Emergence and Evolution of Hominidae-Specific Coding and Noncoding Genomic Sequences.
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.
Department of Biological Sciences, Graduate School of Science, University of Tokyo Division of Population Genetics, National Institute of Genetics, Mishima, Japan.
Morteza Mahmoudi
MM
Saber
Division of Population Genetics, National Institute of Genetics, Mishima, Japan Department of Genetics, School of Life Science, Graduate University for Advanced Studies (SOKENDAI), Mishima, Japan.
Isaac
I
Adeyemi Babarinde
Division of Population Genetics, National Institute of Genetics, Mishima, Japan Department of Genetics, School of Life Science, Graduate University for Advanced Studies (SOKENDAI), Mishima, Japan.
Nilmini
N
Hettiarachchi
Department of Biological Sciences, Graduate School of Science, University of Tokyo Division of Population Genetics, National Institute of Genetics, Mishima, Japan Department of Genetics, School of Life Science, Graduate University for Advanced Studies (SOKENDAI), Mishima, Japan saitounr@nig.ac.jp.
Naruya
N
Saitou
D000818:Animals; D017124:Conserved Sequence; D003579:Cytochrome Reductases / Q000235:genetics; D019143:Evolution, Molecular; D015894:Genome, Human; D015186:Hominidae / Q000235:genetics*; D006801:Humans; D016366:Open Reading Frames; D050862:Oxidoreductases Acting on Sulfur Group Donors; D011110:Polymorphism, Genetic; D011257:Pregnancy Proteins / Q000235:genetics; D062085:RNA, Long Noncoding; D012045:Regulatory Sequences, Nucleic Acid; D012641:Selection, Genetic
C110524:DSCR4 lncRNA, human; D011257:Pregnancy Proteins; D062085:RNA, Long Noncoding; D003579:Cytochrome Reductases; C500897:GFER protein, human; D050862:Oxidoreductases Acting on Sulfur Group Donors
DSCR4; Hominidae; accelerated evolution; conserved noncoding sequences; lineage-specific genes