Abstract
A gеnerаl statement/essential background information:
The protective redundancy of paralogous genes partly relies on the fact that they carry their functions independently.
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However, a significant fraction of paralogous proteins may form functionally dependent pairs, for instance, through heteromerization. As a consequence, one could expect these heteromeric paralogs to be less protective against deleterious mutations.
Details of research саrriеd out bу the writеr:
To test this hypothesis, we examined the robustness landscape of gene loss-of-function by CRISPR-Cas9 in more than 450 human cell lines.
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This landscape shows regions of greater deleteriousness to gene inactivation as a function of key paralog properties.
The implementation of аn investigation in а rеаl-wоrld situation:
Heteromeric paralogs are more likely to occupy such regions owing to their high expression and large number of protein–protein interaction partners.
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Further investigation revealed that heteromers may also be under stricter dosage balance, which may also contribute to the higher deleteriousness upon gene inactivation.
The results of the research suggest:
Finally, we suggest that physical dependency may contribute to the deleteriousness upon loss-offunction as revealed by the correlation between the strength of interactions between paralogs and their higher deleteriousness upon loss of function.
Однако значительная часть паралогичных белков может образовывать функционально зависимые пары, например, посредством гетеромеризации.
Как следствие, можно ожидать, что эти гетеромерные паралоги будут менее защищены от вредных мутаций.
Этот ландшафт показывает области большей вредоносности для инактивации генов в зависимости от ключевых свойств паралога.
Гетеромерные паралоги с большей вероятностью занимают такие регионы из-за их высокой экспрессии и большого количества партнеров по межбелковым взаимодействиям.
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