Runaway GC Evolution in Gerbil Genomes

Abstract

Recombination increases the local GC-content in genomic regions through GC-biased gene conversion (gBGC). The recent discovery of a large genomic region with extreme GC-content in the fat sand rat Psammomys obesus provides a model to study the effects of gBGC on chromosome evolution. Here, we compare the GC-content and GC-to-AT substitution patterns across protein-coding genes of four gerbil species and two murine rodents (mouse and rat). We find that the known high-GC region is present in all the gerbils, and is characterized by high substitution rates for all mutational categories (AT-to-GC, GC-to-AT, and GC-conservative) both at synonymous and nonsynonymous sites. A higher AT-to-GC than GC-to-AT rate is consistent with the high GC-content. Additionally, we find more than 300 genes outside the known region with outlying values of AT-to-GC synonymous substitution rates in gerbils. Of these, over 30% are organized into at least 17 large clusters observable at the megabase-scale. The unusual GC-skewed substitution pattern suggests the evolution of genomic regions with very high recombination rates in the gerbil lineage, which can lead to a runaway increase in GC-content. Our results imply that rapid evolution of GC-content is possible in mammals, with gerbil species providing a powerful model to study the mechanisms of gBGC.

Divergent genes in gerbils: prevalence, relation to GC-biased substitution, and phenotypic relevance

“…Even when we removed the genes located in the extreme high GC region from this analysis, the enrichment is significant (9/40 of divergent proteins in high GC regions, compared to 273/9717 non-divergent proteins; Fisher's Exact Test p-value = 1.5e-06). Using high GC region coordinates previously reported for the Mongolian jird [5], we also found a similar enrichment of aberrantly divergent proteins in GC regions (Fisher's Exact Test; p-value = 9.6e-04) (Additional file 1: Table S2 and Fig. S5).…”

“…It has been shown previously that gerbil genomes have islands of GC bias, and for the Pdx1 gene (located in the island of most extreme GC) this is associated with radical protein sequence divergence [3,5]. To test whether excess mutational change and/or GC bias has driven unusual protein sequence divergence in other gerbil genes, we focused on the 50 genes with aberrantly high relative sequence divergence in sand rats (highest adjusted Sneath value).…”

“…In the case of at least one gene located within a high GC island, Pdx1, these nucleotide changes are associated with unusual amino acid substitutions with potential to adversely impact physiology or development [3,4]. Analysis of transcriptomes from additional species reveal that the 'GC islands' phenomenon is shared between different gerbil species and occurred in the gerbil evolutionary lineage [5].…”

“…What marks gerbil genomes as unusual is the extreme nature of the nucleotide compositional bias, including changes within protein-coding genes. Recent work has revealed that gerbil genomes likely have one large island (~10 Mb) of extreme GC bias, where GC content at synonymous sites reaches almost 100%, and several other less extreme islands on other chromosomes [5]. In eukaryotes, the location of GC-rich domains is often correlated with chromosomal regions of high recombination, such as subtelomeric regions and small chromosomes [8,9].…”

“…In this study, we take a different approach to previous studies that have focused on only one protein, PDX1, or analyzed GC evolution in the gerbil genome [4,5]. First, we focus on the gerbil proteome and we ask how many proteins, besides PDX1, have become 'unusually altered' in amino acid sequence during the evolution of two gerbils: sand rat (Psammomys obesus) and Mongolian jird (Meriones unguiculatus).…”