The Loss of Adipokine Genes in the Chicken Genome and Implications for Insulin Metabolism

Abstract

Gene loss is one of the main drivers in the evolution of genomes and species. The demonstration that a gene has been lost by pseudogenization is truly complete when one finds the pseudogene in the orthologous genomic region with respect to active genes in other species. In some cases, the identification of such orthologous loci is not possible because of chromosomal rearrangements or if the gene of interest has not yet been sequenced. This question is particularly important in the case of birds because the genomes of avian species possess only about 15,000 predicted genes, in comparison with 20,000 in mammals. Yet, gene loss raises the question of which functions are affected by the changes in gene counts. We describe a systematic approach that makes it possible to demonstrate gene loss in the chicken genome even if a pseudogene has not been found. By using phylogenetic and synteny analysis in vertebrates, genome-wide comparisons between the chicken genome and expressed sequence tags, RNAseq data analysis, statistical analysis of the chicken genome, and radiation hybrid mapping, we show that resistin, TNFα, and PAI-1 (SERPINE1), three genes encoding adipokines inhibiting insulin sensitivity, have been lost in chicken and zebra finch genomes. Moreover, omentin, a gene encoding an adipokine that enhances insulin sensitivity, has also been lost in the chicken genome. Overall, only one adipokine inhibiting insulin sensitivity and five adipokines enhancing insulin sensitivity are still present in the chicken genome. These genetic differences between mammals and chicken, given the functions of the genes in mammals, would have dramatic consequences on chicken endocrinology, leading to novel equilibriums especially in the regulation of energy metabolism, insulin sensitivity, as well as appetite and reproduction.

Evolution of the Vertebrate Resistin Gene Family

“…This observation is consistent with a recent report of the loss of adipokine genes, including resistin, from the chicken and zebra finch genomes [24]. A single Retn -like gene was found in the one available amphibian (Class Amphibia) genome ( Xenopus tropicalis ), although it was incomplete as it was located at one end of a short genomic contig (Table 1 and S1 Table).…”

“…Putative RETN orthologs were inferred from the phylogenetic analysis shown in Fig 2 and their flanking genes were identified (Fig 3). As previously reported [24], and shown in Fig 3, many genes near the cow and mouse Retn genes are orthologous to the human genes flanking RETN , with similar results found for several other placental mammalian species that have well assembled genomes (results not shown). The putative opossum Retn ortholog was also found to be in a genomic neighborhood homologous to that of human RETN (Fig 3), demonstrating that the human and opossum Retn genes are indeed orthologous.…”

“…It is also unknown when the Retnl gene family originated. Intriguingly, Retn was lost from the chicken and zebra finch genomes, along with a number of other adipokine genes, which might explain some of the differences in energy metabolism, and its regulation, between birds and mammals [24]. Here we investigated the evolution of Retn and Retnl genes in vertebrates and conclude that Retn is located and the locus of origin for the duplications and that Retnl originated via duplication and transposition to a new genomic location.…”

Decay of sexual trait genes in an asexual parasitoid wasp

“…Ortholog losses appear to be widespread (Wyder et al 2007; Suen et al 2011), although the true absence of a (pseudo)gene is difficult to prove. For example, bird genomes appear to have lost several genes involved in insulin sensitivity, without leaving them as detectable pseudogenes (Dakovic et al 2014). …”

Regulation of the avian central melanocortin system and the role of leptin

“…Birds in particular face very different metabolic challenges from most mammals and from ectothermic vertebrates imposed by the requirements of the intense aerobic activity of flight. Fundamental differences in metabolism such as the relative circulating concentrations of insulin and glucagon, present even in domesticated birds like the chicken, are likely to reflect this and may be linked to the deletion of several adipokine genes from the genome (Dakovic et al, 2014). It would be beneficial for future investigations to draw more on the established metabolic differences between birds and mammals, particularly on the relatively greater reliance in birds on lipid metabolism as a source of metabolic fuels.…”