Genomic Analysis Revealed a Convergent Evolution of LINE-1 in Coat Color: A Case Study in Water Buffaloes (Bubalus bubalis)

Abstract

Visible pigmentation phenotypes can be used to explore the regulation of gene expression and the evolution of coat color patterns in animals. Here, we performed whole-genome and RNA sequencing and applied GWAS, comparative population genomics and biological experiments to show that the 2,809 bp long LINE-1 insertion in the ASIP (agouti signaling protein) gene is the causative mutation for the white coat phenotype in swamp buffalo (Bubalus bubalis). This LINE-1 insertion (3’ truncated and containing only 5’ UTR) functions as a strong proximal promoter that leads to a 10-fold increase in the transcription of ASIP in white buffalo skin. The 165 bp of 5’ UTR transcribed from the LINE-1 is spliced into the first coding exon of ASIP, resulting in a chimeric transcript. The increased expression of ASIP prevents melanocyte maturation, leading to the absence of pigment in white buffalo skin and hairs. Phylogenetic analyses indicate that the white buffalo-specific ASIP allele originated from a recent genetic transposition event in swamp buffalo. Interestingly, as a similar LINE-1 insertion has been identified in the cattle ASIP gene, we discuss the convergent mechanism of coat color evolution in the Bovini tribe.

Ruminant-specific retrotransposons shape regulatory evolution of bovine immunity

“…However, the majority of association studies have focused on SNPs, with structural variants only recently gaining attention (Liu et al 2010;Hu et al 2020;Chen et al 2017). Lineage-specific TEs are a prominent source of genomic variation that have been implicated in trait diversity in many domesticated species (Langevin et al 2018;Bannasch et al 2021;Lisch 2013;Wragg et al 2013), but there are currently only a handful of examples of TE insertions affecting ruminant variation, including cholesterol deficiency and coat color (Menzi et al 2016;Liang et al 2021). Our epigenomic approach uncovered TEs as a source of IFNG-inducible enhancers that regulate bovine ISGs, with some that are still polymorphic in modern cattle.…”

“…However, most bovine genomic studies have focused on the effects of single nucleotide variants or small insertions and deletions (Littlejohn et al 2016;Bouwman et al 2018;Xiang et al 2021). Transposable elements (TEs) could potentially have an important role shaping bovine variation and evolution, but with a few exceptions identified by genetic trait mapping (Liang et al 2021;Trigo et al 2021;Girardot et al 2006;Albrecht et al 2012;Schütz et al 2016;Menzi et al 2016), the impact of TEs on bovine biology remain largely unexplored.…”

Coloring inside the lines: genomic architecture and evolution of a widespread color pattern in frogs

“…In doing so, we establish the first evidence of a causal link between ASIP and a color pattern in amphibians. The involvement of ASIP in melanophore differentiation and melanin production has been extensively studied in mammals 28,[35][36][37] , and in rodents in particular [38][39][40] . Vertebral stripe pattern differentiation is likely governed by differential expression of ASIP as alleles differ in non-protein coding regions.…”

“…In multiple organisms, ASIP alleles have evolved rapidly leading to parallel evolution of similar phenotypes within species 42 or groups of closely-related species 28 . In the P. neumanni species complex, species presenting the same color patterns did not share the ASIP alleles with P. robeensis.…”

“…Because all of these SNPs are located outside the predicted protein coding regions, we hypothesize that they affect the expression of the gene. An upregulation of ASIP is linked to lighter phenotypes in mammals 28,29 and fishes 27 , we could thus expect an up-regulation of ASIP in individuals with a wide vertebral stripe.…”