Evo Devo Evo Devo Evolution and Development I

Evo. . . . Devo

Evo - Devo: Evolution and Development I. Background

Evo - Devo I. Background - Embrologists have long realized that organisms in different phyla have different developmental "plans"

Evo - Devo I. Background - Embrologists have long realized that organisms in different phyla have different developmental "plans" - But in a phylum, there is often the same developmental plan. This is not necessarily what we might expect from random mutation and evolution. . . why don't we see as many differences in early developmental traits as we see in later developing traits?

- For instance, why do all chordates have similar development, even though cartilaginous fish and other vertebrates are separated by 400 million years of divergent evolution?

Evo - Devo I. Background - Embryological development is highly conserved, while subsequently allowing extraordinary variation. .

Evo - Devo I. Background II. Core Processes - Basic biological processes are CONSERVED, and the enzymes that perform them are CONSERVED:

Evo - Devo I. Background II. Core Processes - Basic biological processes are CONSERVED, and the enzymes that perform them are CONSERVED: DNA, RNA, protein synthesis - ALL LIFE WHY?

Evo - Devo I. Background II. Core Processes - Basic biological processes are CONSERVED, and the enzymes that perform them are CONSERVED: DNA, RNA, protein synthesis - ALL LIFE Membrane structure and function - ALL EUK's

Evo - Devo I. Background II. Core Processes - Basic biological processes are CONSERVED, and the enzymes that perform them are CONSERVED: DNA, RNA, protein synthesis - ALL LIFE Membrane structure and function - ALL EUK's Cell junctions - ALL METAZOA

Evo - Devo I. Background II. Core Processes - Basic biological processes are CONSERVED, and the enzymes that perform them are CONSERVED: DNA, RNA, protein synthesis - ALL LIFE Membrane structure and function - ALL EUK's Cell junctions - ALL METAZOA Hox genes - ALL BILATERIA

Evo - Devo I. Background II. Core Processes - Basic biological processes are CONSERVED, and the enzymes that perform them are CONSERVED: DNA, RNA, protein synthesis - ALL LIFE Membrane structure and function - ALL EUK's Cell junctions - ALL METAZOA Hox genes - ALL BILATERIA Limb formation - ALL LAND VERTEBRATES

Evo - Devo I. Background II. Core Processes - Basic biological processes are CONSERVED, and the enzymes that perform them are CONSERVED: - Many enzymes are more than 50% similar in AA sequence in E. coli and H. sapiens, though separated by 2 billion years of divergence. - Of 548 metabolic enzymes in E. coli, 50% are present in ALL LIFE, and only 13% are unique to bacteria.

Evo - Devo I. Background II. Core Processes - Basic biological processes are CONSERVED, and the enzymes that perform them are CONSERVED: - Many enzymes are more than 50% similar in AA sequence in E. coli and H. sapiens. - Of 548 metabolic enzymes in E. coli, 50% are present in ALL LIFE, and only 13% are unique to bacteria. - So the variation and diversity of life is NOT due to changes in metabolic or structural genes. . . we are all built out of the same stuff, that works the same way at a cellular level.

Evo - Devo I. Background II. Core Processes - Basic biological processes are CONSERVED, and the enzymes that perform them are CONSERVED: - Many enzymes are more than 50% similar in AA sequence in E. coli and H. sapiens. - Of 548 metabolic enzymes in E. coli, 50% are present in ALL LIFE, and only 13% are unique to bacteria. - So the variation and diversity of life is NOT due to changes in metabolic or structural genes. . . we are all built out of the same stuff, that works the same way at a cellular level. - Variation is largely due to HOW these processes are REGULATED. . . 300 cell types in humans, all descended from the zygote; all genetically the same.

Evo - Devo I. Background II. Core Processes III. Weak Linkage Regulation - Development is NOT a single process Muscle development

Evo - Devo I. Background II. Core Processes III. Weak Linkage Regulation - Development is NOT a single process - Development is a well choreographed dance of many parallel processes. . . Muscle development Bone development

Evo - Devo I. Background II. Core Processes III. Weak Linkage Regulation - Development is NOT a single process - Development is a well choreographed dance of many parallel processes. . . - How is the parallelism maintained, ESPECIALLY as one process evolves? Muscle development Bone development

Evo - Devo I. Background II. Core Processes III. Weak Linkage Regulation - Development is NOT a single process - Development is a well choreographed dance of many parallel processes. . . - How is the parallelism maintained, ESPECIALLY as one process evolves? - Because they may be triggered by the same (or subsets of the same) REGULATORS. . . these are transcription factors that can turn suites of metabolic/structural genes on and off. Muscle development Nerve development

Evo - Devo I. Background II. Core Processes III. Weak Linkage Regulation - Development is NOT a single process - Development is a well choreographed dance of many parallel processes. . . - How is the parallelism maintained, ESPECIALLY as one process evolves? - Because they may be triggered by the same (or subsets of the same) REGULATORS. . . these are transcription factors that can turn suites of metabolic/structural genes on and off. And transcription factors can interact. Muscle development Nerve development

Evo - Devo I. Background II. Core Processes III. Weak Linkage Regulation - Best (and most fundamental) examples are HOX genes. These are 'homeotic genes' that produce a variety of transcription factors. The production and localization of these transcription factors are CRITICAL in determining the 'compartments' of bilaterally symmetrical animals.

Evo - Devo antennaepedia I. Background II. Core Processes III. Weak Linkage Regulation - Change activity of hox gene ‘antennaepedia’ in head – grow legs on head. - But it takes 100’s of co-ordinated genes to regulate the growth and specialization of cells into tissues to make a leg. How is this all coordinated? Ultimately, change in same stimulus (antennaepedia transcription factor). Muscle development Nerve development

Evo - Devo I. Background II. Core Processes III. Weak Linkage Regulation - Mutations are in regulatory gene or cis regulatory element (CRE) - These are only active in particular tissues, anyway, so the affect is localized. A mutation in the structural gene would affect ALL tissues where that gene is expressed. Bithorax

There are MULTIPLE binding sites upstream from each gene. Here are the biding sites for transcription factors that regulate the human metallothionein II gene. 1. Suppose AP 2 is produced in nerve tissue, turning this gene on in nerves

There are MULTIPLE binding sites upstream from each gene. Here are the biding sites for transcription factors that regulate the human metallothionein II gene. 1. Suppose AP 2 is produced in nerve tissue, turning this gene on in nerves 2. But suppose Gluc. Recept. is produced in muscle, turning this on in muscle

There are MULTIPLE binding sites upstream from each gene. Here are the biding sites for transcription factors that regulate the human metallothionein II gene. 1. Suppose AP 2 is produced in nerve tissue, turning this gene on in nerves 2. But suppose Gluc. Recept. is produced in muscle, turning this on in muscle 3. Now, suppose there is a mutation in the GRE binding sequence. This mutation is inherited by ALL cells, but will only depress production in muscle, where gene action was regulated by the binding of Gluc. Recept.

There are MULTIPLE binding sites upstream from each gene. Here are the biding sites for transcription factors that regulate the human metallothionein II gene. 1. Suppose AP 2 is produced in nerve tissue, turning this gene on in nerves 2. But suppose Gluc. Recept. is produced in muscle, turning this on in muscle 3. Now, suppose there is a mutation in the GRE binding sequence. This mutation is inherited by ALL cells, but will only depress production in muscle, where gene action was regulated by the binding of Gluc. Recept. - Metallothionine is still made elsewhere. (A mutation in the GENE would turn it off everywhere)

There are MULTIPLE binding sites upstream from each gene. Here are the biding sites for transcription factors that regulate the human metallothionein II gene. 1. Suppose AP 2 is produced in nerve tissue, turning this gene on in nerves 2. But suppose Gluc. Recept. is produced in muscle, turning this on in muscle 3. Now, suppose there is a mutation in the GRE binding sequence. This mutation is inherited by ALL cells, but will only depress production in muscle, where gene action was regulated by the binding of Gluc. Recept. - Metallothionine is still made elsewhere. (A mutation in the GENE would turn it off everywhere) - The Glucocorticoid Receptor is still functional and works elsewhere else.

Evo - Devo I. Background Gene for transcription factor II. Core Processes III. Weak Linkage Regulation - Types of Regulation Transcription factor CRE’s: Binding sites for transcription factors that may repress or enhance expression of structural gene

Evo - Devo mutation in the transcription factor gene is called trans-regulation I. Background II. Core Processes III. Weak Linkage Regulation - Types of Regulation Mutation here is cis-regulation (within the operational "cistron")

Evo - Devo I. Background II. Core Processes III. Weak Linkage Regulation - NOVELTY: Typically by GENE DUPLICATION and MUTATION of gene and regulatory sequences (cis elements) On in new tissue?

Typically, E. coli is unable to metabolize citrate if oxygen is present. In Lenski’s 25 year experiment, he isolated a strain that could metabolize citrate as a food stuff when oxygen was present. Dramatic population growth in oxygenated environment by metabolizing citrate.

In the ancestral condition, the cit. T gene is only expressed in the absence of oxygen, and it encodes a transport protein that pumps citrate in for metabolism.

In the new lineage, there was duplication of the cit. T gene, and it was placed next to the rnk promotor (yellow), which is activated when oxygen is present. So now, cit. T ON when O 2 PRESENT

Evo - Devo I. Background II. Core Processes III. Weak Linkage Regulation - Duplication and mutation of of hox genes and/or their cis regulatory elements led to differential regulation in different segments, and different phenotypes in different segments. inhibition of limb development

Evo - Devo I. Background Gene 1 II. Core Processes III. Weak Linkage Regulation - different hox genes produce different binding proteins, that stimulate different sets of genes. . . that are ALL regulated by THIS transcription factor (linked regulation coordinated response). Hox gene 1 Gene 2 Gene 3 Gene 4

Duplication of entire cluster TWICE in chordates, giving four sequences. Subsequent deletions of particular genes in each cluster.

Change in Regulation A major developmental difference between protostomes and deuterostomes is the dorso-ventral axis: PROTO: digestion dorsal, neural ventral DEUTERO: digestion ventral, neural dorsal Co-ordinated by homologous genes (same color) that are activated oppositely.

Limb development is also governed by a set of homologous genes ‘engrailed’ ventral End of limb dorsal End of limb Engrailed produces a transcription factor that turns on gene for ‘hedgehog’ protein, which diffuses into neighboring cells. Lo [En] and hi [Hh] stimulate Dpp wg

And in vertebrates, it is the regulation of these genes that creates a leg from a fin…. FISH – hoxd 13 a gene stalls in mid-development. TETRAPODS – hoxd 13 a stalls, and then is expressed again later – initiation formation of a limb bud Feitas et al. used a hormone to re-stimulate the expression of hoxd 13 a in fish fin… creating a rudimentary limb bud.

Evo - Devo I. Background II. Core Processes III. Weak Linkage Regulation - Novelty: gene replication and mutation of gene and regulatory elements - Allometry: changes in relative rates of growth

Lisa Cooper and Karen Sears. 2013. How to grow a bat wing. In Bat evolution, ecology, and conservation. 1. BMP-2 causes apoptosis in interdigital spaces in other vertebrates. This is inhibited in bats by ‘gremlin’ and also by fgf-8, which continues cell proliferation of the interdigital membrane. 2. But bmp-2 causes the elongation of long bones, too, and this continues in bat digits while it is inhibited in mice.

Allometry in horn length relative to body size in Beetles Scarabaeidae: Onthophagus

Example - Darwin's Finches - two genes interact in a co-ordinated way to determine beak dimensions (Abzhanov et al. 2006. Nature 442: 563 -567).

Example - Darwin's Finches - two genes interact in a co-ordinated way to determine beak dimensions (Abzhanov et al. 2006. Nature 442: 563 -567). - BMP 4 i a highly conserved signaling molecule in all metazoa; it is "bone morphogen protein" that stimulates collegen production and subsequent production of cartilage and bone.

Example - Darwin's Finches - two genes interact in a co-ordinated way to determine beak dimensions (Abzhanov et al. 2006. Nature 442: 563 -567). - BMP 4 i a highly conserved signaling molecule in all metazoa; it is "bone morphogen protein" that stimulates collagen production and subsequent production of cartilage and bone. - The timing and amount of BMP 4 varies during development of finches;

Example - Darwin's Finches - two genes interact in a co-ordinated way to determine beak dimensions (Abzhanov et al. 2006. Nature 442: 563 -567). - BMP 4 i a highly conserved signaling molecule in all metazoa; it is "bone morphogen protein" that stimulates collegen production and subsequent production of cartilage and bone. - The timing and amount of BMP 4 varies during development of finches; - Large Ground Finch produces more, and produces it earlier, than other species.

Example - Darwin's Finches - two genes interact in a co-ordinated way to determine beak dimensions (Abzhanov et al. 2006. Nature 442: 563 -567). - BMP 4 i a highly conserved signaling molecule in all metazoa; it is "bone morphogen protein" that stimulates collegen production and subsequent production of cartilage and bone. - The timing and amount of BMP 4 varies during development of finches; - Large Ground Finch produces more, and produces it earlier, than other species. - And a second, Calmodulin, is expressed more in long pointed beaks. Ca. M modulates calcium signalling in cells

Example - Darwin's Finches - two genes interact in a co-ordinated way to determine beak dimensions (Abzhanov et al. 2006. Nature 442: 563 -567).

Example - Darwin's Finches - two genes interact in a co-ordinated way to determine beak dimensions (Abzhanov et al. 2006. Nature 442: 563 -567). Used a virus to insert an up regulator of Ca. M into the beak of growing chick embryos. This is a kinase that increases absorption of Ca. M. Caused beak elongation.

Example - Darwin's Finches - so, allometry like this is a common source of adaptive variation that may often be involved in adaptive radiations. - This variation is in the developmental timing of action of the same structural genes.

Evo - Devo I. Background II. Core Processes III. Weak Linkage Regulation - Novelty: - Allometry: - Vestigial Embryology: Hind limb bud in dolphin

Loss of limbs in snakes: Hox. C 8 and Hox. C 6 are active in ‘trunk’ segments of the thorax in humans and chicks, and block limb development. They are active in most segments of snakes, blocking limb development. Also, shh is reduced in limb buds of snakes, so bud does not develop and is reabsorbed, as in cetaceans.

Loss of limbs in snakes: Also, shh is reduced in limb buds of snakes, so bud does not develop and is reabsorbed, as in cetaceans.

Evo - Devo I. Background II. Core Processes III. Weak Linkage Regulation - Novelty: - Allometry: - Vestigial Embryology: - Gene Recruitment: using what you have in a new place

Evolution of the eye

Evolution of Camera Eye - Opsins Although all eyed animals have multiple opsins (c, r, g), they are used differently by different types of organisms. Verts – c-opsins in photoreceptors, ropsins in intermediary cells in retina. Inverts – r-opsins in eyes, c-opsins in brain.

Evolution of Camera Eye - Vertebrates Crystallins are heat-shock proteins in other cells, but when secreted by surface cells of the eye, their transparent nature made for an efficient lens.

Invertebrate Camera Eye - Mollusks

Evolution of the eye ‘eyeless’ Hox gene for eye development Pax-6