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Welcome
Wed, 01/02/2008 - 13:21
We focus on comparative analyses of genome sequences to understand principals of molecular evolution and approach the fundamental questions of the origin and evolution of biological complexity. Through analysis of multiple species, we aim to quantify evolutionary processes that shape repertoires of functional genomic elements such as - protein coding genes
- non-coding RNA genes (e.g. microRNAs), and
- conserved non-genic sequences (CNS)
as well as to interrogate and predict their functions, analysing sequence variability patterns among different species and within populations. Prioritising medical and evolutionary questions, we are focusing on two strategic directions of vertebrate and insect genomics, where we are participating in international collaborative projects to analyze the genomes and collaborating with experimental functional genomics laboratories.
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Sequencing the Cow's Genetic Code
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Researchers from the Universities of Geneva and Lausanne, as well as the Swiss Institute of Bioinformatics have been part of a major international project to sequence the bovine (cow) genome, a female Hereford cow named L1 Dominette. Sequencing the bovine genome is now complete, paving the way for research into more sustainable food production, taking into account the needs of an increasing world population. The genome provides a major novel resource to study not only mammalian evolution but also cattle-specific biology, reported an international consortium of researchers in the April 23 issue of the journal Science. A companion study on the genetic bases of mammalian milk is published in parallel.
The large-scale undertaking mobilized more than 300 scientists from 25 countries over six years. The findings of this study provide the means to select animals with a smaller environmental footprint, particularly animals with less greenhouse gas emissions.
“The bovine genome is more similar to that of humans than mice or rats at all levels, from genomic DNA rearrangements, to shared genes and identity of their protein sequences” said Evgeny Zdobnov, one of the lead analysts from the project and a researcher at the University of Geneva and the Swiss Institute of Bioinformatics. He explains that “the finding that about 75% of human genes are well conserved across mammals is striking. The bovine genome gives us further insight into human biology, allowing us to highlight the loss or gain of certain gene families in hominoids. For example, humans have lost a large number of genes which encode the receptors that recognize molecules surrounding a cell and activate the necessary answers."
The research conducted by the teams of Professor Alexandre Reymond at UNIL and Professors Stylianos E. Antonarakis and Evgeny Zdobnov at UNIGE, has determined that the cow genome is made up of at least 22,000 protein-coding genes and 500 miRNAs, a class of genes that regulates the production of most of these proteins. The majority of the genes in the former group can encode several different proteins through a mechanism called alternative splicing. “The sequencing of the cow genome allowed us to determine that this diversification mechanism is more evolutionary conserved than previously thought”, says Alexandre Reymond, the leader of the analysis.
It appears that chromosomal rearrangements are essential for the acquisition of differences between mammals. In cattle biology, they have an influence on the genes involved in the processes of immunity, lactation, digestion and metabolism. These changes could help explain the amazing ability of cattle to efficiently convert low-quality forage into energy-dense meat and milk, processes long exploited by man.
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Selected recent publications
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The Genome Sequence of Taurine Cattle: A Window to Ruminant Biology and EvolutionThe Bovine Genome Sequencing and Analysis Consortium (incl. Gerlach D, Junier T, Kriventseva EV, Zdobnov EM) Science. 2009 Apr 24;324(5926):522-528 PMID: 19390049 To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
Genome Sequence of Aedes aegypti, a Major Arbovirus VectorNene V, Wortman JR, Lawson D, Haas B, Kodira C, Tu ZJ, Loftus B, Xi Z, Megy K, Grabherr M, Ren Q, Zdobnov EM, Lobo NF, Campbell KS, Brown SE, Bonaldo MF, Zhu J, Sinkins SP, Hogenkamp DG, Amedo P, Arsenburger P, Atkinson PW, Bidwell S, Biedler J, Birney E, Bruggner RV, Costas J, Coy MR, Crabtree J, Crawford M, Debruyn B, Decaprio D, Eiglmeier K, Eisenstadt E, El-Dorry H, Gelbart WM, Gomes SL, Hammond M, Hannick LI, Hogan JR, Holmes MH, Jaffe D, Johnston SJ, Kennedy RC, Koo H, Kravitz S, Kriventseva EV, Kulp D, Labutti K, Lee E, Li S, Lovin DD, Mao C, Mauceli E, Menck CF, Miller JR, Montgomery P, Mori A, Nascimento AL, Naveira HF, Nusbaum C, O'leary SB, Orvis J, Pertea M, Quesneville H, Reidenbach KR, Rogers YH, Roth CW, Schneider JR, Schatz M, Shumway M, Stanke M, Stinson EO, Tubio JM, Vanzee JP, Verjovski-Almeida S, Werner D, White O, Wyder S, Zeng Q, Zhao Q, Zhao Y, Hill CA, Raikhel AS, Soares MB, Knudson DL, Lee NH, Galagan J, Salzberg SL, Paulsen IT, Dimopoulos G, Collins FH, Bruce B, Fraser-Liggett CM, Severson DW. Science. 2007 Jun 22;316(5832):1718-23. Epub 2007 May 17. PMID: 17510324 We present a draft sequence of the genome of Aedes aegypti, the primary vector for yellow fever and dengue fever, which at ~1.38 Gbp is ~5-fold larger in size than the genome of the malaria vector, Anopheles gambiae. Nearly 50% of the Aedes aegypti genome consists of transposable elements. These contribute to a ~4-6 fold increase in average gene length and the size of intergenic regions relative to Anopheles gambiae and Drosophila melanogaster. Nevertheless, chromosomal synteny is generally maintained between all three insects although conservation of orthologous gene order is higher (~2-fold) between the mosquito species than between either of them and fruit fly. An increase in genes encoding odorant binding, cytochrome P450 and cuticle domains relative to Anopheles gambiae suggests that members of these protein families underpin some of the biological differences between them.
Evolutionary dynamics of immune-related genes and pathways in disease vector mosquitoesWaterhouse RM, Kriventseva EV, Meister S, Xi Z, Alvarez KS, Bartholomay LC, Carolina Barillas-Mury C, Bian G, Blandin S, Bruce M. Christensen BM, Dong Y, Jiang H, Kanost MR, Koutsos AC, Levashina EA, Li J, Ligoxygakis P, MacCallum RM, Mayhew GF, Mendes A, Michel K, Osta MA, Paskewitz S, Shin SW, Vlachou D, Wang L, Wei W, Zheng L, Zou Z, Severson DW, Raikhel AS, Kafatos FC, Dimopoulos G, Zdobnov EM George K. Christophides GK Science. 2007 Jun 22;316(5832):1738-43. PMID: 17588928 Mosquitoes are vectors of parasitic and viral diseases of immense importance for public health.
The genome sequence of the yellow fever and Dengue vector, Aedes aegypti (Aa), has enabled a
comparative phylogenomic analysis of the insect immune repertoire: in Aa, the malaria vector
Anopheles gambiae (Ag) and the fruitfly Drosophila melanogaster (Dm). Analysis of immune
signaling pathways and response modules reveals both conservative and rapidly evolving features
associated with different functional gene categories and particular aspects of immune reactions.
These dynamics reflect in part continuous readjustment between accommodation and rejection of
pathogens and suggest how innate immunity may have evolved.
Insights into social insects from the genome of the honeybee Apis melliferaHoneybee Genome Sequencing Consortium Nature. 2006 Oct 26;443(7114):931-49 PMID: 17073008 Here we report the genome sequence of the honeybee Apis mellifera, a key model for social behaviour and essential to global ecology through pollination. Compared with other sequenced insect genomes, the A. mellifera genome has high A+T and CpG contents, lacks major transposon families, evolves more slowly, and is more similar to vertebrates for circadian rhythm, RNA interference and DNA methylation genes, among others. Furthermore, A. mellifera has fewer genes for innate immunity, detoxification enzymes, cuticle-forming proteins and gustatory receptors, more genes for odorant receptors, and novel genes for nectar and pollen utilization, consistent with its ecology and social organization. Compared to Drosophila, genes in early developmental pathways differ in Apis, whereas similarities exist for functions that differ markedly, such as sex determination, brain function and behaviour. Population genetics suggests a novel African origin for the species A. mellifera and insights into whether Africanized bees spread throughout the New World via hybridization or displacement.
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