PRDM9 and the evolution of recombination hotspots

Area of Science:

• Genetics
• Evolutionary Biology
• Population Genetics

Background:

• Recombination hotspots are non-uniformly distributed genomic regions crucial for mammalian genetic diversity.
• Recombination initiates with double-strand breaks, paradoxically leading to hotspot inactivation and potential extinction.
• The Recombination Hotspot Paradox describes the abundance of hotspots despite their self-inactivating nature.

Purpose of the Study:

• To propose an alternative explanation for the Recombination Hotspot Paradox using a population genetics model.
• To investigate the role of PRDM9-like genes and selection in hotspot dynamics.
• To understand the evolutionary persistence and landscape volatility of recombination hotspots.

Main Methods:

• Formulation of a population genetics model incorporating the mammalian recombination initiation mechanism (PRDM9-like genes).
• Analysis of how weak selection influences the inactivation and re-activation (resurrection) of individual recombination hotspots.
• Examination of genomic signatures, specifically selective sweeps, under varying levels of viability selection.

Main Results:

• Weak selection allows individual recombination hotspots to become inactive (die) but prevents their extinction through re-activation (resurrection).
• Rare variants and weak selection cause recombination sites to oscillate between active (hot) and inactive (cold) states.
• Counter-intuitively, lower viability selection results in a harder selective sweep signature at recombination hotspots.

Conclusions:

• The model provides a mechanism for hotspot persistence, reconciling empirical observations with theoretical expectations.
• Weak selection and PRDM9-like gene dynamics explain hotspot resurrection, coexistence of hotspot types, and landscape volatility.
• The findings offer insights into PRDM9 evolution and the low conservation of recombination hotspots between species.