Genomic Discovery of a Pathway Influencing Adaptation to Temperature Stress in Cattle

A de novo mutation in Halcyon, a Holstein bull was discovered in New Zealand in daughters of him and his son (Matrix).  The mutation resulted in dominant expression of a hairy phenotype in about half the offspring.  The hairy offspring sought out water for wallowing and suffered from heat stress in climatic conditions that would normally be considered to be within the thermo-neutral zone.  Hairy daughters achieved normal pregnancy rates but at least 1/4 did not lactate and those that did produced lower milk yields than their wild-type sisters.  The mutation mapped to PRL known to be involved in mammary gland development and initiation of lactation.  A non-synonymous mutation in exon 5 that was novel to affected individuals was found, and predicted to interfere with one of three disuplhide bonds in the prolactin hormone.  The cause of the heat stress was not the hairy phenotype, as hairy animals clipped to have slick hair coats demonstrated similarly elevated respiration rates and rectal temperatures as their unclipped hairy sisters.  The mutant cows demonstrated much lower sweating rates at 28C than their wild-type sisters.  Comparative genomic analyses of yak and bison that are hairy and adapted to cold environments demonstrated unusual variants, not in PRL but in PRLR.  The QTL responsible for the slick-haired phenotype in heat adapted Senepol cattle had also been mapped to the region including the PRLR gene. Sequencing of Senepol PRLR demonstrated a 1 bp deletion. The prolactin pathway is clearly involved in adaptation to temperature-related climate stress.