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  current news   Press   selected story    
     
  28 March 2014  
  Congratulations to IMCB's recent PhD Graduate
 
 



Thesis title: 
Sequencing and characterization of Hox gene clusters in Japanese lamprey (Lethenteron japonicum)


Abstract 

Cyclostomes (comprising lampreys and hagfishes) are the sister group of living jawed vertebrates (gnathostomes) and are therefore an important group for understanding the origin and diversity of vertebrates. In vertebrates and other metazoans, Hox genes determine positional identities along the developing embryo and are implicated in driving morphological diversity. Invertebrates typically contain a single Hox cluster whereas tetrapods contain four Hox clusters owing to two rounds (‘1R’ and ‘2R’) of whole-genome duplication during early vertebrate evolution. By contrast, most teleost fishes contain up to eight Hox clusters due to an additional teleost-specific genome duplication event. In my project, using a combination of sequences from BAC clones and a draft genome assembly, I provide evidence for at least six Hox clusters in the Japanese lamprey (Lethenteron japonicum). Unlike the compact gnathostome Hox clusters, lamprey Hox clusters are large and highly repetitive and are therefore organized more like the single invertebrate Hox cluster. Cis-regulatory elements can be identified as conserved noncoding elements (CNEs). By aligning the lamprey Hox clusters with the four Hox clusters of elephant shark and human, I identified several CNEs. Transgenic zebrafish assays indicated the potential of selected CNEs to function as cis-regulatory elements, driving reporter gene expression resembling the expression pattern of Hox genes in the vicinity of CNEs.

The presence of more than four lamprey Hox clusters suggests that its lineage has experienced an additional round of genome duplication similar to teleosts. Further support for the additional genome duplication is provided by the presence of additional non-Hox gene/gene family paralogs in the Japanese lamprey genome compared to the human genome. Because of the GC-bias of the lamprey genome, which affects codon usage patterns and amino acid composition, phylogenetic analysis was not informative for timing the 1R and 2R events relative to lamprey and gnathostome divergence. Alternatively, I sought clues about the timings of 1R and 2R by analyzing the Hox clusters of lamprey and gnathostomes. First, the synteny of genes linked to each lamprey Hox cluster is different to those linked to gnathostome Hox clusters. Secondly, individual lamprey Hox clusters share CNEs across four paralogous elephant shark and human Hox clusters suggesting a many-to-many orthology relationship between lamprey and gnathostome Hox clusters. These independent lines of evidence suggest that the first two rounds (1R and 2R) of genome duplications occurred after the divergence of lamprey and gnathostome lineages.

Figure

Figure legend: Hox gene loci in Japanese lamprey. Hox genes are shown as blue boxes whereas non-Hox genes are shown as white boxes. Arrows denote the direction of transcription; pseudogenes are marked with a Ψ symbol and the ends of scaffolds are represented by black circles. An interesting feature is the presence of eight Hox-4 genes which indicates that the Japanese lamprey may contain up to eight Hox clusters. The presence of more than four Hox clusters provides evidence for an additional round of genome duplication in the lamprey lineage.

Publication:
Mehta, T.K., Ravi, V., Yamasaki, S., Lee, A.P., Lian, M.M., Tay, B., Tohari, S., Yanai, S., Tay, A., Brenner, S. and Venkatesh, B.  Evidence for at least six Hox clusters in the Japanese lamprey (Lethenteron japonicum). Proc. Natl. Acad. Sci. USA. (2013) 110: 16044-16049.

For more information on Byrappa VENKATESH’s laboratory, please click here.