation.  We are using this resource to identify structural variants in the data, which serve as the starting point for sampling from the B. floridae population in the Gulf of Mexico.