Overlapping of MINK and CHRNE gene loci in the course of mammalian evolution

Abstract

Overlapping of genes, especially in an anti-parallel fashion, is quite rare in eukaryotic genomes. We have found a rare instance of exon overlapping involving CHRNE and MINK gene loci on chromosome 17 in humans. CHRNE codes for the epsilon subunit of the nicotinic acetylcholine receptor (AChRepsilon) whereas MINK encodes a serine/threonine kinase belonging to the GCK family. To elucidate the evolutionary trail of this gene overlapping event, we examined the genomes of a number of primates and found that mutations in the polyadenylation signal of the CHRNE gene in early hominoids led to the overlap. Upon extending this analysis to genomes of other orders of placental mammals, we observed that the overlapping occurred at least three times independently during the course of mammalian evolution. Because CHRNE and MINK are differentially expressed, the potentially hazardous mutations responsible for the exon overlap seem to have escaped evolutionary pressures by differential temporo-spatial expression of the two genes.

Figure 1

Gene structures of MINK and CHRNE in humans. (A) A schematic showing the location of the BAC clone, hRPK.177_H_5. It is located at Ch17 p13.1, between two markers, D17S1798 at 9.8 cM and D17S938 at 14.8 cM. (B) Gene organisation of MINK and CHRNE loci in the BAC clone shown in (A). Vertical bars represent exons. Arrows indicate the direction of transcription. CHRNE spans ∼6 kb and consists of 11 exons. MINK spans >60 kb and consists of 32 exons. Their last exons exhibit an anti-parallel overlap for 280 bp.

Figure 2

Structure of MINK/CHRNE junctions in various mammalian species and their evolutionary relationship. (A) Structure of the MINK/CHRNE junction in the human genome. Last exons of human MINK and CHRNE genes are shown as rectangles. Coding regions are yellow and 3′ UTRs are white. The stop codon and the functional polyadenylation signal are shown as green and blue vertical stripes, respectively (CHRNE), or as purple and red vertical stripes, respectively (MINK). The three sites that can potentially give rise to polyadenylation signals are indicated by arrows. (B) A schematic showing the MINK/CHRNE junction in various placental mammals. The structure of the MINK/CHRNE junction is represented as in (A). An evolutionary tree based on molecular analyses is shown on the left (–21,27). Each branch is indicated with the name of the order. Other classifications used in the text are shown with ovals. Asterisks represent occurrence of a gene overlapping event within a particular branch of the evolutionary tree.

Figure 3

Comparison of nucleotide sequences around the potential polyadenylation sites for the CHRNE gene. (A) Nucleotide sequences around the potential polyadenylation site 1 for the CHRNE gene are aligned. Shown in blue are the consensus sequences where upper case represents >50% identities and lower case represents <49% identities. Sequences in site 1 are in bold type. Nucleotide sequences that match to the consensus sequences are shown in red while those that do not are in black. (B) Nucleotide sequences around the potential polyadenylation site 2 for the CHRNE gene are aligned in the same manner as in (A).