Evolution of coding and non-coding genes in HOX clusters of a marsupial.
BACKGROUND
The HOX gene clusters are thought to be highly conserved amongst mammals and other vertebrates, but the long non-coding RNAs have only been studied in detail in human and mouse. The sequencing of the kangaroo genome provides an opportunity to use comparative analyses to compare the HOX clusters of a mammal with a distinct body plan to those of other mammals.


RESULTS
Here we report a comparative analysis of HOX gene clusters between an Australian marsupial of the kangaroo family and the eutherians. There was a strikingly high level of conservation of HOX gene sequence and structure and non-protein coding genes including the microRNAs miR-196a, miR-196b, miR-10a and miR-10b and the long non-coding RNAs HOTAIR, HOTAIRM1 and HOXA11AS that play critical roles in regulating gene expression and controlling development. By microRNA deep sequencing and comparative genomic analyses, two conserved microRNAs (miR-10a and miR-10b) were identified and one new candidate microRNA with typical hairpin precursor structure that is expressed in both fibroblasts and testes was found. The prediction of microRNA target analysis showed that several known microRNA targets, such as miR-10, miR-414 and miR-464, were found in the tammar HOX clusters. In addition, several novel and putative miRNAs were identified that originated from elsewhere in the tammar genome and that target the tammar HOXB and HOXD clusters.


CONCLUSIONS
This study confirms that the emergence of known long non-coding RNAs in the HOX clusters clearly predate the marsupial-eutherian divergence 160 Ma ago. It also identified a new potentially functional microRNA as well as conserved miRNAs. These non-coding RNAs may participate in the regulation of HOX genes to influence the body plan of this marsupial.
ARC Centre of Excellence in Kangaroo Genomics, The University of Melbourne, Melbourne, Victoria 3010, Australia.
Hongshi
H
Yu
James
J
Lindsay
Zhi-Ping
ZP
Feng
Stephen
S
Frankenberg
Yanqiu
Y
Hu
Dawn
D
Carone
Geoff
G
Shaw
Andrew J
AJ
Pask
Rachel
R
O'Neill
Anthony T
AT
Papenfuss
Marilyn B
MB
Renfree
D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence / Q000235:genetics; D018983:DNA Footprinting; D019143:Evolution, Molecular; D005801:Genes, Homeobox / Q000235:genetics*; D023281:Genomics / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007614:Macropodidae / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D058977:Molecular Sequence Annotation; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D022661:RNA, Untranslated / Q000235:genetics*; D016415:Sequence Alignment; D013737:Testis / Q000378:metabolism
D035683:MicroRNAs; D022661:RNA, Untranslated