Eric H Lyons
Publications
Abstract:
From the set of all pairwise homologies, weighted by sequence similarities, among a set of genomes, we seek disjoint orthology sets of genes, in which each element is orthogonal to all other genes (on a different genome) in the same set. In a graph-theoretical formulation, where genes are vertices and weighted edges represent homologies, we suggest three criteria, with three different biological motivations, for evaluating the partition of genes produced by deletion of a subset of edges: i) minimum weight edge removal, ii) minimum degree-zero vertex creation, and iii) maximum number of edges in the transitive closure of the graph after edge deletion. For each of the problems, all either proved or conjectured to be NP-hard, we suggest approximate and heuristic algorithms of finding orthology sets satisfying the criteria, and show how to incorporate genomes that have a whole genome duplication event in their immediate lineage. We apply this to ten flowering plant genomes, involving 160,000 different genes in given pairwise homologies. We evaluate the results in a number of ways and recommend criterion iii) as best suited to applications to multiple gene order alignment. © 2011 Springer-Verlag.
Abstract:
Previous work in Arabidopsis showed that after an ancient tetraploidy event, genes were preferentially removed from one of the two homeologs, a process known as fractionation. The mechanism of fractionation is unknown. We sought to determine whether such preferential, or biased, fractionation exists in maize and, if so, whether a specific mechanism could be implicated in this process. We studied the process of fractionation using two recently sequenced grass species: sorghum and maize. The maize lineage has experienced a tetraploidy since its divergence from sorghum approximately 12 million years ago, and fragments of many knocked-out genes retain enough sequence similarity to be easily identifiable. Using sorghum exons as the query sequence, we studied the fate of both orthologous genes in maize following the maize tetraploidy. We show that genes are predominantly lost, not relocated, and that single-gene loss by deletion is the rule. Based on comparisons with orthologous sorghum and rice genes, we also infer that the sequences present before the deletion events were flanked by short direct repeats, a signature of intra-chromosomal recombination. Evidence of this deletion mechanism is found 2.3 times more frequently on one of the maize homeologs, consistent with earlier observations of biased fractionation. The over-fractionated homeolog is also a greater than 3-fold better target for transposon removal, but does not have an observably higher synonymous base substitution rate, nor could we find differentially placed methylation domains. We conclude that fractionation is indeed biased in maize and that intra-chromosomal or possibly a similar illegitimate recombination is the primary mechanism by which fractionation occurs. The mechanism of intra-chromosomal recombination explains the observed bias in both gene and transposon loss in the maize lineage. The existence of fractionation bias demonstrates that the frequency of deletion is modulated. Among the evolutionary benefits of this deletion/fractionation mechanism is bulk DNA removal and the generation of novel combinations of regulatory sequences and coding regions. © 2010 Woodhouse et al.