RPS4Y gene family evolution in primates

Abstract

Background: The RPS4 gene codifies for ribosomal protein S4, a very well-conserved protein present in all kingdoms. In primates, RPS4 is codified by two functional genes located on both sex chromosomes: the RPS4X and RPS4Y genes. In humans, RPS4Y is duplicated and the Y chromosome therefore carries a third functional paralog: RPS4Y2, which presents a testis-specific expression pattern.

Results: DNA sequence analysis of the intronic and cDNA regions of RPS4Y genes from species covering the entire primate phylogeny showed that the duplication event leading to the second Y-linked copy occurred after the divergence of New World monkeys, about 35 million years ago. Maximum likelihood analyses of the synonymous and non-synonymous substitutions revealed that positive selection was acting on RPS4Y2 gene in the human lineage, which represents the first evidence of positive selection on a ribosomal protein gene. Putative positive amino acid replacements affected the three domains of the protein: one of these changes is located in the KOW protein domain and affects the unique invariable position of this motif, and might thus have a dramatic effect on the protein function.

Conclusion: Here, we shed new light on the evolutionary history of RPS4Y gene family, especially on that of RPS4Y2. The results point that the RPS4Y1 gene might be maintained to compensate gene dosage between sexes, while RPS4Y2 might have acquired a new function, at least in the lineage leading to humans.

Figure 1

Genomic structure of human RPS4 genes. Exonic and intronic lengths and repeat content are shown. Amplified loci on the Y chromosome (regions 1 and 2) and on the pseudogene are shown with arrows.

Figure 2

Neighbor-joining tree with model TVM+G of concatenated region1 and region2 for RPS4Y1 and RPS4Y2 built with PAUP after GBlocks region selection (787 bp). Cja was excluded when performing the analyses since its sequence was too short. Boostrap values (10,000 replicates) are shown on each branch.

Figure 3

Scheme of mammalian RPS4 evolutionary history.

Figure 4

Neighbor-joining tree with model TrNef+G of RPS4X, RPS4Y1, RPS4Y2 cDNAs built with PAUP. Numbers of non-synonymous and synonymous substitutions are shown on each branch. The sequences analyzed were 789 bp long.