1. Evolution of Homeobox Genes
Implications and Related Research
Evolution of Homeobox Genes

2. Outline of Topics What are homeobox genes?
Function
Effects of altering these genes
Relevance to the study of evolution
Evolutionary Developmental Biology = Evo Devo
Subject of cutting-edge research
Origin of Arginine-fifty homeobox locus

3. What are homeobox genes?
Encode DNA-binding proteins
These DNA-binding proteins are known as homeodomains.
Comprised of 60 to 63 amino acids
Critical for Embryonic Development
Homeodomains serve as transcription factors that switch genes on and off during embryonic development.
Highly conserved between divergent animal and plant phyla = plesiomorphic

4. What are homeobox genes? (cont’d)
Homeodomains either enhance
or repress transcription of the
genes they bind to, thus regulating activity of the gene.

5. Effects of Altering These Genes
How do we know that this is the function of homeobox genes?
Hox genes  homeobox genes most critical for morphology
Experimental misexpression of these genes
Dramatic phenotypic abnormalities
Cancerous growths
An example: Bart-Jan Janssen et.al. (1997)
Studied effects of overexpression of homeobox gene LeT6 in tomato leaf morphology
Produced variable and unstable morphological states
Suggested that variation in homeobox gene expression could account for diversity in leaf morphology in nature
Critical to the study of Evo Devo

6. Relevance to Study of Evolution
Small mutations in homeobox genes can cause profound effects on an organism’s phenotype.
Large changes in morphology
Example: Mutation of Hox genes in Drosophila melanogaster  produce bizarre morphological features
Extra set of wings
Extra thoracic segment
Legs in location where antennae should be

7. Homeobox Gene Mutation
Homeobox mutation Antennapedia in Drosophila

8. Relevance to Study of Evolution (cont’d)
Dramatic changes in phenotype, and especially morphology
Mechanism for evolution?
Punctuated equilibrium
Rapid evolutionary changes after periods of stasis that result in cladogenesis
Contrary to concept of gradualism which stresses accumulation of small phenotypic changes
Mutation in homeobox gene  Large morphological change  New phyla arise

9. Relevance to Study of Evolution (cont’d)
Differences between gradualism model and punctuated equilbrium

10. Relevance to Study of Evolution (cont’d)
Gene duplication
Gene arises as a duplicate of an existing gene
Descendent has two copies of the same gene
Sets of genes may undergo gene duplication
Example: Hox genes
Is there a correlation between complexity and number of sets of Hox genes?
Yes! It is believed that increasing number of sets may allow for increased complexity
Remember: invertebrates – 1 set, humans – 4 sets, teleost fish –7 sets

11. Role of Gene Duplication in Evolution
The mechanism (discussed in an from Dr. Holland and Dr. Li)
When gene duplication occurs, we have an original copy of the gene and duplicated copy of the gene.
Paralogous genes
Genes are subject to selection.
However, one of the copies may diverge free of selection
It can accumulate mutations and it remains free from selection until it becomes fixed – it acquires a new function.
After new function acquisition, selection resumes.

12. Role of Gene Duplication in Evolution (cont’d)
We now have the original gene with one function, and the duplicate of that gene which has now diverged to have a new function.
Most of the divergent copies of these homeobox genes are eventually erased from the genome through selection, but a few become fixed
Again, possibility that new phyla arise?

13. Origin of Arginine-fifty Homeobox Locus
G. Li and P.W. Holland (2010)
Arginine-fifty homeobox gene (ARGFX) identified in human genome in 2007, but absent in mouse and invertebrate genomes
Unusual given the high level of conservation in homeobox genes
Gene is weakly expressed in human testis and embryonic stem cells, but function is unknown.

14. Origin of Arginine-fifty Homeobox Locus (cont’d)
Purpose of the study
Determine the origin of this unique gene
Attempt to identify the function of the gene
Conclusions
Best answer as of now for the origin of ARGFX
Gene duplication of another more ancient homeobox gene – Otx1, Otx2, or Crx
Function in brain and sensory development
Originated in the lineage of the eutherians (placental mammals)
Still yet, origin of ARGFX is far from conclusive

15. Origin of Arginine-fifty Homeobox Locus (cont’d)
Authors of this study have fully cloned the gene and attempted to prove it to be functional at the protein level
Experiment result was negative
Research on this project is ongoing
Shows us how many questions remain unanswered

16. Works Cited
Benton, Michael J. "PATTERNS AND RATES OF SPECIES EVOLUTION." Palaeobiology and Biodiversity Research Group, Department of Earth Sciences, University of Bristol. Web. 26 Feb <
"Drosophila Development." Biology Dept. Kenyon College. Kenyon College. Web. 26 Feb <
"Genetic Mutations." The Biology Corner. Web. 26 Feb <
Janssen, Bart-Jann, Lance Lund, and Neelima Sinha. "Overexpression of a Homeobox Gene, LeT6, Reveals Indeterminate Features in the Tomato Compound Leaf." Plant Physiology 117.3 (1998):  PubMed Central. Web. 26 Feb <
Li, Guang, and Peter WH Holland. "The Origin and Evolution of ARGFX Homeobox Loci in Mammalian Radiation." BMC Evolutionary Biology  (2010). Academic Search Premier. Web. 26 Feb <