Elephant shark sequence reveals unique insights into the evolutionary history of vertebrate genes: A comparative analysis of the protocadherin cluster

Abstract

Cartilaginous fishes are the oldest living phylogenetic group of jawed vertebrates. Here, we demonstrate the value of cartilaginous fish sequences in reconstructing the evolutionary history of vertebrate genomes by sequencing the protocadherin cluster in the relatively small genome (910 Mb) of the elephant shark (Callorhinchus milii). Human and coelacanth contain a single protocadherin cluster with 53 and 49 genes, respectively, that are organized in three subclusters, Pcdh␣, Pcdh␤, and Pcdh␥, whereas the duplicated protocadherin clusters in fugu and zebrafish contain >77 and 107 genes, respectively, that are organized in Pcdh␣ and Pcdh␥ subclusters. By contrast, the elephant shark contains a single protocadherin cluster with 47 genes organized in four subclusters (Pcdh␦, Pcdh, Pcdh, and Pcdh). By comparison with elephant shark sequences, we discovered a Pcdh␦ subcluster in teleost fishes, coelacanth, Xenopus, and chicken. Our results suggest that the protocadherin cluster in the ancestral jawed vertebrate contained more subclusters than modern vertebrates, and the evolution of the protocadherin cluster is characterized by lineagespecific differential loss of entire subclusters of genes. In contrast to teleost fish and mammalian protocadherin genes that have undergone gene conversion events, elephant shark protocadherin genes have experienced very little gene conversion. The syntenic block of genes in the elephant shark protocadherin locus is well conserved in human but disrupted in fugu. Thus, the elephant shark genome appears to be less prone to rearrangements compared with teleost fish genomes. The small and ''stable'' genome of the elephant shark is a valuable reference for understanding the evolution of vertebrate genomes.ancestral jawed vertebrate ͉ clustered protocadherins ͉ cartilaginous fish ͉ Callorhinchus milii ͉ gene conversion R econstructing the evolutionary history of vertebrate genomes, and in particular the human genome, is a major goal of vertebrate comparative genomics. Efforts are underway to reconstruct the evolutionary history of the human genome at the nucleotide level and at the level of large-scale chromosomal rearrangements (1) with the objective of predicting ancestral genomes with high accuracy. The accuracy of the reconstruction of ancestral genomes is greatly influenced by the choice and number of genomes compared. Although a comparison of genomes from all major vertebrate groups is desirable, it is also important to compare genomes from the most distant branches of the phylogenetic tree. Here, we show how the genome sequence from the oldest living phylogenetic group of jawed vertebrates, the cartilaginous fishes, can dramatically change our inferences of the state of the ancestral vertebrate genome.The protocadherin gene cluster is one of the most evolutionarily dynamic loci in vertebrates. It is composed of tandem arrays of paralogous genes that are highly susceptible to lineage-specific gene losses, tandem duplications, and gene conversion (2-7). These clustered genes are distinc...

Rapid genome reshaping by multiple-gene loss after whole-genome duplication in teleost fish suggested by mathematical modeling

“…Also, an analysis comparing lengths of coding sequences (SI Text and Fig. S6) indicated that the longer genes, likely containing more protein domains and motifs, are more common among 1to2 than 1to1 orthogroups, as shown in the previous studies (13,25). These analyses also imply that natural selection contributed to retention of some of the paired gene lineages.…”

Rapidly evolving fish genomes and teleost diversity

“…For example, in contrast to the tight linkage between the human genes for the neurohypophysial hormones, oxytocin and vasopressin, and their orthologs in other tetrapods and coelacanth, the fugu and Tetraodon orthologs are separated by several unrelated genes and flanked by nonsyntenic genes [23]. Likewise, most of the genes flanking the duplicated protocadherin clusters in fugu are unrelated to the conserved syntenic genes flanking the unduplicated protocadherin cluster in the elephant shark and human [24 ].…”

“…Moreover, a comparison of gene order across large regions provides support for a higher rate of chromosomal rearrangements in teleost fishes compared to other vertebrates [23,24 ]. For example, in contrast to the tight linkage between the human genes for the neurohypophysial hormones, oxytocin and vasopressin, and their orthologs in other tetrapods and coelacanth, the fugu and Tetraodon orthologs are separated by several unrelated genes and flanked by nonsyntenic genes [23].…”

“…A comparison of syntenic genes in the elephant shark (genes that map to the paired ends of a fosmid clone) with their orthologs in human and zebrafish genomes showed that the level of conserved synteny between the elephant shark and zebrafish is less than half of that between the elephant shark and human, and that the conserved clusters of syntenic genes in zebrafish contain fewer genes than in elephant shark and human [20 ]. Although the loss of conserved synteny in teleosts can be because of the reciprocal loss of paralogous genes in duplicate chromosomes, comparisons of gene maps have indicated a high frequency of intrachromosomal rearrangements since the divergence of teleost and tetrapod ancestors [21,22].Moreover, a comparison of gene order across large regions provides support for a higher rate of chromosomal rearrangements in teleost fishes compared to other vertebrates [23,24 ]. For example, in contrast to the tight linkage between the human genes for the neurohypophysial hormones, oxytocin and vasopressin, and their orthologs in other tetrapods and coelacanth, the fugu and Tetraodon orthologs are separated by several unrelated genes and flanked by nonsyntenic genes [23].…”

Whole Genome Duplications and the Radiation of Vertebrates

“…Its genome contains convincing evidence that the lineage it belongs to experienced two rounds of genome duplication (Venkatesh et al, 2007). Other studies on this species provide further evidence that this lineage has highly conserved features in some genomic regions (Venkatesh et al, 2006;Yu et al, 2008). This conservation suggests that the common ancestor of chondrichthyans and osteichthyans apparently had a genome that was characterized by two consecutive rounds of genome duplications.…”