Learning Goal Understand the evolution of complexity

Expected Learning Outcomes 1)Visualize fitness as a function of gene function for one and two genes with and without pleiotropy 2)Construct and explain a plausible model for the evolution of increased complexity 3)Describe and discuss the role of gene duplication and pleiotropy in the evolution of complexity 4)Infer the history of gene duplication and shifts in gene function using phylogenetic inference

History of Life Last universal common ancestor was a derived, complex organism First common ancestor was a very simple organism

Complex Unicellular Life

Complex Unicellular Life Complex Multicellular Life

Complexity Complexity evolves by the piece-meal addition and modification of existing parts and the sorting of variation by natural selection over long periods of time.

Origin of Life Hypercycles

The First Gene? epistasis self-replicating ribozymes consolidation pleiotropy Gene Proofreading Metabolism Synthesis

The First Gene gene functions pleiotropy Proofreading Metabolism Synthesis

Pleiotropy gene pleiotropy Replication Proofreading Metabolism Synthesis How many functions are possible? What is the limit to the number of different functions that can be encoded by a gene? functions

Graph Draw a frequency distribution showing what you might expect if you examined each gene and recorded the number of different functions each gene performed (i.e. pleiotropy) pleiotropy Pleiotropy (Number of different functions) Number of genes

Choose Your Graph A) B) C) D) E) None of these are my graph

Observed Pleiotropy From Wagner and Zhang Nature Genetics Reviews Yeast: a highly derived eukaryote Only 1 function Seven different functions

A More Complex Critter From Wagner and Zhang Nature Genetics Reviews

Graph It Number of different functions Efficiency of a particular function How does pleiotropy influence the ability of the gene product to perform a specific function?

ABCDABCD E) My graph not shown

Evolutionary Model gene pleiotropy

The Fitness Model Draw a graph of function (x- axis) versus fitness (y-axis) that represents a model for antagonistic pleiotropy W Function 1 2 Function

Redundancy Partial sub- functionalization Full sub- functionalization What does your graph look like? Fitness Function Fitness Function Fitness Function Fitness Function A B C D 1 2 Function E) My graph is not shown

  Given the model, what is the expected function in the population?     C)The function where the two lines cross D)The average of   and  . Functio n Fitness 1 2

  Function Fitness X

  1 2 On a piece of paper, draw this graph and use it as a model to show the fitness cost of pleiotropy relative to a model in which there is not antagonistic pleiotropy Functio n Fitness

Functio n A Fitness   1 2 B C D Choose the value that best represents the fitness cost of antagonistic pleiotropy relative to a model without pleiotropy.

Fitness cost of pleiotropy Function a b Fitness   1 2

Subfunctionalization Pleiotropy Fitness Function a b Fitness cost of pleiotropy Optimum Ancestral Condition

Gene Duplication gene pleiotropy gene Duplication redundant pleiotropy

Subfunctionalization Redundancy Partial sub- functionalization Pleiotropy Fitness Function a b Mutation Selection Reduced pleiotropy

Function Blue Red Fitness   New expected fitness

Function Fitness   New expected fitness A B C D E Choose the expected trait value (function) for the red gene after the blue gene undergoes subfunctionalization A) A B) B C) C D) D E) E

Subfunctionalization Redundancy Partial sub- functionalization Full sub- functionalization Pleiotropy No pleiotropy Fitness Function a b Mutation Selection Mutation Selection Reduced pleiotropy

Draw the Fitness Model for the Derived Condition Full sub- functionalization Pleiotropy No pleiotropy Fitness Gene Function a b ? Ancestral Derived

Conceptual Model Full sub- functionalization PleiotropyNo pleiotropy Fitness Gene Function a b Fitness Gene Function a Single peak b

Conceptual Model Full sub- functionalization PleiotropyNo pleiotropy Fitness Gene Function a b Fitness Gene Function a b Two-fold increase in complexity One axis to two

Neofunctionalization Redundancy Partial sub- functionalization Neofunctionalization Time New function Mutation Selection Mutation Selection

What Does This Fitness Model Look Like? New function Fitness Gene Function

Visualization New function Fitness Gene Function Multiple Peaks

How Would You Visualize the Model with a Third Independent Variable? (i.e 3 genes)

Visualization With Three Genes Gene 3 Gene 1 Gene 2 Fitness High Low

Thinking About Duplication and Functional Divergence in the Context of Phylogeny

Functions Gene expression Genes One gene Two functions Two genes Each gene has two functions Three genes Each gene has one function

Gene Functions Note on the tree where gene duplication, subfunctionalization and neofunctionalization happen using parsimony D = Duplication S = Subfunction N = Neofunction Gene

Note on the tree where gene duplication, subfunctionalization (subfunction) and neofunctionalization (neofunction) happen using parsimony A)1 = duplication, 2 = subfunction, 3 = neofunction B)1 = neofunction, 2 = subfunction 3 = duplication C)1 = subfunction, 2 = neofunction, 3 = duplication D)1 = duplication, 2 = neofunction 3 = subfunction 3 2 1

Gene Functions Note on the tree where gene duplication, subfunctionalization and neofunctionalization happen using parsimony D = Duplication S = Subfunction N = Neofunction D S N

Gene Functions Infer the history of gene duplication, loss and functional modification Note the ancestral states for each internal node D = Duplication S = Subfunction N = Neofunction L = Gene loss Gene Nodes

Regulatory Genes

History of Gene Duplication