The coming adventure of SCML1

This is interesting:

SCML1 has 16 substitutions (of which 15 are nonsynonymous) and zero polymorphisms. Such a pattern is consistent with repeated selective sweeps driving divergence between species, while eliminating variation within species. SCML1 is a repressor of expression of Hox genes and may play an important role in the control of embryonal development [43]. This gene may be a prime candidate for explaining developmental differences between humans and chimpanzees (Nielsen et al. 2005:e170).

What is this SCML1? OMIM reviews the paper by Van de Vosse et al. (1998) that characterized the gene:

The Drosophila Polycomb group (PcG) of genes, which includes the 'sex comb on midleg' (Scm) gene, encodes transcriptional repressors that are involved in the regulation of homeotic genes. Similarly, mammalian homologs of the PcG appear to be involved in the transcriptional repression of HOX genes (see 142950), the vertebrate counterparts of the homeotic genes. Using exon trapping on a contig from Xp22, van de Vosse et al. (1998) identified a novel gene with significant sequence similarity to Scm. They therefore named the gene SCM-like-1 (SCML1). The SCML1 gene spans 18 kb and contains 6 exons. It is transcribed from telomere to centromere. Northern blot analysis detected a major approximately 3-kb SCML1 transcript in all human adult and fetal tissues tested, with the highest expression in adult skeletal muscle and heart and fetal liver. The predicted 208-amino acid SCML1 protein contains 2 domains that are present in PcG gene products and their mammalian homologs. In addition to the Scm gene product, the SCML1 protein shares high sequence similarity with the Drosophila polyhomeotic (Ph) gene product, mouse Mph1, and human EDR1 (602978) and EDR2 (602979), all of which are PcG members or homologs. The authors identified cDNAs representing alternatively spliced SCML1 transcripts.

What a great example of how geneticists figure things out. Here's a Drosophila gene that acts as a repressor for homeotic genes, and thereby is very important to development. Geneticists found a homolog of the gene in humans (they have since found at least one more, SCML2). They tested where the gene is transcribed. Later, genomic surveys of variation found good evidence for recurrent selection in the gene in the human lineage.

We still don't know what it does, or why it was selected. That's the adventure part.

References:

Nielsen R et al. 2005. A Scan for Positively Selected Genes in the Genomes of Humans and Chimpanzees. PLoS Biol 3:e170. Full text (free)

van de Vosse, E.; Walpole, S. M.; Nicolaou, A.; van der Bent, P.; Cahn, A.; Vaudin, M.; Ross, M. T.; Durham, J.; Pavitt, R.; Wilkinson, J.; Grafham, D.; Bergen, A. A. B.; van Ommen, G.-J. B.; Yates, J. R. W.; den Dunnen, J. T.; Trump, D. 1998. Characterization of SCML1, a new gene in Xp22, with homology to developmental polycomb genes. Genomics 49: 96-102.