8.2% of the Human Genome Is Constrained: Variation in Rates of Turnover across Functional Element Classes in the Human Lineage

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Nearly 99% of the human genome does not encode proteins, and while there recently has been extensive biochemical annotation of the remaining noncoding fraction, it remains unclear whether or not the bulk of these DNA sequences have important functional roles. By comparing the genome sequences of different species we identify genomic regions that have evolved unexpectedly slowly, a signature of natural selection upon functional sequence. Using a high resolution evolutionary approach to find sequence showing evolutionary signatures of functionality we estimate that a total of 8.2% (7.1–9.2%) of the human genome is presently functional, more than three times as much than is functional and shared between human and mouse. This implies that there is an abundance of sequences with short lived lineage-specific functionality. As expected, most of the sequence involved in this functional “turnover” is noncoding, while protein coding sequence is stably preserved over longer evolutionary timescales. More generally, we find that the rate of functional turnover varies significantly across categories of functional noncoding elements. Our results provide a pan-mammalian and whole genome perspective on how rapidly different classes of sequence have gained and lost functionality down the human lineage.

Vyšlo v časopise: 8.2% of the Human Genome Is Constrained: Variation in Rates of Turnover across Functional Element Classes in the Human Lineage. PLoS Genet 10(7): e32767. doi:10.1371/journal.pgen.1004525
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004525

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