Evolutionary comparative genomics

Lineage-specific novelties: a bottom-up approach

Recently, we developed MANTiS, an application system that:

1. ✓builds a relational database integrating, in a phylogenetic framework, all Ensembl genes, corresponding PANTHER molecular functions and biological processes, as well as GNF, e-genetics, and HMDEG expression data;
   

2. ✓makes extensive use of the Ensembl ortholog/paralog prediction pipeline for identifying gene duplication events; and
   

3. ✓implements a dynamical programming approach for the mapping of gene gains, duplications, and losses on the phylogenetic tree.
   

Through a user-friendly interface, MANTiS allows the user to identify:

1. 1.Gains and losses on specific branches of the tree,
   

2. 2.Genome content of ancestral species,
   

3. 3.Statistically over- or under-represented molecular functions, biological processes and anatomical systems (expression data), and
   

4. 4.Tissue specificity of gained, duplicated, and lost genes. 
   
   

Finally, the entire set of information available in MANTiS can be exploited further using an advanced system of queries by which gene identity, mapping, and function parameters can be combined using logical operators.

Download the MANTiS software at www.mantisdb.org

Using MANTiS (integrating gene duplication inference among 38 metazoan genomes with expression data from 17,503 human genes), we showed that the number of anatomical systems in which genes are expressed decreases steadily with decreased age of the genes’ first appearance in the phylogeny: the oldest genes are expressed, on average, in twice as many anatomical systems than the genes gained recently in evolution. We also show that the rate of increase in gene tissue specificity correlates with the relative rate of increase in the maximum number of cell types in the corresponding taxa.

Figure from Milinkovitch et al. 2010 (Historical Constraints on Vertebrate Genome Evolution); see below for full ref). The number of cell types in existence at the time of appearance of a gene seems to constrain its level of tissue specificity for hundreds of millions of years. Red line (and primary vertical axis): mean number of first-level anatomical systems in which members of human gene families are expressed (16,943 genes, corresponding to 10,302 families, with available eGenetics expression data) as a function of the family’s first appearance in the phylogeny. Blue line (and secondary vertical axis): estimated maximum number of cell types of primitive members of metazoa taxa (indicated with vertical dotted lines). The dashed blue line indicates the gap in available estimates of cell type numbers between early Amniotes and Hominidae. Note that values on the secondary vertical axis are in reverse order.

Selected publications

1. ✓Tzika A. C., Helaers R., Van de Peer Y. & M. C. Milinkovitch
   MANTiS: a phylogenetic framework for multi-species genome comparisons
   Bioinformatics, 24 (2):151-157 (2008)
   

2. Open Access: article
   

3. OpenAccess: supplementary material
   

4. Download the MANTiS software
   

5. ✓Milinkovitch M.C., Helaers R., & A.C. Tzika
   Historical Constraints on Vertebrate Genome Evolution
   Genome Biololgy & Evolution 2010: 13-18 (2010)
   

6. Open Access
   

7. ✓Milinkovitch M.C., Helaers R., Depiereux E., Tzika A.C., & T. Gabaldon
   2X genomes - depth does matter
   Genome Biology, 11 (2): R16 (2010)
   

8. Open Access
   

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