The Evolution of Gene Arrangements and Gene Families in Tammar Wallaby

Abstract

As a representative of Australian marsupials, the recently sequenced genome of a model kangaroo, the tammar wallaby (Macropus eugenii) provides unique opportunities to understand the organisation and evolution of the genome in marsupials, and in mammals in general. Comparisons with the fully sequenced genome of the Brazilian short-tailed opossum Monodelphis domestica allow comparing the genomes of American and Australian marsupials. The general aims of this thesis were to examine the extent to which part of the genome has been conserved in marsupials and in therian mammals, as well as to explore the organisation and evolution of the largest gene family in mammals, whose members code for olfactory receptors. As part of the KanGo’s task of establishing a map of the tammar genome, the comparative map of the long arm of chromosome 6 in the tammar wallaby was prepared. Several syntenic blocks of genes were mapped to tammar wallaby 6q and it was found that there are only few rearrangements between the tammar wallaby and the opossum in this part of the genome. However, the genomic parts orthologous to tammar wallaby 6q reside on several chromosomes in human, dog, and chicken, suggesting that the fusion occurred in the marsupial ancestors and remained conserved during marsupial evolution. I then developed a strategy to explore the OR gene (ORG) family in the tammar wallaby. Sequences corresponding to ORGs were extracted from the first assembly of the tammar wallaby genome and sequences classified into families and subfamilies. BACs bearing conserved mammalian ORG clusters were isolated and physically mapped in tammar wallaby. Comparison with the opossum OR repertoire revealed that these two distantly related marsupials share a very similar ORG superfamily. Conserved features include the total numbers of genes, families, and subfamilies, gene distribution across the families and subfamilies, patterns of expansions and contractions in families and subfamilies and genomic location of major ORG clusters. I then examined in detail the genomic organisation of a highly conserved ORG cluster that lies near the MHC locus in several mammals. By making a BAC contig over the entire chromosome region I found that this cluster is conserved in tammar wallaby and carries almost the same genes as in the opossum. Preliminary analysis of platypus ORGs dates the origin of this cluster back to the common ancestor of therian and monotreme mammals more than 166 million years ago, and provides examples of both conservation and adaptation of some genes in this cluster. My general conclusion is that the two distantly related marsupial species have retained very similar genomes since their divergence 70 million years ago. This conservation is reflected both at the level of genome arrangement, and at the organisation and evolution of gene families. This conservation is in marked contrast to the variability observed between eutherian groups, both in gross gene arrangement and in the constitution of the ORG family, suggesting that marsupial genomes have been evolving more slowly than other mammals, possibly due to some unique features of their physiology and way of life. Show more