Comparative Analysis Among Populations:From A Perspective Of Structural Variations And Loss Genes

Distinct selection pressures,derived by certain living environments and lifestyles,have introduced diversified characteristics to the genomes of different ethnic groups.Here we proposed that the large deletions in the genomes in the normal population is relevant to the adaptive evolution driven by environments.Based on this hypothesis,we explored the correlation between deletions and environmental adaptability of different ethnic groups in the normal population in the context of existing differences among varying ethnicities.Through the comparison of the distribution of genomic deletions among different ethnic groups,we noticed that,among most ethnic groups,the distributions appeared to be very similar,except that of the Jews,which was quite unique,probably caused by the disfavor of interfaith marriage in the Jewish tradition.Intriguingly,the results indicated that the Finnish had a higher frequency of deletions in their genomes,which could be accredited to the fact that they now dwell in the boreal zone and there is no necessity for traits their ancestors required to survive the tropics.Furthermore,we collected the information of loss genes in those deletions,and analyzed how they differed in gene functions and among ethnicities.It was found that except for the Jews,deletions were mostly observed on the Y chromosome.Besides,a majority of loss happened in the protein-coding genes,which indicates that these loss non-coding genes might have more stringent functional constraints,because many of their products participate in the upstream of biological processes,while the protein-coding genes were prone to deletions as there could be functional replacements for their products.Overrepresent Enrichment Analysis(OEA)was performed to assess the functions of all affected genes,and similar pathways were found to be enriched in the Europeans,Latins and South Asians,as reported by previous studies that they do share a closer phylogenetic relationship.Furthermore,we inspected the rates of evolution of certain genes,along with their dispensability,and found that the background mutation rates of the deletion-prone genes were significantly higher(P-value: 0.04)than that of the intact ones,indicating that these deletion-prone genes have weaker functional constraints and are vulnerable to non-synonymous mutations.In addition,NBPF8,an often-deleted gene in the Europeans,was found to have a relatively low expression level in various types of tissues,while the NBPF20 gene,homologous to NBPF8,was highly expressed and remained deletion-free in the European genomes.Thus the function overlap between different genes could be one of the reasons for the gene deletion events.Meanwhile,another deletion-prone gene,NBPF9,for which multiple transcripts were found in the Neanderthal genome,indicated a role of gene deletion in the evolutionary process.