Evolution and genetic architecture of the first mitotic spindle in C. elegans

Date

Apr 2, 2014

Time

2:00 PM - 3:00 PM

Speaker

Daniel Needleman

Affiliation

Harvard University

Language

en

Main Topic

Biologie

Other Topics

Biologie

Host

Jan Brugues

Description

The architecture and dynamics of sub-cellular structures show remarkable variations between species, but little is known about the evolutionary or mechanistic basis of this diversity. Examining intraspecies variation can provide valuable evolutionary insights because the short evolutionary distances involved allow process to be dissected in detail, but the extent of intraspecific variation of sub-cellular traits is unknown. We are using the first embryonic division in C. elegans to study the evolution of the mitotic spindle, the subcellular structure that segregates chromosomes during cell division. We developed a high-throughput microscopy platform and automated image analysis software that allows us to obtain quantitative information on the structure and dynamics of spindles from tens of thousands of embryos in hundreds of lines. We found extensive standing genetic variation among natural isolates of C. elegans for all traits we studied including: cell size; the size and motion of pronuclei; the length, motion, and speed of elongation of the spindle; the size of centrosomes; the positioning of the cleavage plane. We are studying the genetic architecture of these traits by performing a genome wide association analysis and by characterizing a panel of recombinant inbred advanced intercross lines. Mutations are the ultimate source of variation between individuals. Understanding how spontaneous mutations affect sub-cellular structures shows what phenotypes are evolutionary accessible and provides a "baseline" of how these traits would change in the absence of selection. We studied how spontaneous mutations modify the spindle by characterizing cell division in a panel of mutation accumulation (MA) lines - created by propagating an initially genetically identical set of lines at low effective population size for ~250 generations. Comparing the spectrum of variations in MA lines to those we observe among natural isolates allows us to draw inferences about how selection and population dynamics combine with raw mutational inputs to shape the spindle in C. elegans. Taken together, our data suggests that cell size is under stabilizing selection in C. elegans and that variations in cellular traits are largely controlled by their correlations with cell size and with each other. This simple model also largely accounts for the variations in cell division between different species of nematodes, which we characterize through a detailed study of ~40 additional species of known phylogeny. Our results suggest that combining cell biology, biophysics, and quantitative genetics will produce novel evolutionary and mechanistic insights.

Last modified: Apr 3, 2014, 9:48:51 AM