Formation of human long intergenic non-coding RNA genes, pseudogenes, and protein genes: Ancestral sequences are key players

Pathways leading to formation of non-coding RNA and protein genes are varied and complex. We report finding a conserved repeat sequence present in human and chimpanzee genomes that appears to have originated from a common primate ancestor. This sequence is repeatedly copied in human chromosome 22 (chr22) low copy repeats (LCR22) or segmental duplications and forms twenty-one different genes, which include the human long intergenic non-coding RNA (lincRNA) family FAM230, a newly discovered lincRNA gene family termed conserved long intergenic non-coding RNAs (clincRNA), pseudogene families, as well as the gamma-glutamyltransferase (GGT) protein gene family and the RNA pseudogenes that originate from GGT sequences. Of particular interest are the GGT5 and USP18 protein genes that appear to have formed from an homologous repeat sequence that also forms the clincRNA gene family. The data point to ancestral DNA sequences, conserved through evolution and duplicated in humans by chromosomal repeat sequences that may serve as functional genomic elements in the development of diverse genes.非编码RNA与蛋白质编码基因的形成通路多样且复杂。本研究报道了在人类与黑猩猩基因组中发现的一类保守重复序列（conserved repeat sequence），该序列似乎起源于共同的灵长类祖先。该序列在人类22号染色体（chr22）的低拷贝重复序列（LCR22）或称片段重复区域中发生多次拷贝，并形成21种不同的基因，其中涵盖人类基因间长链非编码RNA（long intergenic non-coding RNA，lincRNA）家族FAM230、一类新发现的被命名为保守型基因间长链非编码RNA（conserved long intergenic non-coding RNAs，clincRNA）的基因家族、假基因家族，以及γ-谷氨酰转移酶（gamma-glutamyltransferase，GGT）蛋白质编码基因家族和源自GGT序列的RNA假基因。尤为值得关注的是GGT5与USP18蛋白质编码基因，它们似乎由一类同源重复序列演化而来，而该序列同时也是clincRNA基因家族的构成基础。本研究数据表明，经演化保守并通过染色体重复序列在人类体内发生复制的祖先DNA序列，可作为功能性基因组元件参与多样化基因的发育过程。