Widespread Divergence of the CEACAM/PSG Genes in Vertebrates and Humans Suggests Sensitivity to Selection

Chang, Chia Lin; Semyonov, Jenia; Cheng, Po Jen; Huang, Shang Yu; Park, Jae Il; Tsai, Huai-Jen; Lin, Cheng-Yung; Grützner, Frank; Soong, Yung Kuei; Cai, James J.; Hsu, Sheau Yu Teddy

It is well accepted that frequent gene gain and gene loss in progressive genes could be the result of unequal crossover of genes with repeated domains, which can promote rearrangements through their own repeatability [68, 69] . Similarly, recent studies have shown that CNV mutation rates in duplication-rich regions could be significantly higher than SNPs due to their propensity to undergo nonallelic homologous recombination, thereby making CNV to be recurrent at specific loci [70] . Physiologically, the redundancy of CEACAM/PSG genes could be selected for the provision of a robustness against null phenotypes in individuals [71, 72] . In support of this hypothesis, it has been shown that transgenic mice deficient for Ceacam1, 9, or 10 exhibit minimal or no aberrant phenotypes [3, 73, 74] . In addition, the enhanced redundancy could, theoretically, further reduce the constraint and add new opportunities for genetic drift or selection to operate on new alleles, thereby allowing the accumulation of nonsynonymous SNPs in duplicated PSG genes. However, it is important to note that the presence of repeated sequences alone could not account for the selection of high genetic variations at the CEACAM/PSG locus. Recent studies of CNV hotspots in humans have identified several duplication-rich regions on chromosome 19, which contain clusters of zinc finger proteins (ZNFs, with a total of 204 members on chromosome 19) [75] . However, these ZNF cluster loci did not exhibit appreciable increases of genetic variations as compared to other genes on chromosome 19. For example, the ratio of ZNF family genes that have a high F ST nonsynonymous SNP (5.4%) is similar to that of other genes on the same chromosome (3.2%).