Microinversions in mammalian evolution

Abstract

We propose an approach for identifying microinversions across different species and show that microinversions provide a source of low-homoplasy evolutionary characters. These characters may be used as ''certificates'' to verify different branches in a phylogenetic tree, turning the challenging problem of phylogeny reconstruction into a relatively simple algorithmic problem. We estimate that there exist hundreds of thousands of microinversions in genomes of mammals from comparative sequencing projects, an untapped source of new phylogenetic characters.genome rearrangements ͉ phylogenetics C hromosomal inversions have been used as phylogenetic characters since Dobzhansky and Sturtevant in 1938. Recent comparisons of whole mammalian genomes have revealed a surprisingly large number of microinversions (1, 2). While the microinversions were first met with skepticism and were attributed to assembly errors and alignment artifacts, recent comparative study of human and chimpanzee genomes convincingly proved that microinversions are indeed widespread (3). We therefore decided to perform a fine-grained search for inversions across many mammals in the greater cystic fibrosis transmembrane conductance regulator (CFTR) region. This is a 1.8-megabase region on chromosome 7 in the human genome that encompasses the CFTR gene, and its many neighboring genes, that was sequenced for the ENCyclopedia Of DNA Elements (ENCODE) project (4, 5). We found that microinversions are frequent across all species and occur at roughly one microinversion per megabase per 66 million years of evolution. We show that microinversions have low homoplasy and thus provide ample characters for phylogenetic studies.Our work follows in the steps of the pioneering work by Okada's group (6) and Lake's group (7) that demonstrated the power of repeat-based and deletion-based characters to resolve difficult phylogeny problems that the traditional point mutation analysis failed to resolve. The repeat-based and deletion-based approaches, although very successful, have some drawbacks as reviewed in ref. 8. However, Bashir et al. (9) and Kriegs et al. (10) recently demonstrated that many repeat-based characters may be extracted from genomic sequences to alleviate these drawbacks and to resolve some existing controversies. Our work reveals a source of low-homoplasy phylogenetic characters that complement these previous studies in two respects. First, microinversion homoplasy (if any) may be detected, and such characters can be simply deleted from further consideration without affecting the tree reconstruction algorithm. Second, microinversions may be identified as long as there is a detectable sequence similarity thus not necessarily limiting the comparison to close species as in the case of repeats and deletions. Indeed, Bourque et al. (11) documented many microinversions between human and chicken genomes, whereas Fischer et al. (12) found many microinversions between yeast genomes, which are molecularly as diverse as the genomes of the entire phylum of chord...

A recurrent inversion on the eutherian X chromosome

“…The recent availability of genomic data from multiple species has led to the unexpected discovery that structural variation, including inversions, is relatively common in the human population (3,4), as well as between closely related species, such as human and chimpanzee (5)(6)(7). Comparisons of the positions of evolutionary breakpoints in different mammalian lineages suggest that a small fraction of the mammalian genome is particularly prone to rearrangement and constitute breakpoint ''hotspots'' that have been reused over the course of mammalian evolution (e.g., refs.…”

Breakpoint graphs and ancestral genome reconstructions

“…Each of 32 incorrect partitions (only eight of them are shown in Table 1A) have at most one simple path/cycle and at most six simple multi-edges, an order of magnitude smaller number than non-trivial correct partitions. This observation illustrates that reconstruction of the correct tree topology is a simple exercise in this case (see Chaisson et al 2006). This and other statistics produced by MGRA (see below) may be used to determine the phylogenetic tree rather than to assume that it is given.…”

“…the start and end of a synteny block are not expected to be present in the same (small) connected component unless this block was subject to a ''micro-inversion'' (Chaisson et al 2006). Indeed, blocks 80, 610, 795, 1290, and 1300 turned out to be short (all under 500 kb), with blocks 610, 1290, and 1300 even shorter than 100 kb (block 1300 is 91 kb in human, 41 kb in mouse, and only 10 kb in the dog genome) that is near the threshold of 50 kb used in Ma et al (2006) for generating reliable synteny blocks.…”

“…Similarly to other approaches, the rearrangement analysis reveals some pros and cons for each alternative but does not definitely resolve the long-stranding controversy. Chaisson et al (2006) made an attempt to analyze mammalian phylogeny using micro-rearrangements in the CFTR region representing 0.06% of mammalian genomes. However, the small size of this region and ambiguities in revealing microrearrangements between distant mammals made it difficult to find micro-rearrangements that can certify the deep branches of the mammalian phylogenetic tree.…”

“…First, while the Ma et al (2006) inferCARs algorithm assumes that the phylogeny is known, it remains a subject of enduring debates even in the case of the primate-rodent-carnivore split (which is assumed to be resolved in Ma et al 2006). With the increase in the number of species, the reliability of the phylogeny will become even a bigger concern, thus raising the question of devising an approach that does not assume a fixed phylogeny but instead uses rearrangements as new characters for constructing phylogenetic trees (see Chaisson et al 2006). While MGR does not assume a fixed phylogeny, its heuristically derived weak associations are less reliable.…”