Abstract
BackgroundThe existence of introns in eukaryotic genes is believed to provide an evolutionary advantage by increasing protein diversity through exon shuffling and alternative splicing. However, this eukaryotic feature is associated with the necessity of exclusion of intronic sequences, which requires considerable energy expenditure and can lead to splicing errors. The relationship between intronic burden and evolution is poorly understood. The goal of this study was to analyze the relationship between the intronic burden and the level of evolutionary conservation of the gene.ResultsWe found a positive correlation between the level of evolutionary conservation of a gene and its intronic burden. The level of evolutionary conservation was estimated using the conservation index (CI). The CI value was determined on the basis of the most distant ortholog of the human protein sequence and ranged from 0 (the gene was unique to the human genome) to 9 (an ortholog of the human gene was detected in plants). In multivariable model, both the number of introns and total intron size remained significant predictors of CI. We also found that the number of alternative splice variants was positively correlated with CI.The expression level of a gene was negatively correlated with the number of introns and total size of intronic region. Genes with a greater intronic burden had lower density of missense and nonsense mutations in the coding regions of the gene, which suggests that they are under a stronger pressure from purifying selection.ConclusionsWe identified a positive association between intronic burden and CI. One of the possible explanations of this is the idea of a cost-benefits balance. Evolutionarily conserved (functionally important) genes can “afford” the negative consequences of maintaining multiple introns because these consequences are outweighed by the benefit of maintaining the gene. Evolutionarily conserved and functionally important genes may use introns to create novel splice variants to tune the gene function to developmental stage and tissue type.
Highlights
The existence of introns in eukaryotic genes is believed to provide an evolutionary advantage by increasing protein diversity through exon shuffling and alternative splicing
Using dbSNP data, we found that the number of synonymous single nucleotide polymorphisms (SNPs) per codon did not correlate with conservation index (CI) (R = 0.01, N = 16,194, P = 0.18), whereas the number of non-synonymous SNPs and stopgained SNPs was negatively correlated with CI (R = −0.1, n = 16,194, P < 10−6 and R = −0.06, n = 16,194, P < 10−6, respectively)
Previous research found a positive association between the level of evolutionary conservation and the size of the intronic region of a gene for a fraction of the human genes
Summary
The existence of introns in eukaryotic genes is believed to provide an evolutionary advantage by increasing protein diversity through exon shuffling and alternative splicing. This eukaryotic feature is associated with the necessity of exclusion of intronic sequences, which requires considerable energy expenditure and can lead to splicing errors. The division of genes into introns and exons is a hallmark of eukaryotic evolution. This division is believed to be evolutionarily beneficial because it allows the production of multiple proteins from the same gene through alternative splicing and may accelerate the creation of novel proteins through exon shuffling [1,2,3,4].
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