Emergence and Evolution of Hominidae-Specific Coding and Noncoding Genomic Sequences

Abstract

Family Hominidae, which includes humans and great apes, is recognized for unique complex social behavior and intellectual abilities. Despite the increasing genome data, however, the genomic origin of its phenotypic uniqueness has remained elusive. Clade-specific genes and highly conserved noncoding sequences (HCNSs) are among the high-potential evolutionary candidates involved in driving clade-specific characters and phenotypes. On this premise, we analyzed whole genome sequences along with gene orthology data retrieved from major DNA databases to find Hominidae-specific (HS) genes and HCNSs. We discovered that Down syndrome critical region 4 (DSCR4) is the only experimentally verified gene uniquely present in Hominidae. DSCR4 has no structural homology to any known protein and was inferred to have emerged in several steps through LTR/ERV1, LTR/ERVL retrotransposition, and transversion. Using the genomic distance as neutral evolution threshold, we identified 1,658 HS HCNSs. Polymorphism coverage and derived allele frequency analysis of HS HCNSs showed that these HCNSs are under purifying selection, indicating that they may harbor important functions. They are overrepresented in promoters/untranslated regions, in close proximity of genes involved in sensory perception of sound and developmental process, and also showed a significantly lower nucleosome occupancy probability. Interestingly, many ancestral sequences of the HS HCNSs showed very high evolutionary rates. This suggests that new functions emerged through some kind of positive selection, and then purifying selection started to operate to keep these functions.

The hominoid-specific gene DSCR4 is involved in regulation of human leukocyte migration

“…2A). DSCR4 has not been under selection constraint between chimpanzee and human (Dn/Ds ratio = 0.996) 14 , however, results of DAF analysis prove that DSCR4 CDSs are under purifying selection in human populations.…”

“…There are multiple biological evidences indicating functionality of the de novo originated protein coding gene, DSCR4 gene such as possessing epigenomic marks for active regulatory region within the promoter, potential secondary structure in DSCR4-coded protein, harboring fetal epigenomic marker for detection of Down syndrome and being the binding site for multiple transcription factors 14 . To verify the functionality of DCSR4 using an evolutionary approach, we also performed Derived Allele Frequency (DAF) analysis.…”

“…Down Syndrome Critical Region 4 (DSCR4) is one of the novel de-novo originated protein coding genes on DSCR region which is present only in humans and great apes and lack orthologous counterpart in 4 non-hominine organisms including mice ( Fig. 1) 14 . This gene, also called as DSCRB 15 share a bidirectional promoter with DSCR8 gene and is positively and negatively regulated by multiple transcription factors [16][17][18] .…”

“…DSCR4 codes an experimentally verified 118 amino acids long protein 19 with strong potentials for forming protein secondary structure 14 , however, this protein shows no significant sign of homology to any know or putative protein domains 14,15 . This lack of homology is expected due to the de novo origin of DSCR4 and considering the fact that majority of three coding exons of this gene is derived from retrotransposons 14 .…”

GC Content Heterogeneity Transition of Conserved Noncoding Sequences Occurred at the Emergence of Vertebrates

“…2004; Lee et al. 2010; Takahashi and Saitou 2012; Babarinde and Saitou 2013; Matsunami and Saitou 2013; Saber et al. 2016) and plant CNSs (Kaplinsky et al.…”