Evolutionary expansion and divergence in the ZNF91 subfamily of primate-specific zinc finger genes

Abstract

Most genes are conserved in mammals, but certain gene families have acquired large numbers of lineage-specific loci through repeated rounds of gene duplication, divergence, and loss that have continued in each mammalian group. One such family encodes KRAB-zinc finger (KRAB-ZNF) proteins, which function as transcriptional repressors. One particular subfamily of KRAB-ZNF genes, including ZNF91, has expanded specifically in primates to comprise more than 110 loci in the human genome. Genes of the ZNF91 subfamily reside in large gene clusters near centromeric regions of human chromosomes 19 and 7 with smaller clusters or isolated copies in other locations. Phylogenetic analysis indicates that many of these genes arose before the split between the New and Old World monkeys, but the ZNF91 subfamily has continued to expand and diversify throughout the evolution of apes and humans. Paralogous loci are distinguished by divergence within their zinc finger arrays, indicating selection for proteins with different regulatory targets. In addition, many loci produce multiple alternatively spliced transcripts encoding proteins that may serve separate and perhaps even opposing regulatory roles because of the modular motif structure of KRAB-ZNF genes. The tissue-specific expression patterns and rapid structural divergence of ZNF91 subfamily genes suggest a role in determining gene expression differences between species and the evolution of novel primate traits.

Gypsy and the Birth of the SCAN Domain

“…Among the genomes we analyzed, the Anolis lizard is the only one with clear host SCAN domains that span the entire length of the retrotransposon RSCAN domain. Though these sequences are closely related to Gmr1 RSCAN sequences, they clearly form a tree with the shorter host SCAN sequences from mammals, most of them are present in the genome closely upstream of tandem ZF sequences, and these putative host SCAN-ZF genes are mostly present in large gene clusters as is typical for tandem ZF genes in mammals (4,9,19). To distinguish these full-length host domains from the shorter SCAN domain and the retroelement RSCAN domain, we refer to them as ESCAN (extended SCAN).…”

Gene inactivation and its implications for annotation in the era of personal genomics

“…It is also difficult to infer ancestral state for some genes and gene families that have undergone human-specific expansion, such as olfactory receptors, defensins, and zinc finger transcription factor genes (Newman and Trask 2003;Schneider et al 2005;Hamilton et al 2006;Groth et al 2010). In some cases, the assignment of ancestral alleles may not be possible, as orthologs may be difficult to identify.…”

Comparative Genomics and Evolution of Alternative Splicing: The Pessimists′ Science

“…113,122 Alternative splicing has a tendency to target regions corresponding to protein functional sites, 111,123 often producing proteins with dominant-negative regulatory effect, numerous examples of which are listed in ref 121. This tendency is particularly interesting in the case of transcription factors, 112,124 producing regulators with different DNAbinding specificities 125,126 or isoforms having overall dominantnegative effect, 121 and in genes encoding protein kinases and phosphatases.…”