YSM Issue 93.1

FOCUS
Molecular Biology
HOW DNA TRAVELS
30 YEARS OF EVOLUTIONARY GENETICS RESEARCH BY BRITT BISTIS
In the era of high-resolution imaging
and advanced computer modeling,
scientists can see a protein’s composition
in great detail and gain extensive
information about its properties and
function. However, these images are only
transient snapshots of the protein. To
better understand protein structure and
function, scientists have more recently
developed powerful experimental and
analytical tools can be applied to deduce a
protein’s provenance and fill in the rest of
the story. One such success story has been
reported by the Schatz Lab at the Yale
School of Medicine, which used cuttingedge
imaging technology to characterize
a Transib transposase protein to elucidate
the evolutionary story of a critical enzyme
in the vertebrate adaptive immune system.
DNA Recombination and Adaptive Immunity
David Schatz, Chair of Immunobiology
and Professor of Immunobiology and
Molecular Biophysics and Biochemistry at
Yale, pioneered his line of research in the
late 1980s as a graduate student at MIT
studying V(D)J recombination, a specific
type of DNA recombination event that
only occurs in developing B and T cells,
and is an integral part of the adaptive
immune system. “Antibody genes and T
cell receptor genes are in a disassembled
nonfunctional state in the germ line
chromosomes. Specifically, these genes
are broken up into small pieces of DNA
called V, D, and J and need to be brought
together by cutting and recombining the
chromosome,” Schatz said. Although the
existence of this type of recombination
was widely accepted in the 1980s, the
nature of the biomolecules carrying out
this process remained elusive.
To discover the genes responsible for
the recombination, Schatz took cells and
transferred large segments of chromosomal
DNA into them to see which combination
of DNAs would yield the recombination
reaction. After extensive experimentation,
Schatz discovered two genes: RAG1 and
RAG2, which together encode the RAG1-
RAG2 recombinase, an enzyme that
facilitates the cutting of the V, D, and J
DNA segments in V(D)J recombination.
“It was a major advancement for the field,”
Schatz said. “Once they were isolated, they
provided the critical tools for studying the
reaction and its regulation.”
18 Yale Scientific Magazine March 2020 www.yalescientific.org