In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Quantitative 
Biosciences
in the School of Biological Sciences

Pedro Marquez Zacarias

Defends his thesis:
Title: Life cycles and nascent multicellularity

Wednesday, August 17, 2022 3:30pm Eastern Time
https://gatech.zoom.us/j/97899556958 Open to the Community
Advisor:
William Ratcliff (School of Biological Sciences, Georgia Tech)
Committee Members:
Peter Yunker (School of Physics, Georgia Tech)
Samuel Brown (School of Biological Sciences, Georgia Tech)
Eric Smith (Earth-Life Science Institute at Tokyo Tech, and Santa Fe Institute) David Murrugarra 
(Department of Mathematics, University of Kentucky)
Abstract:
Life is organized hierarchically. From cells to societies, the levels of biological organization 
shape evolutionary trajectories. These hierarchies are traditionally studied through the lens of 
the Major Evolutionary Transitions (MET) framework. One such major transition is the evolution of 
multicellularity, which gave rise to the evolution of complex life forms like animals, plants, and 
fungi.
First, I will discuss how multicellular organisms differ in their ecology and evolutionary 
trajectories, particularly depending on whether they develop via aggregation (cells coming 
together) or by clonal development (cells staying together). This will lead up to a more general 
question about life cycles, and how are these organized differently in multicellular organisms 
compared to their unicellular counterparts. To give clarity on this matter, I developed a 
compositional algebra to serve as a formal language to represent and analyze life cycles of 
arbitrary complexity. With this algebra, I was able to describe the life cycles of complex and 
simple multicellular organisms and found that organisms that develop via aggregation are more 
similar to unicellular organisms than even simple multicellular organisms. I provide some criteria 
to distinguish between hierarchical levels of reproduction, which I
distinguish from the levels in MET by the features of their life cycles.

Then, I present a simple model of clonal multicellular development that explicitly accounts for 
spatial constraints. In this model, cells have a specific pattern of cell division that can account 
for simple morphological features observed in nascent multicellular organisms. Using this model, I 
was able to directly query the effects of aspect ratio and lateral cell growth, or ‘side-budding’. 
These are two traits known to be important for organismal size in snowflake yeast, which is the 
experimental system we use in the lab to study multicellular evolution. Further, I show how simple 
genetic disruptions to the machinery that controls the patterns of growth in single cell yeast can 
have important effects when applied to snowflake yeast.
Finally, I present a novel method to measure spatial structure in biofilms, which leverages methods 
and concepts from network theory. This method relies on the network representation of a biofilm, 
which gives us flexibility and scalability while preserving as much detail as needed. I show how 
this method is applied to real data, by analyzing microbial communities with cooperative or 
competitive interactions, and showing the detailed spatial information recovered with the proposed 
method.
Altogether, in my thesis work I explored the theme of biological organization: the organization of 
life cycles, the morphological organization of simple multicellularity, and the spatial 
organization of
microbial communities.