Molecular Biological Study of Chemokine Gene Family

趋化因子是一类在各种类型白细胞定向迁移中起重要作用的小细胞因子家族。根据其半胱氨酸的保守排列，可分为CXC和CC两个主要亚家族和C和CX_3C两个次要亚家族，目前已在人类中鉴定出40多个成员。引人注目的是，大多数CXC趋化因子基因和CC趋化因子基因分别紧密地聚集在染色体4 q12 -21和17q11.2。类似地，小鼠主要CXC和CC趋化因子基因簇分别位于染色体5和11上。为了了解在各自的染色体位点产生大量CXC和CC趋化因子基因的进化过程，我们构建了BAC和YAC重叠群，覆盖人类和小鼠CXC和CC趋化因子基因的主要簇。结果表明，CXC和CC趋化因子基因的组织中的主要集群是非常分歧的两个物种之间的最可能是由于最近的基因重复和重排。我们的研究结果提供了一个重要的洞察力的进化过程中产生的主要趋化因子基因簇，也有价值的信息分配之间的直系同源物人类和小鼠的主要集群趋化因子。

Chemokines are a family of small cytokines that play essential roles in the directed migration of various types of leukocytes. Based on the arrangement of the conserved cysteine residues, they are classified into two major subfamilies, CXC and CC, and two minor subfamilies, C and CX_3C.So far, more than 40 members of this family have been identified in humans. Strikingly, the majority of CXC chemokine genes and that of CC chemokine genes are closely clustered at chromosomes 4q 12-21 and 17q11.2, respectively. Similarly, the mouse major CXC and CC chemokine gene clusters are located on chromosomes 5 and 11, respectively. In order to understand the evolutionary processes that generated large numbers of CXC and CC chemokine genes in the respective chromosomal sites, we have constructed BAC and YAC contigs covering the human and mouse major clusters of CXC and CC chemokine genes. The results reveal that the organizations of CXC and CC chemokine genes in the major clusters are quite diverged between the two species most probably due to very recent gene duplications and rearrangements. Our results provide an important insight into the evolutionary processes that generated the major chemokine gene clusters and also valuable information in assigning the orthologues between human and mouse major cluster chemokines.