# Genomics Insights Into High‐Latitude Adaptation of Tibetan Macaques

## TL;DR

Tibetan macaques have evolved shortened tails and increased fat storage to survive in cold, high-latitude regions, with genetic evidence pointing to specific mutations and adaptations.

## Contribution

Discovery of a TBX6 mutation linked to tail morphology and genomic evidence of lipid metabolism adaptations in Tibetan macaques.

## Key findings

- A homozygous Pro71Thr mutation in TBX6 causes reduced caudal vertebrae in Tibetan macaques.
- Genomic evidence shows enhanced lipid metabolism and fat storage adaptations in Tibetan macaques.
- Tibetan macaques have 9.3-fold more abdominal fat than rhesus macaques, aiding thermoregulation.

## Abstract

Few nonhuman primates inhabit high‐latitude regions that pose significant adaptive challenges. The Tibetan macaque (Macaca thibetana) represents a rare primate species entirely distributed north of the Tropic of Cancer. To investigate the genetic basis underlying its adaptation to high latitudes, we generated a refined Tibetan macaque reference genome (99.41% completeness). Genomic analyses identified a species‐specific homozygous mutation (Pro71Thr) in the TBX6 gene, which potentially explains their characteristic shortened tail morphology. Functional validation using CRISPR‐Cas9‐edited mice demonstrated that this mutation reduces caudal vertebrae count, providing a mechanistic basis for the shortened tail. Quantitative CT revealed that Tibetan macaques accumulated approximately 9.3‐fold more abdominal fat than rhesus macaques. Genomic analysis uncovered enhanced lipid metabolic capacity supported by multiple sources of evidence: (1) positive selection on genes associated with lipid storage (DGAT2, DYSF, CAV1), adipogenesis (PRKD1), and appetite regulation (LEPR); (2) a 390‐bp deletion in CPE; (3) expansions of gene families on oxidative phosphorylation and gluconeogenesis/glycolysis. These genetic variations may account for the marked differences in adipose tissue gene expression between the two macaque species. The shortened tail and increased fat accumulation represent key adaptations for thermoregulation and energy conservation in high‐latitude habitats. Notably, all Tibetan macaque populations experienced long‐term selection pressures from cold at high latitudes, which have not only shaped distinctive adaptive traits, but may also render the species particularly vulnerable to contemporary climate warming, particularly for the eastern populations.

Tibetan macaques exhibit unique adaptations to cold, high‐latitude environments, including shortened tails and enhanced fat storage. Genomic analyses reveal a species‐specific TBX6 mutation linked to tail reduction and selection on lipid metabolism genes. These findings illuminate how primates adapt morphologically and physiologically to cold environments, with implications for climate change vulnerability.