Diversification and Functional Evolution of HOX Proteins

Abstract

Gene duplication and divergence is a major contributor to the generation of morphological diversity and the emergence of novel features in vertebrates during evolution. The availability of sequenced genomes has facilitated our understanding of the evolution of genes and regulatory elements. However, progress in understanding conservation and divergence in the function of proteins has been slow and mainly assessed by comparing protein sequences in combination with in vitro analyses. These approaches help to classify proteins into different families and sub-families, such as distinct types of transcription factors, but how protein function varies within a gene family is less well understood. Some studies have explored the functional evolution of closely related proteins and important insights have begun to emerge. In this review, we will provide a general overview of gene duplication and functional divergence and then focus on the functional evolution of HOX proteins to illustrate evolutionary changes underlying diversification and their role in animal evolution.

Keywords: Drosophila; HOX proteins; gene duplication and divergence; mouse; protein evolution.

FIGURE 1

Tree of life and gene complexity: The diagram shows a phylogenetic tree of animals with the approximate total number of genes present in each genome based on sequencing of their representative genomes (Hedges et al., 2015).

FIGURE 2

Phylogenetic tree depicting the position of postulated whole-genome duplication (R) events during vertebrate evolution. The pink ovals indicate the progressive rounds of whole-genome duplication. The number of Hox clusters (C) in the different species is indicated in parentheses.

FIGURE 3

(A) Diagram shows number of Hox genes in different animals indicating expansion of the Hox cluster into alloparalogs. Duplication events in vertebrates generated 4 Hox clusters to create symparalogs, Human genome has 39 Hox genes suggesting loss of some genes (dotted box) during evolution. (B) Possibilities of functional diversification of duplicated genes in the vertebrate genome after duplication. An example of the invertebrate labial gene from Drosophila, duplication in vertebrates and functional diversification of the homologous Hox1 genes (blue text).

FIGURE 4

(A) Protein sequence alignment of hexapeptide (HP), linker (LK), Homeodomain (HD) and CTM region of Drosophila Labial with that of mouse HOX1 paralogs. (B) Distribution of ancestral activity in HOXA1 protein. (C) Alignment of CTM region in arthropod Labial, vertebrate HOXA1 and HOXB1.

FIGURE 5

Alignment of hexapeptide (HP), linker (LK), homeodomain (HD) and CTM regions from Drosophila (A) and mouse (B) HOX proteins. The three ovel regions on the top of the alignment shows the position of alpha-helices. The ^# sign above the alignment depict amino acids that contact DNA, while star (*) and blue dot under the alignment show conservative and semi conservative amino acids respectively.