Genome sequence of an Australian kangaroo

I have been going through a new paper that presents the genome sequence of tammar wallaby, a small species belonging to the Kangroo family (marsupial lineage). The tammar is unique in its unusual mode of reproduction and development. For one thing the breeding cycle of tammar is highly adapted and synchronized. Tammar is able to delay the embryonic development for a period of 11 months while the embryo is kept in suspended animation (diapause). The delivery of the young occurs always around the same date in January and follows a short period of gestation (26 days). After this the under-developed newborns are transferred to the pouch where they remain for a prolonged period of lactation and development (9-10 months). Therefore most of the development happens in the pouch while the young are exposed to deadly pathogens. During this stage, the composition of milk plays an important role in providing immunity to the young and has to adjust to the different stages of the development. These features make the tammar a unique model organism for genetic studies of reproduction, physiology, immunology and embryonic development.

The sequencing of the tammar was carried out using a combination of shotgun Sanger sequencing, and sequencing using next generation technologies. Whole-genome Sanger approach was used to generate enough sequences of large DNA fragments (2-6Kb) in order to assemble the contigs for de novo assembly. Then ABI SOLiD produced short paired-end reads with large insert sizes which were used to correct the contigs and create the super-scaffolds. The scaffolds were then anchored to markers of the conserved regions in the human genome and genome of a closer relative (Brazilian opossum) in order to construct the seven autosomes and the X, Y chromosomes. It was observed that the genome of tammar is riddled with wide-spread rearrangements compared to that of the eutherians and reptiles (which diverged from marsupials 150M years ago). For example chromosome three consists of genes that exists on nine human chromosomes. The centromere regions are also greatly reduced in size compared to those in the human genome.

The low coverage of the data means many genes in tammar were unsequenced or split in different scaffolds. In spite of this, annotation with Ensembl genebuild led to discovery of more than 18,000 genes and 10,000 GeneScaffolds. To alleviate the problem of missing data, a number of genes were re-sequenced including the HOX gene clusters, major histocompatibility complex (MHC) and the X chromosome, where they made interesting observations: It was observed that most gene families had undergone expansion compared to the eutherian lineage. This is expected since genes duplicate and diverge from each other. The histocompatibility complex which is critical in immunity and recognition of exogenous pathogens, was also found to be highly rearranged where class I genes where moved outside of the complex. The genes on the X chromosome were also extensively reshuffled, although a large number of the non-coding regions were conserved. One imprtant gene XIST was missing which controls the X inactivation in eutherians. It is unclear how this affects the evolution of reproduction as other orthologous genes involved in development were widely conserved. The genome sequence of the HOX genes which are involved in the evolution of morphology were also largely conserved in tammar compared with the humans. Given the strikingly different embryonic morphology between the two species, the question is whether the morphological differences could be attributed to the regulatory elements?

In addition to the genome data, they provide a transcriptome resource and a library of novel microRNAs discovered for tammar. I am still trying to digest all the extensive details. But overall the paper is an enjoyable read and accessible to layman.

 

Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development

Marilyn B Renfree, et al. Genome Biology 2011, 12:R81 doi:10.1186/gb-2011-12-8-r81

Published: 19 August 2011

Abstract (provisional)

Background

We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development.

via Genome Biology | Abstract | Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development.

DNA differences could be linked to diseases

This piece of news by BBC Look East explains what we do at the Sanger Institute.

DNA differences could be linked to diseases

Reseach at the Sanger Institute in Cambridgeshire has led scientists to believe diseases like cancer and diabetes could be linked to minute variations in DNA.

Scientists say minute differences in that pattern, shared by different people, could hold the clue.

via BBC News – DNA differences could be linked to diseases.