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

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

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

What are homeobox genes? (cont’d) Homeodomains either enhance or repress transcription of the genes they bind to, thus regulating activity of the gene. https://wesfiles.wesleyan.edu/courses/biol265/aniridia.htm

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

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

Homeobox Gene Mutation Homeobox mutation Antennapedia in Drosophila http://biology.kenyon.edu/courses/biol114/Chap13/Chapter_13A.html

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

Relevance to Study of Evolution (cont’d) Differences between gradualism model and punctuated equilbrium http://palaeo.gly.bris.ac.uk/benton/reprints/2003eolss.html

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

Role of Gene Duplication in Evolution The mechanism (discussed in an email 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.

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?

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.

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

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

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. 2011. <http://palaeo.gly.bris.ac.uk/benton/reprints/2003eolss.html>. "Drosophila Development." Biology Dept. Kenyon College. Kenyon College. Web. 26 Feb. 2011. <http://biology.kenyon.edu/courses/biol114/Chap13/Chapter_13A.html>.  "Genetic Mutations." The Biology Corner. Web. 26 Feb. 2011. <http://www.biologycorner.com/APbiology/DNA/15_mutations.html>. 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): 771-86. PubMed Central. Web. 26 Feb. 2011. <http://http://www.ncbi.nlm.nih.gov/pmc/articles/PMC34932/>. Li, Guang, and Peter WH Holland. "The Origin and Evolution of ARGFX Homeobox Loci in Mammalian Radiation." BMC Evolutionary Biology 182.10 (2010). Academic Search Premier. Web. 26 Feb. 2011. <http://www.biomedcentral.com/1471-2148/10/182>