Conserved Synteny Between the Ciona Genome and Human Paralogons Identifies Large Duplication Events in the Molecular Evolution of the Insulin-Relaxin Gene Family

Abstract

The aims of the study were to outline the sequence of events that gave rise to the vertebrate insulin-relaxin gene family and the chromosomal regions in which they reside. We analyzed the gene content surrounding the human insulin/relaxin genes with respect to what family they belonged to and if the duplication history of investigated families parallels the evolution of the insulin-relaxin family members. Markov Clustering and phylogenetic analysis were used to determine family identity. More than 15% of the genes belonged to families that have paralogs in the regions, defining two sets of quadruplicate paralogy regions. Thereby, the localization of insulin/relaxin genes in humans is in accordance with those regions on human chromosomes 1, 11, 12, 19q (insulin/insulin-like growth factors) and 1, 6p/15q, 9/5, 19p (insulin-like factors/relaxins) were formed during two genome duplications. We compared the human genome with that of Ciona intestinalis, a species that split from the vertebrate lineage before the two suggested genome duplications. Two insulin-like orthologs were discovered in addition to the already described Ci-insulin gene. Conserved synteny between the Ciona regions hosting the insulin-like genes and the two sets of human paralogons implies their common origin. Linkage of the two human paralogons, as seen in human chromosome 1, as well as the two regions hosting the Ciona insulin-like genes suggests that a segmental duplication gave rise to the region prior to the genome doublings. Thus, preserved gene content provides support that genome duplication(s) in addition to segmental and single-gene duplications shaped the genomes of extant vertebrates.

Evolution of the Relaxin/Insulin-like Gene Family in Placental Mammals: Implications for Its Early Evolution

“…In all cases the INSL4 clade is embedded within the RLN1 clade with strong support (Figs. 2, 3), suggesting that this gene arose from an RLN, and not from an INSL ancestor (Bieche et al 2003;Olinski et al 2006b;Wilkinson et al 2005), thus, this phylogeny suggests that the INSL4 gene derives from the duplication of an RLNlike gene that predates the radiation of Euarchontoglires (Fig. 3), and that the gene was secondarily lost in all Euarchontoglires other than catarrhine primates.…”

“…Each of these resulting genes would have been the progenitors of the paralogs found on a given cluster (Fig. 1a, Hsu 2003; Olinski et al 2006b;Park et al 2008a, b). The alternative divergence pre-WGD model would require the duplication of the single RLN/INSL ancestral gene and ensuing differentiation into a proto-RLN and a proto-INSL gene prior to the two rounds of WGDs.…”

“…In the past, different models for the evolution of the RNL/ INSL gene family were developed that made specific predictions regarding genealogical relationships among the different paralogs (Hsu 2003;Olinski et al 2006b;Park et al 2008a, b). However, the most recent phylogenetic studies did not compare the competing evolutionary scenarios in a phylogenetic framework (Good-Avila et al 2009;Park et al 2008a;Wilkinson et al 2005).…”

“…Through the two successive rounds of WGDs, the single-copy proto-RLN/INSL gene would have given rise to three proto-RLN/INSL paralogs, located on three different chromosomes (Fig. 1a, Olinski et al 2006b;Park et al 2008a, b), plus a paralog that was secondarily lost. Subsequent rounds of tandem gene duplication and divergence of each of these three paralogs would eventually give rise to the different clusters found today in extant vertebrates (Hsu 2003;Olinski et b The divergence pre-WGD model.…”

“…1a, Olinski et al 2006b;Park et al 2008a, b), plus a paralog that was secondarily lost. Subsequent rounds of tandem gene duplication and divergence of each of these three paralogs would eventually give rise to the different clusters found today in extant vertebrates (Hsu 2003;Olinski et b The divergence pre-WGD model. In this case, the ancestor of the RLN and INSL genes would have diverged prior to the two rounds of whole genome duplications.…”